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Retrograde versus antegrade delivery of cardioplegic solution in myocardial revascularization
Retrograde versus antegrade delivery of cardioplegic solution in myocardial revascularization A clinical trial in patients with three-vessel coronary artery disease who underwent myocardial revascularization with extensive use of the internal mammary artery The effects of retrograde and antegrade delivery of cardioplegic solution on myocardial function were evaluated and compared in 60 patients who underwent myocardial revascularization. All patients had three-vessel coronary artery disease, and the revascularization was done with extensive use of the internal mammary artery. Seventy-five percent of the distal anastomoses were performed with the internal mammary artery. Myocardial protection consisted of St. Thomas' Hospital cardioplegic solution, topical slushed ice, and systemic hypothermia (280 C), The patients were randomly separated into two groups: group A (n = 30), who received antegrade cardioplegia, and group B (n = 30), who received retrograde cardioplegia. With the exception of the total dose of cardioplegic solution (p = 0.02), there was no significant difference between the two groups that concerned septal myocardial temperature at the moment of asystole and after infusion of the total dose of cardioplegic solution. Cardiac function was assessed before and after the patient was weaned from cardiopulmonary bypass. In the immediate postoperative period there was a significant increase in right atrial pressure of the patients who underwent antegrade cardioplegia. For the other registered parameters there was no significant difference either in the immediate postoperative period or 6 hours later. Release of creatine kinase MB isoenzyme was the same in the two groups. Clinical outcome in terms of mortality, prevalence of perioperative infarction, prevalence of low cardiac output, and rhythm and conduction disturbances was similar in both groups. Technical problems related to cannulation and decannulation of the coronary sinus were not encountered. Multivariate analysis showed that occlusion of the left anterior descending coronary artery (p = 0.012) is an essential contraindication of antegrade delivery of cardioplegic solution. Analysis of the patients with an occlusion of the left anterior descending coronary artery who underwent antegrade (n = 9) and retrograde (n = 10) cardioplegia showed a significant difference in the total dose of cardioplegic solution (p = 0.02) and septal myocardial temperature at the moment of asystole (p = 0.008) and after infusion of the total dose of cardioplegic solution (p = 0.015). The mean arterial systolic blood pressure in the antegrade group was significantly lower than in the retrograde group (p = 0.003). Preservation of the left ventricular stroke work index was significantly better in the retrograde group (namely, 85 % of its initial value versus 71 % in the
L. Noyez, MD,a Jacques A. M. van Son, MD, phD,a> T. van der Werf, MD,b J. T. A. Knape, MD,c J. Gimbrere, MD,d W. N. J. C. van Asten, PhD,a L. K. Lacquet, MD,a and W. Flameng, MD,e Nijmegen, The Netherlands, and Leuven, Belgium
From the Departments of Thoracic and Cardiac Surgery," Cardiology, b Anesthesiology," Intensive Care," University Hospital Nijmegen St. Radboud, Nijmegen, The Netherlands, and the Department of Cardiac Surgery" of the University Hospital of Leuven, Belgium. Address for reprints: L. Noyez, MD, Department of Thoracic and Cardiac Surgery, University Hospital Nijmegen St. Radboud, Postbus 9101,6500 HB Nijmegen, The Netherlands.
854
Received for publication July 23, 1991. Accepted for publication May 26, 1992. 'Current address: Division of Thoracic and Cardiovascular Surgery, Mayo Clinic, Rochester, Minn.
J
THORAC CARDIOVASC SURG
Copyright
@
1993;105:854-63
1993 by Mosby-Year Book, Inc.
0022-5223/93 $1.00 +.10
12/1/42475
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antegrade group, p = 0.0116). We conclude that retrograde cardioplegia provides better myocardial protection than antegrade cardioplegia in patients with three-vessel coronary artery disease and occlusion of the left anterior descending coronary artery who undergo myocardial revascularization with extensive use of the internal mammary artery. We also conclude that occlusion of the left anterior descending coronary artery is an essential parameter in the inhomogeneous distribution of antegrade cardioplegia. (J THORAC CARDIOVASC SURG 1993;105:854-63)
Adequate distribution of cardioplegic solution in the myocardium and adaptable strategies for its delivery in various clinical situations are two prerequisites for optimal myocardial protection, as described by Buckberg and Rosenkranz.' Currently there is an increasing interest in retrograde cardioplegia in aorta-coronary bypass surgical intervention because of inhomogeneous distribution of cardioplegic solution during antegrade cardioplegia delivery as a result of coronary artery stenosis and use of the internal mammary artery as graft of choice, which prohibits antegrade delivery of cardioplegic solution.' In experimental studies there is evidence of superior myocardial protection of the left ventricle with the use of retrograde cardioplegia, even with patent coronary arteries, but there is less favorable protection of the right ventricle.3• 4 Clinical studies concerning retrograde cardioplegia, however, are few and inconclusive."? This report is a prospective, randomized, clinical trial studying the effect on myocardial performance of antegrade and retrograde cardioplegia in patients with three-vessel coronary artery disease, who underwent aorta-coronary bypass surgical intervention with extensive use of the internal mammary artery. Because the most extreme situation of coronary artery disease is an occlusion, which prohibits antegrade delivery of cardioplegic solution, special attention was given to patients with an occluded left anterior descending coronary artery (LAD).
Patients and methods Patient population. We studied 60 patients who underwent aorta-coronary bypass surgical intervention. All patients had three-vessel coronary artery disease. Exclusion criteria for the study included the following: reoperations, combined procedures, poor left ventricular function (with ejection fraction <0.30) and emergency aorta-coronary bypass grafting (with evolving myocardial infarction, ischemia that is unresponsive to medical therapy, and cardiogenic shock). The patients were randomly separated into two groups: group A tn = 30) received antegrade cardioplegia, and group B (n = 30) received retrograde cardioplegia.Ethical approval and informed consent were obtained. TableI shows the preoperative data. Obesity was defined as more than 100/0 excess body weight; diabetes, as positive results onglucose tolerance test, use of oral antidiabetic medication, or insulin dependency; hypertension, as a systolic blood pressure of
more than 160 mm Hg or a diastolic pressure of more than 100 mm Hg; hyperlipidemia, as a cholesterol level of more than 6.4 mrnol/L or a triglyceride level of more than 2 mmol/L, All previous medication, such as nitrates, Ca++ -entry blockers, and beta-blockers. was continued until midnight before the operation. Surgical technique. A standardized anesthetic technique was used, with intravenous doses of fentanyl citrate (60 Ilg/kg) for anesthesia, pancuronium (0.1 mg /kg) for muscle relaxation, and midazolam (0.07 to 0.1 mg/kg per minute) for amnesia. A Swan-Ganz catheter (Baxter Healthcare Corp., Edwards Division, Irvine, Calif.) was introduced into the pulmonary artery via the internal jugular vein. All operations were performed by one surgeon (L N.) to avoid the variability that would have arisen with multiple surgeons. The distal anastomoses were performed during a single period of crossclamping, and proximal anastomoses were performed with a partial occluding clamp. Standard bypass techniques were used with a Cobe C.M.L-Excel and Maxima membrane oxygenator and a roller pump (Cobe BCT, Inc., Lakewood, Colo.) while the patient underwent systemic hypothermia (with a rectal temperature of 28° C), and moderate hemodilution. Myocardial protection was achieved by infusion of cold (4° C) St. Thomas' Hospital cardioplegic solution (300 ml/rn"), until asystole occurred; protection was maintained by reinfusion of I00 ml of solution per square meter every 25 to 30 minutes, or as often as needed. In group A, the cardioplegic solution was infused in the aortic root with a pressure of ± 100 mm Hg,8 and, in group B, we performed retrograde delivery of cardioplegic solution. In both groups, an additional dose of 25 ml of cardioplegic solution was infused through the venous grafts that were constructed first. The coronary sinus was cannulated transatrially, as described by Gundry and associates.P We used a Gundry RSCP cannula with obturator (DLP, Inc., Grand Rapids, Mich.) or a Buckberg cannula (Research Medical, Inc., Salt Lake City, Utah). Coronary sinus pressure never exceeded 50 mm Hg. In all patients, a left ventricular vent was placed through the right superior pulmonary vein. Patienttemperature was kept between 26° and 28° C, and slushed ice was used as topical cooling. Myocardial septal temperatures were recorded at the moment of asystole and after infusion of the total dose of cardioplegic solution. Before the patient was weaned from extracorporeal circulation, rewarming was done until rectal temperature reached 35° C, and the hematocrit value was increased to a minimum of 24%. Intravenous fluid therapy was intended to achieve optimal filling pressures for the actual myocardial performance, which was monitored by frequent determinations of cardiac filling pressures and calculations of stroke work index and cardiac index. The aorta was decannulated after 5 minutes of hemodynamic stability after cessation of cardiopulmonary bypass.
