Efficacy of Retrograde Coronary Sinus Cardioplegia in Patients Undergoing Myocardial Revascularization: A Prospective Randomized Trial

ORIGINAL ARTICLES

Efficacy of Retrograde Coronary Sinus Cardioplegia in Patients Undergoing Myocardial Revascularization: A Prospective Randomized Trial James T. Diehl, M.D., Eric J. Eichhorn, M.D., Marvin A. Konstam, M.D., Douglas D. Payne, M.D., Arthur R. Dresdale, M.D., Robert M. Bojar, M.D., Hassan Rastegar, M.D., Joseph J. Stetz, M.D., Deeb N. Salem, M.D., Raymond J. Connolly, Ph.D, and Richard J. Cleveland, M.D. ABSTRACT The efficacy of retrograde coronary sinus cardioplegia (RCSC) administered through the right atrium compared with aortic root cardioplegia (ARC) has not been examined critically in patients undergoing coronary artery bypass grafting (CABG). Twenty patients having elective CABG were randomized prospectively to receive cold blood ARC (Group I, 10 patients) or cold blood RCSC (Group 11, 10 patients). Patient demographics were similar in both groups. Ventricular function was assessed preoperatively by radionuclide ventriculography and postoperatively by simultaneous hemodynamic and radionuclide ventriculographic studies with volume loading. There was no change in ejection fraction (EF) (preoperative versus postoperative value) in Group I (50 f 6% versus 53 f 6%)but in group 11, at similar peak systolic pressure and similar left ventricular end-diastolic volume index (LVEDVI), LVEF improved significantly (49 f 6% versus 60 f 12%, p < 0.05). Postoperative ventricular function (stroke work index versus EDVI) for the left ventricle and right ventricle were similar in both groups. Evaluation of postoperative LV systolic function (end-systolic blood pressure versus end-systolic volume index) and diastolic function (pulmonary capillary wedge pressure versus EDVI) were also similar in both groups. Retrograde coronary sinus cardioplegia is as effective as ARC for intraoperative myocardial protection, and provides excellent postoperative function in patients undergoing elective CABG.

The concept of retrograde perfusion of the coronary venous system during open-heart operations remained dormant until the late 1970s when interest in the coronary sinus as a route for delivery of cardioplegia reemerged. Retrograde coronary sinus cardioplegia (RCSC) has been employed extensively for aortic valve operations at several European centers [5, 61. The importance of uniform myocardial distribution of cardioplegia beyond the coronary stenosis, which is attainable with RCSC, has been well demonstrated experimentally [7-141. However, RCSC has not been extensively utilized for patients undergoing coronary artery bypass grafting (CABG). The technique of direct cannulation of the coronary sinus has resulted in atrioventricular block and rupture of the sinus [15]. How effectively the right ventricle is perfused from the coronary sinus is another concern with this technique [16]. An innovative method of delivering RCSC through the right atrium was recently proposed by Fabiani and associates [17]. This method obviates direct cannulation of the coronary sinus and overcomes many of the theoretical concerns regarding right ventricular (RV) preservation. However, distention of the right ventricle in the arrested heart, inherent with this technique, raised other questions about postoperative RV function. The present study was undertaken in patients undergoing CABG to prospectively evaluate the efficacy of right atrial RCSC compared with standard aortic root cardioplegia (ARC) in preserving postoperative ventricular function.

Material and Methods Retrograde coronary sinus perfusion was introduced in 1956 to facilitate operations on the aortic valve [l-31. A decade later, this technique was suggested as a means of intraoperative myocardial protection during coronary artery procedures 141. Although theoretically attractive for both of these applications, retrograde coronary sinus perfusion was eclipsed clinically by techniques that directly perfuse the coronary arteries. From the Departments of Cardiothoracic Surgery and Cardiology, New England Medical Center Hospital and Tufts University School of Medicine, Boston, MA. Presented at the Twenty-third Annual Meeting of The Society of Thoracic Surgeons, Toronto, Ont, Canada, Sept 21-23, 1987. Address reprint requests to Dr. Diehl, New England Medical Center Hospital, 750 Washington St, Box 266, Boston, MA 02111.