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Table II. Intraoperative patient data
Table I. Preoperative patient data
No. Male/female Age (yr) BSA (m'') NYHA Obesity Hypertension Diabetes Hyperlipidemia LAD occlusion
Group A
Group B
30 23/7 57.3 ± 8.1 (34-69) 1.94 ± 0.15 (1.6-2.1) 3.1 ± 0.59 (2-4) 8 13 5 10 9
30 25/5 56.1 ± 8.1 (37-69) 1.88 ± 0.10 (1.6-2.4) 3.1 ± 0.5 (2-4) 6 14 3 12 10
p Value NS NS NS NS NS NS NS NS NS
Group data are expressed as mean ± standard deviation. NS, Not significant; BSA, body surface area; NYHA, New York Heart Association classification. Indexes for evaluation of myocardial protection. We assessed recovery of cardiac function in all patients by monitoring systolic (SAP), diastolic (DAP), mean arterial (MAP) blood pressure, mean right atrial pressure (RAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and heart rate (HR). Cardiac output (Q) was measured with the thermodilution technique. Derived hemodynamic indexes were calculated as follows: Cardiac index (QO = Q/Bodysurfacearea (Lyrninper square meter); Stroke index (SO = QI/HR (nil/min per square meter); Left ventricular stroke work index (L VSWI) = SI(MAP PCWP) . 0.0136 (gm/rnin per square meter); Right ventricular stroke work index (RVSWI) = SI(PAP - RAP) . 0.0136 (gm/rnin per square meter); Systemic vascular resistance index (SVRI) = (MAP - RAP)/Q . 80 (dyne. sec . cm"). These hemodynamic variables were measured (I) after induction of anesthesia, (2) after cessation of cardiopulmonary bypass, after a duration of 5 minutes of hemodynamic stability, just before administration of protamine hydrochloride (this registration is further noted as "5 minutes after cessation of cardiopulmonary bypass"), and (3) 6 hours after the operation, in the intensive care unit. At I, 3,6, 12, and 24 hours after the operation, venous blood samples were taken for determination of creatine kinase isoenzyme (CK-MB). Clinical outcome. Intraoperative myocardial infarction was defined as the development of a new Q wave or a concentration of CK-MB of at least 10% or both. Low cardiac output was defined as the need for inotropic support in which dopamine requirements increased 4 ,ug/kg per minute for at least 12 hours or a cardiac index less than 2.2 L/min per square meter. Preoperative and postoperative electrocardiograms were compared, and special attention was given to the appearance of atrioventricular conduction disturbances. There was special attention for problems caused by cannulation and decannulation of the coronary sinus. Statistical analysis. Quantitative data were analyzed with a paired Student t test or a Wilcoxon test when appropriate, and a multivariate analysis was performed. A p value of less than 0.05 indicated that the difference was unlikely to be due to chance alone. Data were expressed as mean values ± standard deviation.
Group A
GroupB
No. 30 30 Cardioplegic solution (ml) 913.3 ± 131.6 1108 ± 204.6 Asystole time (sec) 57.5 ± 27.5 74.2 ± 26.9 (28-148) (32-121 ) Asystole temp (0 C) 20.8 ± 2.3 18.3 ± 2.3 (17-24) (18-22) Myocard temp (0 C) 16.4±3.1 14.9 ± 2.8 (12-19) (12-18) Bypass time (min) 120.1 ± 28.4 127.8 ± 25.7 (78-165) (65-165) Crossclamp time (min) 80.2 ± 13.8 79.1 ± 10.6 (48-98) (63-98) No. of grafts 3.1 ± 0.3 3.2 ± 0.4 (3-4) (3-5) Distal anastomoses (No.) 5.2 ± 1.1 4.6 ± I (4-7) (4-7) Dista1lMA-anast (No.) 3.5 ± 0.5 3.3 ± 0.6 (3-4) (2-5)
p Value p = 0.Q2
NS NS NS NS NS NS NS NS
Group data are expressed as mean ± standard deviation. NS. Notsignificant; Asystole time, time to reach asystole; Asystole temp. septal temperature at the moment ofasystole; Myocard temp, septal temperature after infusion ofthe initial dose ofcardioplegic solution; Distal I MA-anast, distal anastomoses performed with theinternal mammary artery.
Results The intraoperative data are shown in Table II. The mean time to reach asystole in group B was longer than in group A, but the difference did not reach statistical significance. Septal temperature at the moment of asystole and after infusion of the initial dose of cardioplegic solution were not significantly different between the two groups. The total doses of cardioplegic solution were significantly higher in group B; however, the postbypass hematocrit values were comparable for both groups (group A, 26% ± I %; group B, 26% ± 2%). In all patients at least one internal mammary artery was used as graft, either single or sequential, with bilateral use of the internal mammary artery in 80% of the patients. Of the distal anastomoses, 75% were done with the internal mammary artery. The recovery of hemodynamics is summarized in Table III. There was no significant difference in the prebypass values between groups A and B. Comparing the prebypass values with those obtained 5 minutes after cessation of cardiopulmonary bypass, we observed an increase of heart rate, pulmonary artery pressure, pulmonary capillary wedge pressure and a decrease of mean arterial pressure, L VSWI, and R VSWI, which were not statistically significant. Right atrial pressure increased significantly (p < 0.001) in the patients who underwent antegrade cardioplegia and decreased, not significantly, in patients who underwent retrograde cardioplegia. In the two
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Table III. Hemodynamic patient data A No. HR (beats/min) MAP(mm Hg) RAP (mm Hg) PAP(mm Hg) PCWP (mm Hg) Q (Lzrnin) QI (Lyrnin per square meter) SI (rnl/rnin per square meter) LVSWI (gm/rnin per square meter) RVSWI (gm/rnin per square meter) SVRI (dyne. sec· cm- s)
30
61.5 ± 79.4 ± 7.6 ± 17.6 ± 9.9 ± 4.8 ± 2.5 ± 40.4 ± 36.9 ± 6.0 ± 1985 ±
AI
B
BI
A2
B2
83.2 ± 9.1 86.0 ± 8.9 8.2 ± 2.3 17.l±4.1 10.2 ± 4.4 5.3 ± 1.3 2.7 ± 0.3 32.2 ± 4.7 35.5±10.1 4.6 ± 1.8 1830 ± 690
84.1 ± ILl 88.3 ± 9.2 7.1 ± 1.7 17.3 ± 4.2 8.8 ± 2.0 5.3 ± 1.1 2.6 ± 0.8 33.1 ± 9.3 34.7 ± 9.2 4.8 ± 1.4 1880±735
30
7.1 10.2 1.8 4.4 3.1 1.3
0.9 9.4 8.9 1.1 820
58.9 ± 77.2 ± 7.9 ± 15.8 ± 9.5 ± 4.7 ± 2.5 ± 41.9 ± 38.12 ± 5.6 ± 2080 ±
8.0 8.4 1.2 3.6 3.0 1.1
1.2 6.2 7.7 1.0 790
81.5 ± 69.9 ± 9.3 ± 18.1 ± 11.0 ± 5.8 ± 2.6 ± 39.7 ± 30.5 ± 5.1 ± 1245 ±
10.2 9.0 1.8* 2.2 2.4 1.6 0.6 9.5 7.3 0.6 540*
80.2 ± 73.3 ± 6.4 ± 16.1 ± 9.7 ± 5.5 ± 2.8 ± 37.0 ± 31.7 ± 4.9 ± 1380 ±
11.4 7.2 1.1 3.4 3.3 1.8 0.8 6.5 4.6 0.8 430*
Data are expressed as mean values ± standard deviation A. Data group A after anesthesia-induction; B, data group B after anesthesia-induction; A' and B', data group A and B 5 minutes after cessation of cardiopulmonary bypass; A 1 and B2 , data group A and B 6 hours after operation; HR, heart rate; MAP, mean arterial blood pressure; RAP, mean right atrial pressure; PAP. mean pulmonary artery pressure; pewp, pulmonary capillary wedge pressure; Q, cardiac output; Ql, cardiac index; Sf, stroke index; SVRf, systemic vascular resistance index. *p < 0.05 versus preoperative value.
groups, systemic vascular resistance was significantly decreased after bypass but returned to normal values after 6 hours. For the values that were recorded 6 hours after the operation, there was no statistically significant difference in comparison with the prebypass values. We found that patients with an occlusion of the LAD who underwent antegrade cardioplegia had a higher septaltemperature at the moment of asystole and after infusion of the initial dose of cardioplegia than did other patients. Therefore, myocardial protection in the former may have been worse. To quantify this experience, we compared the difference in the LVSWI before cardiopulmonary bypass and 5 minutes after cessation of cardiopulmonary bypass with the higher septal temperature achieved after infusion of the initial dose of cardioplegic solution (Fig. 1and Fig. 2). The statistical representations of8ofthe 10patients with an occluded LAD who received retrograde cardioplegia are situated in the left lower corner of Fig. 1; the representations of patients with an occlusion of the LAD who received antegrade cardioplegia areessentiallysituated in the right upper corner of Fig. 2.The importance of the LAD occlusion was evaluated bymultivariateanalysis. We found a statistically significant difference in the hemodynamic recovery of the left ventricle 5 minutes after cessation of cardiopulmonary bypass (p = 0.012), depending on the status ofthe LAD. Therefore, weseparated and analyzed the data of patients with an occlusion of the LAD in the antegrade group (n = 9) and in the retrograde group (n = 10). We see that the septal temperature at the moment of asystole (22.6 ± 2.1 0 C versus 19.3 ± 1.1 0 C, P = 0.008) and after infusion of the initial dose of cardioplegic solution (17.2 ± 2.1 C versus 13.5 ± 2.1 C, P = 0.005) was 0
0
significantly higher in the antegrade group. The recovery of the hemodynamics of all patients with an occluded LAD is summarized in Table IV. Before bypass there was no significant difference between mean arterial, pulmonary arterial, or pulmonary capillary wedge pressures of the two groups, but there were significant differences for these values in the immediate postoperative period. In the immediate postoperative period, the patients with an occluded LAD who underwent antegrade cardioplegia showed a significant increase of the mean right atrial pressure, as was the case for the entire antegrade group, whereas the mean arterial pressure decreased significantly (p = 0.0003). In the two groups heart rate increased, but not significantly. In the two groups the systemic vascular resistance was significantly decreased after bypass. In both groups the cardiac index 5 minutes after cessation of bypass was higher than before bypass, but the increase did not reach statistical significance. The LVSWI was significantly different between the two groups (p = 0.04) in the postoperative period, with a decrease in the antegrade and retrograde groups to 71% and 85% of control value, respectively (p = 0.0116). Neither group had a significant change in the RVSWI before and after the operation. In Figs. 3 and 4, filling pressure and stroke work are represented in a classic diagram as proposed by Sarnoff." There was a decrease of LVSWI, with an increase of the wedge pressure, in only 2 of 10 patients who underwent retrograde cardioplegia (Fig. 3). In contrast, 7 of9 patients who underwent antegrade cardioplegia experienced the same course (Fig. 4). Analysis of the data of the patients without occlusion of the LAD did not show a significantly different preservation of the LVSWI between antegrade and retrograde
The Journal of Thoracic and Cardiovascular Surgery May 1993
8 5 8 Noyez et al.
A LVSWI
20
~
15 0
-
10
•i •
0 0
~
-
12
13
14
0
5
• D
o
10
11
•
0 0
-
0
15 °C
o
LAD-occlusion
Q
0 0
16
• 17
18
19
20
No LAD-occlusion
Fig. 1. Plot comparing the differencein LVSWI before bypass and LVSWI 5 minutes after cessation of cardiopulmonary bypass (ilLVSWI) with the septal temperature (0C) reached after infusion of the initial dose of cardio-
plegic solution for each patient who underwent retrograde cardioplegia.
t::..LVSWI
20
• •• • •
0 15
0 10
• • § ~
0
8
6
~
0
o
10
0
0
0
'-'
~
-
8
0 0
17
18
0
4
11
12
•
13
14
LAD-occclusion
15 °C
16
o
19
20
No LAD-occclusion
Fig. 2. Plot comparing the difference in LVSWI before bypass and LVSWI 5 minutes after cessation of cardiopulmonary bypass (fiLVSWI) with the septal temperature (0C) reached after infusion of the initial dose of cardio-
plegic solution for each patient who underwent antegrade cardioplegia.
cardioplegia. The release of the cardiac-specific enzyme CK-MB in group A and group B was not different, nor was it different in the two groups with an occlusion ofthe LAD (Fig. 5). In all patients, the clinical outcome was excellent. There were no deaths and no perioperative infarction. Three patients, two in the retrograde and one
in the antegrade group, showed signs of low cardiac output. These were the same patients who needed positive inotropic support after weaning from bypass. Both before and after the operation, all patients had a regular sinus rhythm. No rhythm disturbances or technical problems related to the delivery of cardioplegic solution were noted.
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LVSWI (gm.m/m 2) 60,--------------------------------, 50 40 30
20 10
O'-------'-------'-------L.----------.J
o
5
*
10
PCWP (rnm Hg)
before bypass
20
15
+ 5 min. after bypass
Fig. 3. Plot representing relationship between LVSWI and pulmonary capillary wedge pressure (peWp) before bypass and 5 minutes after bypassfor each patient who underwent retrograde cardioplegia.
Table IV. Hemodynamic data ofpatients with an occluded LAD Prebypass ACP
RCP
ACP
RCP
9 ± ± ± ± ± ± ± ± ± ± ±
10 57.6 ± 8.7 76.6 ± 6.5 7.6 ± 1.3 15.4 ± 4.4 9.1 ± 3.5 4.7 ± 0.8 2.4 ± 0.6 42.8 ± 7.7 38.9 ± 6.5 5.9 ± 2.6 2135 ± 790
9 ± ± ± ± ±
10 77.0 ± 11.8 75.8 ± 6.7*t 5.5 ± 2.4* 15.3 ± 4.4* 9.6±3.1* 5.4 ± 1.1 2.8 ± 0.6 37.2 ± 6.6 33.3 ± 4.5*t 5.0 ± 1.9 1420 ± 460§
No. HR (beats/min) MAP(mm Hg) RAP (rnm Hg) PAP (mm Hg) PCWP (mm Hg) Q (Lyrnin) QI (Lyrnin per square meter) SI (rnl/rnin per square meter) LVSWI (gm/rnin per square meter) RVSWI (grri/rnin per square meter) SVRI (dyne· sec· cm- s)
5 min after cessation of CPS
60.6 81.6 7.7 18.2 10.7 4.8 2.4 41.1 38.8 6.1 1978
7.6 10.3 2.7 4.9 3.7 1.0 0.6 10.8 10.5 1.8 800
81.4 11.7 II.I§ 65.2 10.7 2.2§ 20.7 2.7 14.0 2.6 6.2 ± 1.3 3.1 ± 0.8 39.9 ± 12.1 27.3 ± 7.6 5.1 ± 1.5 1255±510§
Data are expressed as mean values ± standard deviation. ACP, Antegrade cardioplegia; RCP, retrograde cardioplegia; CPB, cardiopulmonary bypass; H R, heart rate; MAP, mean arterial blood pressure; RAP, mean right atrial pressure; PAP, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; Q. cardiac output; QI, cardiac index; SI, stroke index; SVRI, systemic vascular resistance index. 'p < 0.05 ACP (5 minutes after cessation of cardiopulmonary bypass) versus RCP (5 minutes after cessation of cardiopulmonary bypass). tp < 0.05 difference between ACP (prebypass) and RCP (prebypass) versus difference between ACP (5 minutes after cessation of cardiopulmonary bypass) and RCP (5 minutes after cessation of cardiopulmonary bypass). §p < 0.05 versus prebypass value.
Discussion Critical coronary artery stenoses and occlusions may resultin inhomogeneous distribution of antegradely delivered cardioplegic solution and, consequently, poor local myocardial protection.!" 11 Experimental and clinical studies have shown an increase in myocardial energy needs in these jeopardized areas and a depression of the left ventricular function after reperfusion.U'!" Direct
antegrade graft perfusion can circumvent this limitation of antegrade cardioplegia, but with the increasing use of the internal mammary artery for grafting, this becomes technically imposslble.? In these situations, retrograde administration of cardioplegic solution via the coronary venous system is a valuable alternative strategy. The experimental work of Partington and associates-" and the development of techniques 15 for blind cannulation of
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8 6 0 Noyez et at.
LVSWI (gm.m/m 2)
60,-----------------------------,
50 40 30 20 10 0'------------'----------'-----------'------------' o 5 15 20 10
PCWP (rnrn Hg)
*
before bypass
+ 5 min. after bypass
Fig. 4. Plot representing relationship between LVSWI and pulmonarycapillary wedge pressure (PCWP) before bypass and 5 minutes after bypass for each patient who underwent antegrade cardioplegia.
Fig. 5. Release of CK-MB isoenzyme in the first 24 hours after the operation in patients with an occlusion of the LAD. The data represent mean values ± standard deviation. the coronary sinus have contributed to the renewal of interest in the use of retrograde cardioplegia in myocardial revascularization. In our study, we were unable to show better preservation of left ventricular myocardial function with retrograde cardioplegia for the group as a whole. When there was an occlusion of the LAD, however, the preservation of left ventricular function was significantly better when retrograde cardioplegia was used. With an occlusion of
the LAD, the LVSWI decreased to 85% of the initial value when the patients received retrograde cardioplegia versus 71% of the initial value that was achieved when antegrade cardioplegia was used. In the majority of patients with antegrade cardioplegia a decrease of LVSWI was accompanied by an increase in pulmonary capillary wedge pressure, whereas in most patients with retrograde cardioplegia, the decrease in LVSWI, which was less than that of the antegrade group, was accompa-
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 5
nied by a decrease in pulmonary capillary wedge pressure. This observation suggests a better preservation of left ventricular contractility in patients with retrograde cardioplegia. This conclusion, however, is valid only if pulmonary capillary wedge pressure reflects left ventricular diastolic volume. An increase in pulmonary capillary wedge pressure may also be elicited by impaired relaxation or increased stiffness of the left ventricular myocardium, which effects may be inherent to the technique of antegrade cardioplegia per se. Volume-derived indexes should be studied in the future, for instance, with esophageal echocardiography in the operating room. The observed decrease of the L VSWI is comparable to the decrease in left ventricular myocardial performance that we noticed in our previous clinical trial!" and other studies." 17, 18 The superior preservation of left ventricular function in patients with an LAD occlusion in the retrograde group, as observed in this study, is caused to a certain extent by patient selection and extensive use of the internal mammary artery for bypass grafting. The patient group with total occlusion of the LAD approximates the experimental model of Partington and associates-" in which the LAD was ligated. Previous clinical trials"? were inconclusive concerning the superior myocardial protection achieved with retrograde cardioplegia in patients with coronary artery disease, but in none of these studies was there as extensive coronary artery disease as in our study; also, the internal mammary artery was not used extensively for bypass grafting. Fiore and associates described a mean of 2.9 diseased vessels in their study, and we presume therefore that patients with fewer than three diseased vessels were included. In addition, only 65% of the patients received internal mammary arteries as graft. Guiraudon and associates" do not mention the severity of coronaryartery disease or whether revascularization was donewith the internal mammary artery. The importance of the severity and extent of the coronary artery disease isclearly shown in our study, in which multivariate analysis showed that occlusion of the LAD is an essential variablein the distribution of cardioplegic solution. In our study, it was impossible, with a limited number of patients, to analyze at what degree of coronary artery disease retrograde delivery of cardioplegic solution becomes superior to antegrade. In the study by Diehl and associates,' all patients had isolated three-vessel coronary arterydisease, and the internal mammary artery was used in 80% of the patients. The latter study was flawed, however, because of the fact that each patient received an initialdose of cardioplegic solution through the aortic root. Inour study, cardioplegic solution was delivered through
Noyez et al.