Twenty patients undergoing CABG during an eightmonth period were recruited for this study. All patients had isolated three-vessel coronary artery disease with preserved left ventricular (LV) function (ejection fraction [EF] greater than 40%) at cardiac catheterization. There was no clinical or ventriculographic evidence of mitral regurgitation and no clinical evidence of tricuspid regurgitation in any patient. The same surgeons performed all operations (J. T. D. and D. D. P.). The experimental protocol was fully explained to all patients, and a consent form was obtained for randomization of cardioplegia and performance of postoperative studies. This method of obtaining consent was approved by the institutional human investigation committee at New England Medical Center Hospitals. Patients were ran-

595 Ann Thorac Surg 45:595-602, June 1988. Copyright 0 1988 by The Society of Thoracic Surgeons

596 The Annals of Thoracic Surgery Vol 45 No 6 June 1988

domized on the day of operation to receive either ARC (Group I) or right atrial RCSC (Group 11). All patients had preoperative gated radionuclide ventriculography.

Operative Techniques Induction and maintenance of anesthesia was achieved with fentanyl (75 pg per kilogram of body weight), pancuronium bromide (100 pg/kg), lorazepam, and enflurane. Patients were ventilated with 100% oxygen. Ascending aortic and bicaval cannulas were used to establish cardiopulmonary bypass. The cavae were snared around the venous cannulas in all patients. Moderate systemic hypothermia (30°C) and hemodilution (20 to 25% hematocrit) were maintained during cardiopulmonary bypass. The aortic root was routinely vented during the cross-clamp period. Topical hypothermia and multidose cold blood cardioplegia (dilution of 4:1, blood to cardioplegia) were utilized in all patients. In Group I patients, cardioplegia was administered exclusively through the aortic root. In Group I1 patients, a cardioplegia administration catheter (14F Argyle LV sump vent catheter) and a pressure-monitoring catheter (Argyle Medicut sentinel line catheter 2.3 mm in outer diameter) were inserted into the right atrium (Fig 1).An initial dose of cardioplegia (250 to 300 ml) was given through the aortic root to achieve diastolic arrest [18]. The remainder of the first dose and the ensuing doses of cardioplegia were administered through the right atrium with the pulmonary artery clamped and the cavae snared. Right atrial pressures were monitored during cardioplegia administration and were maintained lower than 40 mm Hg. In all patients, temperatures were measured in the LV apex and RV free wall. Enough cardioplegia (2 to 3 liters) was given to lower LV temperatures to 18°C or less. Distal anastomoses were finished first. In Group I, the completed vein grafts were intermittently perfused with cardioplegia. In all patients, the vein grafts were perfused with systemic blood while the proximal anastomoses were constructed. After the proximal anastomoses were completed, reperfusion was continued for twenty minutes prior to weaning from cardiopulmonary bypass. Intraoperatively, catheters were placed in a radial artery and in the right atrium, and a balloon-tipped catheter was positioned in the pulmonary artery for postoperative hemodynamic measurements. Postoperative Protocol Patients underwent volume loading with simultaneous radionuclide and hemodynamic studies on postoperative day 1 (20 hours postoperatively). Study patients were breathing spontaneously, remained intubated on 5 mm Hg constant positive airway pressure, and were sedated with intravenous administration of diazepam and morphine during the protocol. All patients were weaned from intravenously administered inotropic and pressor agents, and any volume deficits were corrected (pulmonary capillary wedge pressure [PCWP] 10 mm Hg or higher) prior to the study.

Fig 1. Techniqi~eof cannnlation and method for ndniinistering right atrial retrograde coronary sinus cardioplegia. Note that the ascending aorta is z w ~ t e dand right atrial pressures are inonitored during cnrdioplegia adrninistration. (CP = cardioplegia.)

During atrial pacing (100 beats per minute), simultaneous hemodynamic measurements and equilibriumgated radionuclide ventriculography were performed at baseline and following each of two volume loads. Each volume load was accomplished with 1,000 to 1,500 ml or crystalloid infused rapidly to raise the PCWP by 2 to 4 mm Hg. Hemodynamic measurements consisted of heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, mean right atrial pressure, mean PCWP, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, mean pulmonary artery pressure, and thermodilution cardiac output. Serial gated radionuclide ventriculograms were performed with in vivo red blood cell labeling with 15 to 25 mCi of technetium 99m (''"'Tc) following intravenous injection of stannous pyrophosphate. Radionuclide ventriculograms were obtained using an Anger scintillation camera with a 250 caudally angulated slant-hole straightbore collimator. Data acquisition was gated to the ECG with the cardiac cycle divided into 24 frames. Images were acquired and processed on a dedicated nuclear medicine computer using a 15% window centered about the ""'Tc photopeak. Radionuclide ventriculograms were analyzed using previously described techniques [19-221 with LVEFs and RVEFs calculated as end-diastolic counts - end-systolic countdend-diastolic counts following background subtraction. Stroke index (SI) was derived from the thermodilution

597 Diehl et al: Retrograde Coronary Sinus Cardioplegia

cardiac index (CI) and heart rate (HR) by the relationship: SI

=

CI/HR.

The stroke index and the radionuclide EF were used to derive end-diastolic volume index (EDVI): EDVI

=

SI/EF.

The end-systolic volume index (ESVI) was calculated from the formula: ESVI

=

EDVI

-

SI

Stroke work index (SWI) was calculated as follows: LVSWI

RVSWI

=

(MSBP - PCWP) x S1 x 0.0136 (MPSP - RAP) X SI X 0.0136

where MSBP = mean systolic blood pressure, MPSP = mean pulmonary artery systolic pressure, and RAP = right atrial pressure [23]. Volumes derived from the thermodilution stroke index correlated well with volumes derived from the radionuclide ventriculograms. Myocardial performance was assessed by comparing derived SWI with EDVI. Systolic function was evaluated by relating end-systolic blood pressure to ESVI. Diastolic function was evaluated by comparing the natural logarithm of the PCWP with the EDVI [24].

Stat is tical Analysis Statistical analysis was performed with the Statistical Analysis System programs (SAS Institute Inc., SAS Circle, Box 8000, Cary, NC). Analysis of covariance was assessed to analyze the pressure-volume relationships, and the paired t test was used to assess changes in hemodynamic variables induced by volume loading. Variables are summarized as the mean & the standard error of the mean in the table and figures.

Results Preoperative and intraoperative patient data are given in the Table. Patients in both groups were similar with respect to age, sex, preoperative ventricular function, completeness of revascularization, cross-clamp time, and duration of cardiopulmonary bypass. Infusion times for cardioplegia administration were similar in both groups. However, Group I1 patients received an average of 500 ml more cardioplegia than Group I patients. Intraoperative mean myocardial temperatures as measured in the LV apex and RV free wall were similar in both groups ( p = 0.11 and p = 0.20, respectively). Temperature data are illustrated in Figure 2. Low cardiac output syndrome (inotropic agents and an intraaortic balloon pump required for weaning from cardiopulmonary bypass) occurred in 1 patient in Group 11. The patient was weaned from both the intraaortic balloon

Suinrnar!~of Patient Dntn" Group I

Group I1

Variable

(ARC)

(RCSC)

Age (yr) Age range (yr)

58 +- 5 45-65 911 0/7/3 4110 8110 1/10

58 2 7 49-76 911 1/7/2 6/10 7110 1/10

49 2 13 125 ? 24 51 -+ 6

48 ? 7 113 t 13 49 ? 6

Sex (MIF) No. of grafts per patient (4/3/2) Left main lesion (>75%) Internal mammary artery

Thromboendarterectomy of right coronary artery

Clamp time (min) Duration of CPB (min) Preoperative LVEF (70)

"Where applicable, data are shown a s the mean t the standard error of the mean. ARC = aortic root cardioplegia; RCSC = retrograde coronary sinus cardioplegia; CPB = cardiopulmonary bypass; LVEF = left ventricular ejection fraction.