86 I
the vein grafts, and topical slushed ice was used in all patients; although these techniques may have reduced the difference in left ventricular preservation between the antegrade and retrograde groups, they are part of our goal to achieve optimal myocardial protection. Myocardial biopsy samples were not taken in this study, but it has been shown that in patients with threevessel disease and a significant stenosis in the LAD, the preservation of energy-rich phosphates during ischemic cardiac arrest is better with retrograde than with antegrade cardioplegia. 19 It is known that a decrease in energy-rich phosphates is a trigger for the sequence of events that leads to cell death. Better preservation of energy-rich phosphates results in improved tolerance of ischemia and can prevent postischemic myocardial dysfunction, as suggested in a recent experimental study.i" The R VSWI was not statistically different before and after bypass in both groups, which is in contrast with the results of the experimental study of Partington and associates.': 4 in which the RVSWI in dogs was decreased. We hypothesize that the less favorable protection of the right ventricle in dogs, in comparison with humans, may be related to the anatomic difference in venous drainage of the right and left ventricles between both. Anatomic studies in dogs?' have shown that most of the right ventricle and the posterior part of the interventricular septum are not drained by the coronary sinus. In contrast, the cardiac venous drainage in human beings seems to be more balanced.F The equal distribution of the venous system over the human heart is confirmed by excellent cooling of the entire heart by retrograde cold cardioplegia as reported in this and other studies- 6, 23, 24 and by application of radionucIide techniques." Delay in cardiac arrest is described as a major disadvantage of retrograde cardioplegia' In our study, we did not observe a significant difference between the two groups in the time that was needed to reach asystole. This is in contrast with Fiore and associates who reported times of 30 and 75 seconds in the antegrade and retrograde groups, respectively, to achieve electromechanical arrest. Our time to achieve asystole in the retrograde group is comparable; in the antegrade group, our time is much longer, which is certainly related to the more extensive coronary artery disease in our patients. The total doses of cardioplegic solution are significantly higher in patients who underwent retrograde cardioplegia, which is not only related to the capacity of the coronary venous system but also to the facility of delivery of retrograde cardioplegic solution without need for interruption of the operation. The latter quality of retrograde cardioplegia is especially advantageous during the performance
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of sequential anastomoses with the internal mammary artery and during testing for leakage of a side-to-side anastomosis, because the grafted myocardial area remains free from fibrillation. Blind cannulation of the coronary sinus circumvents bicaval cannulation, caval snares, and an atriotomy for visualization of the coronary sinus. There were no problems during cannulation and decannulation of the coronary sinus in our study, but our extensive experience with this technique in previous patients has certainly contributed to the lack of complications. The good clinical outcome in both groups in this study is certainly also related to our patient selection and surgical strategy. We operated on a mainly young population to allow for extensive (bilateral) use of the internal mammary artery as a graft, and we did not consider it ethical to include patients with an ejection fraction of less than 0.30. Patients with evolving myocardial infarction, with myocardial ischemia not responsive to medical therapy, and with cardiogenic shock were excluded because successful myocardial protection and revascularization of an acutely ischemic myocardial region is related to several factors and not only to the anatomic occlusion of a coronary artery. Although the clinical outcome was excellent in both groups of patients, early recovery of left ventricular function was better in patients with an occluded LAD who underwent retrograde cardioplegia. This observation correlates with the experimental results that were obtained by the groups headed by Partington and Buckberg. 3, 4 We conclude that retrograde cardioplegia is superior to antegrade cardioplegia with regard to myocardial protection in patients with three-vessel coronary artery disease including occlusion of the LAD who are subjected to myocardial revascularization with extensive use of the internal mammary artery. In addition, we conclude that occlusion of the LAD is a contraindication for the use of antegrade cardioplegia. REFERENCES I. Buckberg GD. Rosenkranz EL. Principles of cardioplegic myocardial protection. In: Roberts AJ, ed. Myocardial protection in cardiac surgery. New York: Dekker, 1986:7194. 2. Buckberg GD: Antegrade cardioplegia, retrograde cardioplegia or both? Ann Thorac Surg 1988;45:589-90. 3. Partington MT, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries. J THORAC CARDIOVASC SURG 1989;97:605-12. 4. Partington MT, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. II.
Advantages of antegradejretrograde cardioplegia to optimize distribution in jeopardized myocardium. J THORAC CARDIOVASC SURG 1989;97:613-22. 5. Fiore AC, N aunheim KS, Kaiser GC, et al. Coronary sinus versus aortic root perfusion with blood cardioplegia in elective myocardial revascularization. Ann Thorac Surg 1989; 47:684-8. 6. Guiraudon GM, Campbell CS, McLellan DG, et al. Retrograde coronary sinus versus aortic root perfusion with cold cardioplegia: randomized study of levels of cardiac enzymes in 40 patients. Circulation 1986;74(Pt 2):III I05-
IS. 7. Diehl JT, Eichhorn EJ, Konstam MA, et al. Efficacy of retrograde coronary sinus cardioplegia in patients undergoingmyocardial revascularisation: a prospective randomized trial. Ann Thorac Surg 1988;45:595-602. 8. Johnson RE, Dorsey LM, Moye SJ, Hatcher CR, Guyton RA. Cardioplegic infusion: the safe limits of pressure and temperature. J THORAC CARDIOVASC SURG 1982;83:81323. 9. Sarnoff SJ. Myocardial contractility as described by ventricular function curves: observations on Starling's law of the heart. Physiol Rev 1955;35:107-9. 10. Heineman FW, MacGregor DC, Wilson JG, Ninomiya J. Regional and transmural myocardial temperature distribution in cold chemical cardioplegia. J THORAC CARDIOVASC SURG 1981;81:851-9. II. Landymore RW, Tice D, Trehan N, Spencer F. Importance of topical hypothermia to ensure uniform myocardial cooling during coronary artery bypass. J THORAC CARDIOVASC SURG 1981;82:832-6. 12. Grondin CM, Helias J, Vouhe PR, Robert P. Influence of critical coronary artery stenosis on myocardial protection through cold potassium cardioplegia. J THORAC CARDIOVASC SURG 1981;82:608-15. 13. Hilton CJ, Teubl W, Acker M, etal. Inadequate cardioplegic protection with obstructed coronary arteries. Ann Thorae Surg 1979;28:323-34. 14. Vander Salm TJ, Okiki ON, Cutler BS, Paraskos JA, Ferulo J, Dagget W. Improved myocardial preservation by improved distribution of cardioplegic solutions. J THORAC CARDIOVASC SURG 1982;82:767-71. 15. Gundry SR, Sequiera A, Razzouk AM, McLaughlin JS, Bailey LL. Facile retrograde cardioplegia: transatrial cannulation of the coronary sinus. Ann Thorac Surg 1990; 50:882-7. 16. Noyez L, Knape JTA, Arnold BJ, et al. Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aortacoronary bypass grafting. Eur J Cardiothorac Surg 1992;6:377-81. 17. Flameng W, Van der Vusse PH, De Meyere R, et al. Intermittent aortic crossclamping versus St. Thomas' Hospital cardioplegia in extensive aorta-coronary bypass grafting. J THORAC CARDIOVASC SURG 1984;88:164-73. 18. Menasche P, Subayi JB, Veyssie L, Le DrefO, Chevret S, Piwnica A. Efficacy of coronary sinus cardioplegia in
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 5
patients with complete coronary artery occlusions. Ann Thorac Surg 1991;51:418-23. 19. Walter PJ, F1ameng W, Kindl R, Podzuweit T. Preservation of myocardial energy-rich phosphates by retrograde application of Bretschneider cardioplegia during aorta-coronary bypass surgery. Eur J Cardiothorac Surg 1988;2:2530. 20. Masuda M, Yonenga K, Shiki K, Morita S, Kohno H, Tokunaga K. Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs. J THORAC CARDIOVASC SURG 1986;92:255-63. 21. Shiki K, Masuda M, Yonega K, Asou T, Tokunaga K. Myocardial distribution of retrograde flow through the coronary sinus of the excised normal canine heart. Ann Thorac Surg 1986;41:265-71.