pump and the inotropic agents prior to volume loading on the first postoperative day. Postoperatively there were no deaths, and the hospital stays were similar in both groups (7 ? 0.7 days). One patient in Group I1 sustained a perioperative myocardial infarction (new Q waves on ECG). The impact of volume loading on right atrial pressure, PCWP, mean arterial pressure, mean pulmonary artery pressure, and EDVI is shown in Figures 3 and 4. Both right atrial pressure and PCWP increased with volume loading (p < 0.005) (see Fig 3 ) . Mean arterial pressure, mean pulmonary artery pressure (see Fig 3), and EDVI (see Fig 4) also increased with volume loading. All of these changes were similar in Group I and Group I1 patients.

Ejection Fraction Volume loading produced increases in EF that were similar in both groups of patients. These changes occurred with similar preload and afterload conditions in both groups at baseline and after volume loading. EFs derived from preoperative radionuclide ventriculograms are compared with baseline (before volume loading, nonpaced) postoperative EFs in Figure 5. Mean arterial pressure and radionuclide-derived LVEDVI were similar in both groups preoperatively and postoperatively at baseline. The data reveal a significant increase in LVEF in Group I1 (p < 0.05) and no change in Group I. RVEFs were similar preoperatively and at baseline postoperatively in both groups. Myocardial Performance Myocardial performance curves for the left ventricle (LVSWI versus LVEDVI) are depicted in Figure 6. Increases in SWI due to increased LV diastolic volume were similar in both groups ( p = 0.86 by analysis of

598 The Annals of Thoracic Surgery

0GRP I

- 1 -Y

Vol 45 No 6 June 1988

lo

1

0GRP I

GRP II

T

2o

'5

w

a

3

2 a

10

W

P

I w I-

5

LV

RV

Fig 2. Myocardial temperatures (+ the standard error of the mean) during cross-clamping for Group I (aortic root cardioplegia) and Group I1 (retrograde coronary sinus cardioplegia) patients as ineasured in the left ventricular apex (LV) and right oentricular free ztiall (RV).

Fig 4. The change (+ the standard error of the mean) in end-diastolic volume index (EDVI) induced by volume loading for Group I and Group I1 patients. (LV = left ventricular apex; RV = right oentricular free wall.)

80

15 I

m

I

-

a z E!

T

3

In I n 5

YX

T

IW V

YX

W

r

a n

a -

PCW

60

50

7

W

0

TT

i

u

L

W

-l

E! I-

0GRP I 69 G R P I I

10

n

RV

LV

0

MABP

RAP

MPAP

Fig 3. Pressure changes (+ the standard error of the mean) induced by volume loading for Group I arid Group 11. The increase in right atrial pressure (RAP) and piilmonary capillary zuedge pressure (PCW) over baseline is significant (** = p < 0.005) (MABP = mean arterial blood pressure; MPAP = meat1 pulmonary artery pressure. )

covariance). RV performance curves (RVSWI versus RVEDVI) are illustrated in Figure 7. There is a trend toward improved RV performance for Group I1 (RCSC) versus Group I (ARC) (Group I curve depressed relative to Group I1 curve), although the difference did not attain significance ( p = 0.60 by analysis of covariance) with the small number of patients studied. LV Systolic Performance The relationship of end-systolic blood pressure to LVESVI is shown in Figure 8. There were no significant differences between the groups ( p = 0.74 by analysis of covariance). LV Diastolic Performance The relationship between pressure and diastolic volumes for the left ventricle is plotted in Figure 9 as the natural logarithm of the PCWP versus the LVEDVI [24]. There were no differences between the groups ( p = 0.99 by analysis of covariance).

an .-

PreOp POItOP

PreOP POIIDP

P r M p POSIOP

preop P o I I o p

LV

LV

RV

RV

Fig 5. Ejection fractions (EF) (2 the standard error of the mean) preoperatively versus postoperatively for the left ventricular apex (LV) and the right ventricular free wall (RV). Note that there is a significant, (* = p < 0.05) increase in LVEF postoperatively in patients in Group I1 (retrograde coronary sinus cardioplegia).

Comment Inadequate perfusion of regional myocardium beyond obstructed or stenotic coronary arteries is a recognized inadequacy of ARC [4, 7, 91. Delivery of cardioplegia through the non-obstructed coronary veins experimentally produces superior cooling and postoperative function in regional myocardium beyond obstructed coronary arteries [8, 121. Clinical studies with temperature mapping by thermographic analysis have demonstrated more uniform ventricular cooling with RCSC compared with ARC [25]. Although well suited as a method of myocardial protection in patients with coronary artery disease, RCSC by direct cannulation of the coronary sinus is technically cumbersome and can result in damage to the atrioventricular node and the sinus [15]. Also, there is concern that the RV free wall and septum may be inadequately perfused with this technique because of anatomical patterns of venous drainage [I61 and obstruction of proximal coronary veins by the coronary sinus balloon catheter [5]. Right atrial RCSC obviates direct cannulation of the sinus, is a simple technique to employ, and overcomes many of the concerns regarding right heart preservation

599 Diehl et al: Retrograde Coronary Sinus Cardioplegia

-

N

E

\

-

55

C.

50

-

150 i GRP I

T

GRPII

T

/

-

!q

5

b

I4O1 130

0--9

120

J

""

I

55

60

LVEDVI ( rnl / m 2 Fig 6. The relationship between left ventricular stroke work index (LVSWI) and left ventricular end-diastolic volume index (LVEDVI). N o significant difference is noted between Groups Z and ZI. All points denote values ? the standard error of the mean.

-

N

€

\

-

I

6

T

C.

34

Fig 8. The relationship between end-systolic blood pressure (ESBP) and left ventricular end-systolic volume index (LVESVI) for Groups I and ZI. This relationship is similar for both groups. All points denote values ? the standard error of the mean.

GRP I GRP II

15

-

14

-

13 -

I

k

GRPII

LVESVI ( r n l / m * )

E

v

29

24

70

65

GRP I

5

0

I

E E

E

12

-

II

-

10

GRP I

3

55

60

65

70

RVEDVI ( ml/rn2)

Fig 7. The relationship between right ventricular stroke work index (RVSWI) and rixht ventricular end-diastolic volume index (RVEDVI). Therelationship for Group Z (aortic root cardioplegia) patients is depressed relative to that for Group ZI (retrograde coronary sinus cardioplegia) patients. However, there are no significant differences between groups. All points denote values ? the standard error of the mean.

[16]. This method does, however, violate one of the basic principles of myocardial protection by inducing RV distention in the arrested heart [26-281. Also, despite the interest in RCSC for aortic valve operations, data regarding the efficacy of this mode of cardioplegia delivery in preserving LV function following CABG are lacking. This study was designed to compare postoperative ventricular function in two groups of patients undergoing CABG: those operated on with right atrial RCSC and those operated on with standard ARC. Ventricular function was assessed with the use of postoperative volume loading combined with simultaneous nuclear ventriculography and thermodilution cardiac output data. This protocol has been described and repeatedly utilized in clinical studies by Weisel and colleagues [29, 301. Radionuclide ventriculography provides accurate estimates of ventricular EFs. Ventricular volumes are derived from

8

MGRP II

I

55

60

65

70

LVEDVI ( rnl/rn2)

Fig 9. The relationship between the natural logarithm of pulmonary capillary uiedge pressure (LnPCW) and left ventricular end-diastolic volume index (LVEDVI) for Groups Z and I I . This relationship is similar for both groups. All points denote values ? the standard error of the mean.

the thermodilution stroke index because nuclear ventriculography provides less accurate estimates of ventricular volumes, particularly of the right ventricle [22]. When analyzing postoperative pressure-volume relationships and ventricular function curves, the analysis of covariance is used to assess the position and slope of the various curves, thereby permitting comparisons between groups. The temperature data reveal that both methods produce sufficient and similar cooling of the left and right ventricles (see Fig 2). Because temperatures were measured in only one area in both ventricles in these patients, it is not known whether RCSC produced more uniform cooling than ARC, as has been demonstrated by Shapira and associates [25]. The radionuclide-derived EFs for the left ventricle reveal a significant improvement in Group I1 (RCSC)