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22. Ludighausen MV. Nomenclature and distribution pattern of cardiac veins in man. In. Mohl W, Faxon D, Wolner W, eds. Clinics of CSL Darmstadt: Steinkopf Verlag, 1986: 13-32. 23. Gundry SR, Kirsh MM. A comparison of retrograde cardioplegia versus antegrade cardioplegia in the presence of coronary artery obstruction. Ann Thorac Surg 1984; 38:124-7. 24. Menasche P, Subayi JB, Piwnica A. Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. Ann Thorac Surg 1990;49:556-64. 25. Menasche P, Kucharski K, Mundler O. Adequate preservation of right ventricular function followingcoronary sinus cardioplegia: a clinical study. Circulation 1989;80(Pt 2): III 19-24.
Bound volumes available to subscribers Boundvolumesof THEJOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY are available to subscribers (only) for the 1993 issues {rom the Publisher, at a cost0[$75.00 [ordomestic, $98.25 [orCanadian, and $93.00[orinternational subscribers [or Vol.' 105(JanuaryJune) and Vol. 106 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertisingis removed.Copies are shipped within 60 days after publication of the last issueof the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, SubscriptionServices, 11830 Westline Industrial Drive, St. Louis, Missouri 63146-3318,USA; phone I (800) 453-4351 or (314) 453-4351. Subscriptions must be in force to qualify. Bound volumes are not availablein place of a regular JOURNAL subscription.
L. Noyez, MD,a Jacques A. M. van Son, MD, phD,a> T. van der Werf, MD,b J. T. A. Knape, MD,c J. Gimbrere, MD,d W. N. J. C. van Asten, PhD,a L. K. Lacquet, MD,a and W. Flameng, MD,e Nijmegen, The Netherlands, and Leuven, Belgium
From the Departments of Thoracic and Cardiac Surgery," Cardiology, b Anesthesiology," Intensive Care," University Hospital Nijmegen St. Radboud, Nijmegen, The Netherlands, and the Department of Cardiac Surgery" of the University Hospital of Leuven, Belgium. Address for reprints: L. Noyez, MD, Department of Thoracic and Cardiac Surgery, University Hospital Nijmegen St. Radboud, Postbus 9101,6500 HB Nijmegen, The Netherlands.
854
Received for publication July 23, 1991. Accepted for publication May 26, 1992. 'Current address: Division of Thoracic and Cardiovascular Surgery, Mayo Clinic, Rochester, Minn.
J
THORAC CARDIOVASC SURG
Copyright
@
1993;105:854-63
1993 by Mosby-Year Book, Inc.
0022-5223/93 $1.00 +.10
12/1/42475
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antegrade group, p = 0.0116). We conclude that retrograde cardioplegia provides better myocardial protection than antegrade cardioplegia in patients with three-vessel coronary artery disease and occlusion of the left anterior descending coronary artery who undergo myocardial revascularization with extensive use of the internal mammary artery. We also conclude that occlusion of the left anterior descending coronary artery is an essential parameter in the inhomogeneous distribution of antegrade cardioplegia. (J THORAC CARDIOVASC SURG 1993;105:854-63)
Adequate distribution of cardioplegic solution in the myocardium and adaptable strategies for its delivery in various clinical situations are two prerequisites for optimal myocardial protection, as described by Buckberg and Rosenkranz.' Currently there is an increasing interest in retrograde cardioplegia in aorta-coronary bypass surgical intervention because of inhomogeneous distribution of cardioplegic solution during antegrade cardioplegia delivery as a result of coronary artery stenosis and use of the internal mammary artery as graft of choice, which prohibits antegrade delivery of cardioplegic solution.' In experimental studies there is evidence of superior myocardial protection of the left ventricle with the use of retrograde cardioplegia, even with patent coronary arteries, but there is less favorable protection of the right ventricle.3• 4 Clinical studies concerning retrograde cardioplegia, however, are few and inconclusive."? This report is a prospective, randomized, clinical trial studying the effect on myocardial performance of antegrade and retrograde cardioplegia in patients with three-vessel coronary artery disease, who underwent aorta-coronary bypass surgical intervention with extensive use of the internal mammary artery. Because the most extreme situation of coronary artery disease is an occlusion, which prohibits antegrade delivery of cardioplegic solution, special attention was given to patients with an occluded left anterior descending coronary artery (LAD).
Patients and methods Patient population. We studied 60 patients who underwent aorta-coronary bypass surgical intervention. All patients had three-vessel coronary artery disease. Exclusion criteria for the study included the following: reoperations, combined procedures, poor left ventricular function (with ejection fraction <0.30) and emergency aorta-coronary bypass grafting (with evolving myocardial infarction, ischemia that is unresponsive to medical therapy, and cardiogenic shock). The patients were randomly separated into two groups: group A tn = 30) received antegrade cardioplegia, and group B (n = 30) received retrograde cardioplegia.Ethical approval and informed consent were obtained. TableI shows the preoperative data. Obesity was defined as more than 100/0 excess body weight; diabetes, as positive results onglucose tolerance test, use of oral antidiabetic medication, or insulin dependency; hypertension, as a systolic blood pressure of
more than 160 mm Hg or a diastolic pressure of more than 100 mm Hg; hyperlipidemia, as a cholesterol level of more than 6.4 mrnol/L or a triglyceride level of more than 2 mmol/L, All previous medication, such as nitrates, Ca++ -entry blockers, and beta-blockers. was continued until midnight before the operation. Surgical technique. A standardized anesthetic technique was used, with intravenous doses of fentanyl citrate (60 Ilg/kg) for anesthesia, pancuronium (0.1 mg /kg) for muscle relaxation, and midazolam (0.07 to 0.1 mg/kg per minute) for amnesia. A Swan-Ganz catheter (Baxter Healthcare Corp., Edwards Division, Irvine, Calif.) was introduced into the pulmonary artery via the internal jugular vein. All operations were performed by one surgeon (L N.) to avoid the variability that would have arisen with multiple surgeons. The distal anastomoses were performed during a single period of crossclamping, and proximal anastomoses were performed with a partial occluding clamp. Standard bypass techniques were used with a Cobe C.M.L-Excel and Maxima membrane oxygenator and a roller pump (Cobe BCT, Inc., Lakewood, Colo.) while the patient underwent systemic hypothermia (with a rectal temperature of 28° C), and moderate hemodilution. Myocardial protection was achieved by infusion of cold (4° C) St. Thomas' Hospital cardioplegic solution (300 ml/rn"), until asystole occurred; protection was maintained by reinfusion of I00 ml of solution per square meter every 25 to 30 minutes, or as often as needed. In group A, the cardioplegic solution was infused in the aortic root with a pressure of ± 100 mm Hg,8 and, in group B, we performed retrograde delivery of cardioplegic solution. In both groups, an additional dose of 25 ml of cardioplegic solution was infused through the venous grafts that were constructed first. The coronary sinus was cannulated transatrially, as described by Gundry and associates.P We used a Gundry RSCP cannula with obturator (DLP, Inc., Grand Rapids, Mich.) or a Buckberg cannula (Research Medical, Inc., Salt Lake City, Utah). Coronary sinus pressure never exceeded 50 mm Hg. In all patients, a left ventricular vent was placed through the right superior pulmonary vein. Patienttemperature was kept between 26° and 28° C, and slushed ice was used as topical cooling. Myocardial septal temperatures were recorded at the moment of asystole and after infusion of the total dose of cardioplegic solution. Before the patient was weaned from extracorporeal circulation, rewarming was done until rectal temperature reached 35° C, and the hematocrit value was increased to a minimum of 24%. Intravenous fluid therapy was intended to achieve optimal filling pressures for the actual myocardial performance, which was monitored by frequent determinations of cardiac filling pressures and calculations of stroke work index and cardiac index. The aorta was decannulated after 5 minutes of hemodynamic stability after cessation of cardiopulmonary bypass.