600 The Annals of Thoracic Surgery

Vol45 No 6 June 1988

patients and no change in Group I (ARC) between preoperative and baseline postoperative measurements. RVEFs did not change postoperatively in either group (see Fig 5). The EF is sensitive to both preload and afterload. If one uses arterial blood pressure as a reflection of afterload and radionuclide-derived EDVI as an indicator of preload for the left ventricle, both groups are closely matched preoperatively and at baseline postoperatively. RV loading conditions are unknown preoperatively. However, because loading conditions were not critically studied in patients preoperatively, it is difficult to assess changes in ventricular function using only these data. The postoperative pressure-volume relationships are more informative. The LV performance curves relate changes in ventricular volume at end-diastole (preload) to work performed (stroke work). The curves for both groups are similar (see Fig 6). The end-systolic pressure-volume relationship is not preload sensitive and utilizes afterload. The slope of the relationship is thought to reflect ventricular contractility [31-331. The LV end-systolic pressure-volume relationships for both groups are also similar (see Fig 8). The diastolic pressure-volume relationships are plotted as the natural logarithm of the PCWP versus the EDVI for the left ventricle (see Fig 9). The slope of this linear relationship reflects diastolic stiffness. These plots are similar for both groups. The RV performance curves are also similar for both groups (see Fig 7). These curves, however, are not as closely related as are those for the left ventricle. The curve for Group I patients is depressed relative to that for Group I1 patients, thereby indicating a lower developed stroke work at similar RVEDVI. The trend toward better RV function in Group I1 (RCSC) patients might have achieved significance with more study patients. The effect of RCSC on RV postoperative function is currently being investigated further in our laboratory. The excellent clinical results in this study were obtained in a relatively small sample of patients with normal LV function. The technique of RCSC through the right atrium is currently being evaluated in patients with impaired ventricular function and in acutely ischemic patients. Further clinical trials are necessary to better define the role of RCSC as a method of myocardial protection.

Conclusion Retrograde coronary sinus cardioplegia administered through the right atrium results in intraoperative LV and RV cooling and preservation of postoperative LV function equivalent to that attained with conventional ARC. Despite ventricular distention, right atrial RCSC does not impair postoperative RV function when RV pressures are maintained at less than 40 mm Hg during cardioplegia administration [26]. The right atrial technique of RCSC is easy to employ and may be advantageous in the following situations:

When ARC results in insufficient ventricular cooling because of a tight left main lesion or severe threevessel coronary artery disease. As an alternative to direct coronary artery ostial cannulation for aortic valve procedures or in patients with aortic insufficiency undergoing CABG. For mitral valve operations where repeated doses of ARC could result in coronary air embolism and necessitate the removal of air from the aortic root.

This work was performed during Dr. Eichhorn’s tenure as a Research Fellow of the American Heart Association, Massachusetts Affiliate.