856
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Table II. Intraoperative patient data
Table I. Preoperative patient data
No. Male/female Age (yr) BSA (m'') NYHA Obesity Hypertension Diabetes Hyperlipidemia LAD occlusion
Group A
Group B
30 23/7 57.3 ± 8.1 (34-69) 1.94 ± 0.15 (1.6-2.1) 3.1 ± 0.59 (2-4) 8 13 5 10 9
30 25/5 56.1 ± 8.1 (37-69) 1.88 ± 0.10 (1.6-2.4) 3.1 ± 0.5 (2-4) 6 14 3 12 10
p Value NS NS NS NS NS NS NS NS NS
Group data are expressed as mean ± standard deviation. NS, Not significant; BSA, body surface area; NYHA, New York Heart Association classification. Indexes for evaluation of myocardial protection. We assessed recovery of cardiac function in all patients by monitoring systolic (SAP), diastolic (DAP), mean arterial (MAP) blood pressure, mean right atrial pressure (RAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and heart rate (HR). Cardiac output (Q) was measured with the thermodilution technique. Derived hemodynamic indexes were calculated as follows: Cardiac index (QO = Q/Bodysurfacearea (Lyrninper square meter); Stroke index (SO = QI/HR (nil/min per square meter); Left ventricular stroke work index (L VSWI) = SI(MAP PCWP) . 0.0136 (gm/rnin per square meter); Right ventricular stroke work index (RVSWI) = SI(PAP - RAP) . 0.0136 (gm/rnin per square meter); Systemic vascular resistance index (SVRI) = (MAP - RAP)/Q . 80 (dyne. sec . cm"). These hemodynamic variables were measured (I) after induction of anesthesia, (2) after cessation of cardiopulmonary bypass, after a duration of 5 minutes of hemodynamic stability, just before administration of protamine hydrochloride (this registration is further noted as "5 minutes after cessation of cardiopulmonary bypass"), and (3) 6 hours after the operation, in the intensive care unit. At I, 3,6, 12, and 24 hours after the operation, venous blood samples were taken for determination of creatine kinase isoenzyme (CK-MB). Clinical outcome. Intraoperative myocardial infarction was defined as the development of a new Q wave or a concentration of CK-MB of at least 10% or both. Low cardiac output was defined as the need for inotropic support in which dopamine requirements increased 4 ,ug/kg per minute for at least 12 hours or a cardiac index less than 2.2 L/min per square meter. Preoperative and postoperative electrocardiograms were compared, and special attention was given to the appearance of atrioventricular conduction disturbances. There was special attention for problems caused by cannulation and decannulation of the coronary sinus. Statistical analysis. Quantitative data were analyzed with a paired Student t test or a Wilcoxon test when appropriate, and a multivariate analysis was performed. A p value of less than 0.05 indicated that the difference was unlikely to be due to chance alone. Data were expressed as mean values ± standard deviation.
Group A
GroupB
No. 30 30 Cardioplegic solution (ml) 913.3 ± 131.6 1108 ± 204.6 Asystole time (sec) 57.5 ± 27.5 74.2 ± 26.9 (28-148) (32-121 ) Asystole temp (0 C) 20.8 ± 2.3 18.3 ± 2.3 (17-24) (18-22) Myocard temp (0 C) 16.4±3.1 14.9 ± 2.8 (12-19) (12-18) Bypass time (min) 120.1 ± 28.4 127.8 ± 25.7 (78-165) (65-165) Crossclamp time (min) 80.2 ± 13.8 79.1 ± 10.6 (48-98) (63-98) No. of grafts 3.1 ± 0.3 3.2 ± 0.4 (3-4) (3-5) Distal anastomoses (No.) 5.2 ± 1.1 4.6 ± I (4-7) (4-7) Dista1lMA-anast (No.) 3.5 ± 0.5 3.3 ± 0.6 (3-4) (2-5)
p Value p = 0.Q2
NS NS NS NS NS NS NS NS
Group data are expressed as mean ± standard deviation. NS. Notsignificant; Asystole time, time to reach asystole; Asystole temp. septal temperature at the moment ofasystole; Myocard temp, septal temperature after infusion ofthe initial dose ofcardioplegic solution; Distal I MA-anast, distal anastomoses performed with theinternal mammary artery.
Results The intraoperative data are shown in Table II. The mean time to reach asystole in group B was longer than in group A, but the difference did not reach statistical significance. Septal temperature at the moment of asystole and after infusion of the initial dose of cardioplegic solution were not significantly different between the two groups. The total doses of cardioplegic solution were significantly higher in group B; however, the postbypass hematocrit values were comparable for both groups (group A, 26% ± I %; group B, 26% ± 2%). In all patients at least one internal mammary artery was used as graft, either single or sequential, with bilateral use of the internal mammary artery in 80% of the patients. Of the distal anastomoses, 75% were done with the internal mammary artery. The recovery of hemodynamics is summarized in Table III. There was no significant difference in the prebypass values between groups A and B. Comparing the prebypass values with those obtained 5 minutes after cessation of cardiopulmonary bypass, we observed an increase of heart rate, pulmonary artery pressure, pulmonary capillary wedge pressure and a decrease of mean arterial pressure, L VSWI, and R VSWI, which were not statistically significant. Right atrial pressure increased significantly (p < 0.001) in the patients who underwent antegrade cardioplegia and decreased, not significantly, in patients who underwent retrograde cardioplegia. In the two
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Table III. Hemodynamic patient data A No. HR (beats/min) MAP(mm Hg) RAP (mm Hg) PAP(mm Hg) PCWP (mm Hg) Q (Lzrnin) QI (Lyrnin per square meter) SI (rnl/rnin per square meter) LVSWI (gm/rnin per square meter) RVSWI (gm/rnin per square meter) SVRI (dyne. sec· cm- s)
30
61.5 ± 79.4 ± 7.6 ± 17.6 ± 9.9 ± 4.8 ± 2.5 ± 40.4 ± 36.9 ± 6.0 ± 1985 ±
AI
B
BI
A2
B2
83.2 ± 9.1 86.0 ± 8.9 8.2 ± 2.3 17.l±4.1 10.2 ± 4.4 5.3 ± 1.3 2.7 ± 0.3 32.2 ± 4.7 35.5±10.1 4.6 ± 1.8 1830 ± 690
84.1 ± ILl 88.3 ± 9.2 7.1 ± 1.7 17.3 ± 4.2 8.8 ± 2.0 5.3 ± 1.1 2.6 ± 0.8 33.1 ± 9.3 34.7 ± 9.2 4.8 ± 1.4 1880±735
30
7.1 10.2 1.8 4.4 3.1 1.3
0.9 9.4 8.9 1.1 820
58.9 ± 77.2 ± 7.9 ± 15.8 ± 9.5 ± 4.7 ± 2.5 ± 41.9 ± 38.12 ± 5.6 ± 2080 ±
8.0 8.4 1.2 3.6 3.0 1.1
1.2 6.2 7.7 1.0 790
81.5 ± 69.9 ± 9.3 ± 18.1 ± 11.0 ± 5.8 ± 2.6 ± 39.7 ± 30.5 ± 5.1 ± 1245 ±
10.2 9.0 1.8* 2.2 2.4 1.6 0.6 9.5 7.3 0.6 540*
80.2 ± 73.3 ± 6.4 ± 16.1 ± 9.7 ± 5.5 ± 2.8 ± 37.0 ± 31.7 ± 4.9 ± 1380 ±
11.4 7.2 1.1 3.4 3.3 1.8 0.8 6.5 4.6 0.8 430*
Data are expressed as mean values ± standard deviation A. Data group A after anesthesia-induction; B, data group B after anesthesia-induction; A' and B', data group A and B 5 minutes after cessation of cardiopulmonary bypass; A 1 and B2 , data group A and B 6 hours after operation; HR, heart rate; MAP, mean arterial blood pressure; RAP, mean right atrial pressure; PAP. mean pulmonary artery pressure; pewp, pulmonary capillary wedge pressure; Q, cardiac output; Ql, cardiac index; Sf, stroke index; SVRf, systemic vascular resistance index. *p < 0.05 versus preoperative value.
groups, systemic vascular resistance was significantly decreased after bypass but returned to normal values after 6 hours. For the values that were recorded 6 hours after the operation, there was no statistically significant difference in comparison with the prebypass values. We found that patients with an occlusion of the LAD who underwent antegrade cardioplegia had a higher septaltemperature at the moment of asystole and after infusion of the initial dose of cardioplegia than did other patients. Therefore, myocardial protection in the former may have been worse. To quantify this experience, we compared the difference in the LVSWI before cardiopulmonary bypass and 5 minutes after cessation of cardiopulmonary bypass with the higher septal temperature achieved after infusion of the initial dose of cardioplegic solution (Fig. 1and Fig. 2). The statistical representations of8ofthe 10patients with an occluded LAD who received retrograde cardioplegia are situated in the left lower corner of Fig. 1; the representations of patients with an occlusion of the LAD who received antegrade cardioplegia areessentiallysituated in the right upper corner of Fig. 2.The importance of the LAD occlusion was evaluated bymultivariateanalysis. We found a statistically significant difference in the hemodynamic recovery of the left ventricle 5 minutes after cessation of cardiopulmonary bypass (p = 0.012), depending on the status ofthe LAD. Therefore, weseparated and analyzed the data of patients with an occlusion of the LAD in the antegrade group (n = 9) and in the retrograde group (n = 10). We see that the septal temperature at the moment of asystole (22.6 ± 2.1 0 C versus 19.3 ± 1.1 0 C, P = 0.008) and after infusion of the initial dose of cardioplegic solution (17.2 ± 2.1 C versus 13.5 ± 2.1 C, P = 0.005) was 0
0
significantly higher in the antegrade group. The recovery of the hemodynamics of all patients with an occluded LAD is summarized in Table IV. Before bypass there was no significant difference between mean arterial, pulmonary arterial, or pulmonary capillary wedge pressures of the two groups, but there were significant differences for these values in the immediate postoperative period. In the immediate postoperative period, the patients with an occluded LAD who underwent antegrade cardioplegia showed a significant increase of the mean right atrial pressure, as was the case for the entire antegrade group, whereas the mean arterial pressure decreased significantly (p = 0.0003). In the two groups heart rate increased, but not significantly. In the two groups the systemic vascular resistance was significantly decreased after bypass. In both groups the cardiac index 5 minutes after cessation of bypass was higher than before bypass, but the increase did not reach statistical significance. The LVSWI was significantly different between the two groups (p = 0.04) in the postoperative period, with a decrease in the antegrade and retrograde groups to 71% and 85% of control value, respectively (p = 0.0116). Neither group had a significant change in the RVSWI before and after the operation. In Figs. 3 and 4, filling pressure and stroke work are represented in a classic diagram as proposed by Sarnoff." There was a decrease of LVSWI, with an increase of the wedge pressure, in only 2 of 10 patients who underwent retrograde cardioplegia (Fig. 3). In contrast, 7 of9 patients who underwent antegrade cardioplegia experienced the same course (Fig. 4). Analysis of the data of the patients without occlusion of the LAD did not show a significantly different preservation of the LVSWI between antegrade and retrograde
The Journal of Thoracic and Cardiovascular Surgery May 1993
8 5 8 Noyez et al.
A LVSWI
20
~
15 0
-
10
•i •
0 0
~
-
12
13
14
0
5
• D
o
10
11
•
0 0
-
0
15 °C
o
LAD-occlusion
Q
0 0
16
• 17
18
19
20
No LAD-occlusion
Fig. 1. Plot comparing the differencein LVSWI before bypass and LVSWI 5 minutes after cessation of cardiopulmonary bypass (ilLVSWI) with the septal temperature (0C) reached after infusion of the initial dose of cardio-
plegic solution for each patient who underwent retrograde cardioplegia.
t::..LVSWI
20
• •• • •
0 15
0 10
• • § ~
0
8
6
~
0
o
10
0
0
0
'-'
~
-
8
0 0
17
18
0
4
11
12
•
13
14
LAD-occclusion
15 °C
16
o
19
20
No LAD-occclusion
Fig. 2. Plot comparing the difference in LVSWI before bypass and LVSWI 5 minutes after cessation of cardiopulmonary bypass (fiLVSWI) with the septal temperature (0C) reached after infusion of the initial dose of cardio-
plegic solution for each patient who underwent antegrade cardioplegia.
cardioplegia. The release of the cardiac-specific enzyme CK-MB in group A and group B was not different, nor was it different in the two groups with an occlusion ofthe LAD (Fig. 5). In all patients, the clinical outcome was excellent. There were no deaths and no perioperative infarction. Three patients, two in the retrograde and one
in the antegrade group, showed signs of low cardiac output. These were the same patients who needed positive inotropic support after weaning from bypass. Both before and after the operation, all patients had a regular sinus rhythm. No rhythm disturbances or technical problems related to the delivery of cardioplegic solution were noted.
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LVSWI (gm.m/m 2) 60,--------------------------------, 50 40 30
20 10
O'-------'-------'-------L.----------.J
o
5
*
10
PCWP (rnm Hg)
before bypass
20
15
+ 5 min. after bypass
Fig. 3. Plot representing relationship between LVSWI and pulmonary capillary wedge pressure (peWp) before bypass and 5 minutes after bypassfor each patient who underwent retrograde cardioplegia.
Table IV. Hemodynamic data ofpatients with an occluded LAD Prebypass ACP
RCP
ACP
RCP
9 ± ± ± ± ± ± ± ± ± ± ±
10 57.6 ± 8.7 76.6 ± 6.5 7.6 ± 1.3 15.4 ± 4.4 9.1 ± 3.5 4.7 ± 0.8 2.4 ± 0.6 42.8 ± 7.7 38.9 ± 6.5 5.9 ± 2.6 2135 ± 790
9 ± ± ± ± ±
10 77.0 ± 11.8 75.8 ± 6.7*t 5.5 ± 2.4* 15.3 ± 4.4* 9.6±3.1* 5.4 ± 1.1 2.8 ± 0.6 37.2 ± 6.6 33.3 ± 4.5*t 5.0 ± 1.9 1420 ± 460§
No. HR (beats/min) MAP(mm Hg) RAP (rnm Hg) PAP (mm Hg) PCWP (mm Hg) Q (Lyrnin) QI (Lyrnin per square meter) SI (rnl/rnin per square meter) LVSWI (gm/rnin per square meter) RVSWI (grri/rnin per square meter) SVRI (dyne· sec· cm- s)
5 min after cessation of CPS
60.6 81.6 7.7 18.2 10.7 4.8 2.4 41.1 38.8 6.1 1978
7.6 10.3 2.7 4.9 3.7 1.0 0.6 10.8 10.5 1.8 800
81.4 11.7 II.I§ 65.2 10.7 2.2§ 20.7 2.7 14.0 2.6 6.2 ± 1.3 3.1 ± 0.8 39.9 ± 12.1 27.3 ± 7.6 5.1 ± 1.5 1255±510§
Data are expressed as mean values ± standard deviation. ACP, Antegrade cardioplegia; RCP, retrograde cardioplegia; CPB, cardiopulmonary bypass; H R, heart rate; MAP, mean arterial blood pressure; RAP, mean right atrial pressure; PAP, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; Q. cardiac output; QI, cardiac index; SI, stroke index; SVRI, systemic vascular resistance index. 'p < 0.05 ACP (5 minutes after cessation of cardiopulmonary bypass) versus RCP (5 minutes after cessation of cardiopulmonary bypass). tp < 0.05 difference between ACP (prebypass) and RCP (prebypass) versus difference between ACP (5 minutes after cessation of cardiopulmonary bypass) and RCP (5 minutes after cessation of cardiopulmonary bypass). §p < 0.05 versus prebypass value.
Discussion Critical coronary artery stenoses and occlusions may resultin inhomogeneous distribution of antegradely delivered cardioplegic solution and, consequently, poor local myocardial protection.!" 11 Experimental and clinical studies have shown an increase in myocardial energy needs in these jeopardized areas and a depression of the left ventricular function after reperfusion.U'!" Direct
antegrade graft perfusion can circumvent this limitation of antegrade cardioplegia, but with the increasing use of the internal mammary artery for grafting, this becomes technically imposslble.? In these situations, retrograde administration of cardioplegic solution via the coronary venous system is a valuable alternative strategy. The experimental work of Partington and associates-" and the development of techniques 15 for blind cannulation of
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8 6 0 Noyez et at.
LVSWI (gm.m/m 2)
60,-----------------------------,
50 40 30 20 10 0'------------'----------'-----------'------------' o 5 15 20 10
PCWP (rnrn Hg)
*
before bypass
+ 5 min. after bypass
Fig. 4. Plot representing relationship between LVSWI and pulmonarycapillary wedge pressure (PCWP) before bypass and 5 minutes after bypass for each patient who underwent antegrade cardioplegia.
Fig. 5. Release of CK-MB isoenzyme in the first 24 hours after the operation in patients with an occlusion of the LAD. The data represent mean values ± standard deviation. the coronary sinus have contributed to the renewal of interest in the use of retrograde cardioplegia in myocardial revascularization. In our study, we were unable to show better preservation of left ventricular myocardial function with retrograde cardioplegia for the group as a whole. When there was an occlusion of the LAD, however, the preservation of left ventricular function was significantly better when retrograde cardioplegia was used. With an occlusion of
the LAD, the LVSWI decreased to 85% of the initial value when the patients received retrograde cardioplegia versus 71% of the initial value that was achieved when antegrade cardioplegia was used. In the majority of patients with antegrade cardioplegia a decrease of LVSWI was accompanied by an increase in pulmonary capillary wedge pressure, whereas in most patients with retrograde cardioplegia, the decrease in LVSWI, which was less than that of the antegrade group, was accompa-
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 5
nied by a decrease in pulmonary capillary wedge pressure. This observation suggests a better preservation of left ventricular contractility in patients with retrograde cardioplegia. This conclusion, however, is valid only if pulmonary capillary wedge pressure reflects left ventricular diastolic volume. An increase in pulmonary capillary wedge pressure may also be elicited by impaired relaxation or increased stiffness of the left ventricular myocardium, which effects may be inherent to the technique of antegrade cardioplegia per se. Volume-derived indexes should be studied in the future, for instance, with esophageal echocardiography in the operating room. The observed decrease of the L VSWI is comparable to the decrease in left ventricular myocardial performance that we noticed in our previous clinical trial!" and other studies." 17, 18 The superior preservation of left ventricular function in patients with an LAD occlusion in the retrograde group, as observed in this study, is caused to a certain extent by patient selection and extensive use of the internal mammary artery for bypass grafting. The patient group with total occlusion of the LAD approximates the experimental model of Partington and associates-" in which the LAD was ligated. Previous clinical trials"? were inconclusive concerning the superior myocardial protection achieved with retrograde cardioplegia in patients with coronary artery disease, but in none of these studies was there as extensive coronary artery disease as in our study; also, the internal mammary artery was not used extensively for bypass grafting. Fiore and associates described a mean of 2.9 diseased vessels in their study, and we presume therefore that patients with fewer than three diseased vessels were included. In addition, only 65% of the patients received internal mammary arteries as graft. Guiraudon and associates" do not mention the severity of coronaryartery disease or whether revascularization was donewith the internal mammary artery. The importance of the severity and extent of the coronary artery disease isclearly shown in our study, in which multivariate analysis showed that occlusion of the LAD is an essential variablein the distribution of cardioplegic solution. In our study, it was impossible, with a limited number of patients, to analyze at what degree of coronary artery disease retrograde delivery of cardioplegic solution becomes superior to antegrade. In the study by Diehl and associates,' all patients had isolated three-vessel coronary arterydisease, and the internal mammary artery was used in 80% of the patients. The latter study was flawed, however, because of the fact that each patient received an initialdose of cardioplegic solution through the aortic root. Inour study, cardioplegic solution was delivered through
Noyez et al.