References 1. Blanco G, Adam A, Fernandez A: A direct experimental approach to the aortic valve: 11. Acute retroperfusion of the coronary sinus. J Thorac Surg 32171, 1956 2. Gott VL, Gonzalez JL, Zuhdi MN, et al: Retrograde perfusion of the coronary sinus for direct vision aortic surgery. Surg Gynecol Obstet 104:319, 1957 3. Lillehei CW, DeWall RA, Gott VL, Varco RL: The direct vision correction of calcific aortic stenosis by means of a pump-oxygenator and retrograde coronary sinus perfusion. Dis Chest 30:123, 1956 4. Davies AL, Hammond GL, Austen WG: Direct left coronary artery surgery emptying retrograde perfusion of the coronary sinus. J Thorac Cardiovasc Surg 54:848, 1967 5. Menaschk P, Kural S, Fauchet M, et al: Retrograde coronary sinus perfusion: a safe alternative for ensuring cardioplegic delivery in aortic valve surgery. Ann Thorac Surg 34:647, 1982 6. Fuentes M, Batanero J, Robles D, et al: Cardioplegia via the coronary sinus: our experience in 331 cases. In Mohl W, Wolner E, Glogar D (eds): The Coronary Sinus. New York, Springer-Verlag, 1984, p p 316319 7. Hilton CJ, Teubl W, Acker M, et al: Inadequate cardioplegic protection with obstructed coronary arteries. Ann Thorac Surg 28:323, 1979 8. Gundry SR, Kirsh MM: A comparison of retrograde cardioplegia versus antegrade cardioplegia in the presence of coronary artery obstruction. Ann Thorac Surg 38:124, 1984 9. Mori F, Ivey T, Tabayashi K, et al: Regional myocardial protection by retrograde coronary sinus infusion of cardioplegic solution. Circulation 74:Suppl 3:116, 1986 10. Solorzano J, Taitelbaum G, Chiu RC-J: Retrograde coronary sinus perfusion for myocardial protection during cardiopulmonary bypass. Ann Thorac Surg 25:201, 1978 11. Masuda M, Yonenaga K, Shibi K, et al: Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs: preservation of high-energy phosphates and regional function. J Thorac Cardiovasc Surg 92:255, 1986 12. Horneffer PJ, Gott VL, Gardner TJ: Retrograde coronary sinus perfusion prevents infarct extension during intraoperative global ischemic arrest. Ann Thorac Surg 42:139,1986 13 Becker H, Vinten-Johansen J, Buckberg GD, et al: Critical importance of ensuring cardioplegic delivery with coronary stenoses. J Thorac Cardiovasc Surg 81:507, 1981 14 Vander Salm TH, Okike ON, Cutler BS, et al: Improved

601 Diehl et al: Retrograde Coronary Sinus Cardioplegia

15.

16. 17.

18.

19.

20.

21.

22.

23. 24.

25. 26.

27.

28.

29. 30. 31.

32.

myocardial preservation by improved distribution of cardioplegic solutions. J Thorac Cardiovasc Surg 83:767, 1982 Fabiani JN, Relland J, Carpentier A: Myocardial protection via the coronary sinus in cardiac surgery: comparative evaluation of two techniques. In Mohl W, Wolner E, Glogar D (eds): The Coronary Sinus. New York, Springer-Verlag, 1984, pp 305-311 Shiki K, Masuda M, Yonenega K, et al: Myocardial distribution of retrograde flow through the coronary sinus of the excised normal canine heart. Ann Thorac Surg 41:265, 1986 Fabiani J-N, Deloche A, Swanson J, Carpentier A: Retrograde cardioplegia through the right atrium. Ann Thorac Surg 41:101, 1986 Lomeo A, Battaglia G, Carli L, et al: Myocardial protection: anterograde versus retrograde cardioplegia: a clinical trial on 145 patients. In Mohl W, Wolner E, Glogar D (eds): The Coronary Sinus. New York, Springer-Verlag, 1984, pp 312-315 Maddow DE, Holman BL, Wynne J, et al: Ejection fraction image: a non-invasive index of regional left ventricular wall motion. Am J Cardiol 41:1230, 1978 Holman L, Wynne J, Idoine J, et al: The paradox image: a non-invasive index of regional left ventricular dyskinesis. J Nucl Med 20:1237, 1979 Konstam MA, Wynne J, Holman BL, et al: Use of equilibrium (gated) radionuclide ventriculography to quantitate left ventricular output in patients with and without leftsided valvular regurgitation. Circulation 64:578, 1981 Konstam MA, Kahn PC, Curran BH, et al: Equilibrium (gated) radionuclide ejection fraction measurement in the pressure- or volume-overloaded right ventricle: comparison of three methods. Chest 86:681, 1984 Gorlin R, Messer JV, Levine HJ, et al: Coronary circulation in health and disease. Med Clin North Am 44(18):1181,1960 Gaasch WH, Cole JS, Quinones MA, Alexander JK: Dynamic determinants of left ventricular diastolic pressurevolume relations in man. Circulation 51:317, 1975 Shapira N, Lemole GM, Spagna PM, et al: Antegrade and retrograde infusion of cardioplegia: assessment by thermovision. Ann Thorac Surg 43:92, 1987 Mihaileanu S, Fabiani JN, Jolven J, et al: A comparative study between antegrade cardioplegia and retrograde cardioplegia using intra-operative myocardial contrast echography. In Mohl W (ed): Clinics of Coronary Surgery Interventions. New York, Springer-Verlag, 1986, pp 235-240 Pennock JL, Pierce WS, Waldhausen JA: Quantitative evaluation of left ventricular bypass in reducing myocardial ischemia. Surgery 79:523, 1976 Olinger GN, Bonchek LI: Ventricular venting during coronary revascularization: assessment of benefit by intraoperative ventricular function curves. Ann Thorac Surg 26:525, 1978 Mullen JC, Fremes SE, Weisel RD, et al: Right ventricular function: a comparison between blood and crystalloid cardioplegia. Ann Thorac Surg 43:17, 1987 Weisel RD, Burns RJ, Baird RJ, et al: Optimal postoperative volume loading. J Thorac Cardiovasc Surg 85:552, 1983 Mehmel HC, Stockus B, Ruffman K, et al: The linearity of the end systolic pressure volume relationship in man and its sensitivity for assessment of left ventricular function. Circulation 63:1216, 1981 Borow KM, Newmann A, Wynne J: Sensitivity of end systolic pressure dimension and pressure volume relations to the inotropic state in humans. Circulation 65:988, 1982