86 I
the vein grafts, and topical slushed ice was used in all patients; although these techniques may have reduced the difference in left ventricular preservation between the antegrade and retrograde groups, they are part of our goal to achieve optimal myocardial protection. Myocardial biopsy samples were not taken in this study, but it has been shown that in patients with threevessel disease and a significant stenosis in the LAD, the preservation of energy-rich phosphates during ischemic cardiac arrest is better with retrograde than with antegrade cardioplegia. 19 It is known that a decrease in energy-rich phosphates is a trigger for the sequence of events that leads to cell death. Better preservation of energy-rich phosphates results in improved tolerance of ischemia and can prevent postischemic myocardial dysfunction, as suggested in a recent experimental study.i" The R VSWI was not statistically different before and after bypass in both groups, which is in contrast with the results of the experimental study of Partington and associates.': 4 in which the RVSWI in dogs was decreased. We hypothesize that the less favorable protection of the right ventricle in dogs, in comparison with humans, may be related to the anatomic difference in venous drainage of the right and left ventricles between both. Anatomic studies in dogs?' have shown that most of the right ventricle and the posterior part of the interventricular septum are not drained by the coronary sinus. In contrast, the cardiac venous drainage in human beings seems to be more balanced.F The equal distribution of the venous system over the human heart is confirmed by excellent cooling of the entire heart by retrograde cold cardioplegia as reported in this and other studies- 6, 23, 24 and by application of radionucIide techniques." Delay in cardiac arrest is described as a major disadvantage of retrograde cardioplegia' In our study, we did not observe a significant difference between the two groups in the time that was needed to reach asystole. This is in contrast with Fiore and associates who reported times of 30 and 75 seconds in the antegrade and retrograde groups, respectively, to achieve electromechanical arrest. Our time to achieve asystole in the retrograde group is comparable; in the antegrade group, our time is much longer, which is certainly related to the more extensive coronary artery disease in our patients. The total doses of cardioplegic solution are significantly higher in patients who underwent retrograde cardioplegia, which is not only related to the capacity of the coronary venous system but also to the facility of delivery of retrograde cardioplegic solution without need for interruption of the operation. The latter quality of retrograde cardioplegia is especially advantageous during the performance
The Journal of Thoracic and Cardiovascular Surgery May 1993
8 6 2 Noyez et al.
of sequential anastomoses with the internal mammary artery and during testing for leakage of a side-to-side anastomosis, because the grafted myocardial area remains free from fibrillation. Blind cannulation of the coronary sinus circumvents bicaval cannulation, caval snares, and an atriotomy for visualization of the coronary sinus. There were no problems during cannulation and decannulation of the coronary sinus in our study, but our extensive experience with this technique in previous patients has certainly contributed to the lack of complications. The good clinical outcome in both groups in this study is certainly also related to our patient selection and surgical strategy. We operated on a mainly young population to allow for extensive (bilateral) use of the internal mammary artery as a graft, and we did not consider it ethical to include patients with an ejection fraction of less than 0.30. Patients with evolving myocardial infarction, with myocardial ischemia not responsive to medical therapy, and with cardiogenic shock were excluded because successful myocardial protection and revascularization of an acutely ischemic myocardial region is related to several factors and not only to the anatomic occlusion of a coronary artery. Although the clinical outcome was excellent in both groups of patients, early recovery of left ventricular function was better in patients with an occluded LAD who underwent retrograde cardioplegia. This observation correlates with the experimental results that were obtained by the groups headed by Partington and Buckberg. 3, 4 We conclude that retrograde cardioplegia is superior to antegrade cardioplegia with regard to myocardial protection in patients with three-vessel coronary artery disease including occlusion of the LAD who are subjected to myocardial revascularization with extensive use of the internal mammary artery. In addition, we conclude that occlusion of the LAD is a contraindication for the use of antegrade cardioplegia. REFERENCES I. Buckberg GD. Rosenkranz EL. Principles of cardioplegic myocardial protection. In: Roberts AJ, ed. Myocardial protection in cardiac surgery. New York: Dekker, 1986:7194. 2. Buckberg GD: Antegrade cardioplegia, retrograde cardioplegia or both? Ann Thorac Surg 1988;45:589-90. 3. Partington MT, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries. J THORAC CARDIOVASC SURG 1989;97:605-12. 4. Partington MT, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. II.
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IS. 7. Diehl JT, Eichhorn EJ, Konstam MA, et al. Efficacy of retrograde coronary sinus cardioplegia in patients undergoingmyocardial revascularisation: a prospective randomized trial. Ann Thorac Surg 1988;45:595-602. 8. Johnson RE, Dorsey LM, Moye SJ, Hatcher CR, Guyton RA. Cardioplegic infusion: the safe limits of pressure and temperature. J THORAC CARDIOVASC SURG 1982;83:81323. 9. Sarnoff SJ. Myocardial contractility as described by ventricular function curves: observations on Starling's law of the heart. Physiol Rev 1955;35:107-9. 10. Heineman FW, MacGregor DC, Wilson JG, Ninomiya J. Regional and transmural myocardial temperature distribution in cold chemical cardioplegia. J THORAC CARDIOVASC SURG 1981;81:851-9. II. Landymore RW, Tice D, Trehan N, Spencer F. Importance of topical hypothermia to ensure uniform myocardial cooling during coronary artery bypass. J THORAC CARDIOVASC SURG 1981;82:832-6. 12. Grondin CM, Helias J, Vouhe PR, Robert P. Influence of critical coronary artery stenosis on myocardial protection through cold potassium cardioplegia. J THORAC CARDIOVASC SURG 1981;82:608-15. 13. Hilton CJ, Teubl W, Acker M, etal. Inadequate cardioplegic protection with obstructed coronary arteries. Ann Thorae Surg 1979;28:323-34. 14. Vander Salm TJ, Okiki ON, Cutler BS, Paraskos JA, Ferulo J, Dagget W. Improved myocardial preservation by improved distribution of cardioplegic solutions. J THORAC CARDIOVASC SURG 1982;82:767-71. 15. Gundry SR, Sequiera A, Razzouk AM, McLaughlin JS, Bailey LL. Facile retrograde cardioplegia: transatrial cannulation of the coronary sinus. Ann Thorac Surg 1990; 50:882-7. 16. Noyez L, Knape JTA, Arnold BJ, et al. Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aortacoronary bypass grafting. Eur J Cardiothorac Surg 1992;6:377-81. 17. Flameng W, Van der Vusse PH, De Meyere R, et al. Intermittent aortic crossclamping versus St. Thomas' Hospital cardioplegia in extensive aorta-coronary bypass grafting. J THORAC CARDIOVASC SURG 1984;88:164-73. 18. Menasche P, Subayi JB, Veyssie L, Le DrefO, Chevret S, Piwnica A. Efficacy of coronary sinus cardioplegia in
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patients with complete coronary artery occlusions. Ann Thorac Surg 1991;51:418-23. 19. Walter PJ, F1ameng W, Kindl R, Podzuweit T. Preservation of myocardial energy-rich phosphates by retrograde application of Bretschneider cardioplegia during aorta-coronary bypass surgery. Eur J Cardiothorac Surg 1988;2:2530. 20. Masuda M, Yonenga K, Shiki K, Morita S, Kohno H, Tokunaga K. Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs. J THORAC CARDIOVASC SURG 1986;92:255-63. 21. Shiki K, Masuda M, Yonega K, Asou T, Tokunaga K. Myocardial distribution of retrograde flow through the coronary sinus of the excised normal canine heart. Ann Thorac Surg 1986;41:265-71.
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22. Ludighausen MV. Nomenclature and distribution pattern of cardiac veins in man. In. Mohl W, Faxon D, Wolner W, eds. Clinics of CSL Darmstadt: Steinkopf Verlag, 1986: 13-32. 23. Gundry SR, Kirsh MM. A comparison of retrograde cardioplegia versus antegrade cardioplegia in the presence of coronary artery obstruction. Ann Thorac Surg 1984; 38:124-7. 24. Menasche P, Subayi JB, Piwnica A. Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. Ann Thorac Surg 1990;49:556-64. 25. Menasche P, Kucharski K, Mundler O. Adequate preservation of right ventricular function followingcoronary sinus cardioplegia: a clinical study. Circulation 1989;80(Pt 2): III 19-24.
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