33. McKay RG, Aroesty JM, Heller GV, et al: Left ventricular pressure volume diagrams and end systolic pressure volume relations in human beings. J Am Coll Cardiol 3:301, 1984

Discussion (Lancaster, PA): I appreciate the opportunity to discuss this very elegant, thought-provoking paper that should prompt each of us to reassess our approach to myocardial protection. In patients who require operation for valvular heart disease or ascending aortic aneurysms, anterograde cardioplegic arrest combined with topical hypothermia is almost universally employed as the routine method of myocardial protection. In our practice, we emphasize effective topical hypothermia with a myocardial jacket for valve procedures, and since we are thereby assured that myocardial temperature can be maintained at 8" to 12"C, we are content to infuse cardioplegia only once for ischemic intervals up to seventy five minutes. This has been particularly advantageous for mitral valve repair. The technique of RCSC provides a useful alternative method of protection in certain of these patients with valvular disease who are ill suited for anterograde infusion, such as patients with aortic regurgitation and extensive calcification surrounding the left coronary orifice. However, since this study focused on CABG, I will limit my remarks to CABG also. Our effort has been to achieve simplicity and safety in CABG operations and to avoid potentially cumbersome methods that prolong the operation. We have also been aware that cardioplegia is often inherently ill suited for CABG and is usually unnecessary, since the required ischemic intervals are short. Cardioplegia has a number of disadvantages: occluded coronary arteries or patent internal mammary arteries or both impair the distribution of cardioplegia, noncoronary collateral flow washes out cardioplegia during the operation and rewarms the heart, any changes in the operative plan inevitably prolong the ischemic period, and perioperative arrhythmias are common. From the beginning of our program in Lancaster in September, 1983, until June, 1987, 1,300 patients had coronary bypass with intermittent ischemia. This is an unselected series, excluding only patients who required valvular heart procedures or who had reoperations. The average age was 63 years, and the average number of grafts was 3 1/2 per patient. Thirty-six percent of the patients had elective operations, 44% had urgent operations, and 20% had emergency operations, CABG within 24 hours of catheterization. Two percent had had streptokinase less than 24 hours before operation, 5% had had percutaneous transluminal coronary angioplasty within 24 hours, and 3.5% had an intraaortic balloon pump preoperatively. In the elective and urgent categories, mortality was 0.67% (7 deaths among 1,048 patients), and in the emergency category, mortality was 2.4% (6 deaths among 252 patients), for an overall mortality of 1%. Of our patients, 2.3% had a perioperative infarction, 1.7% had low cardiac output, which we define as any use of intravenously administered inotropic agents other than digoxin, and 0.7% required an intraaortic balloon pump that was not in place preoperatively. I emphasize that despite our satisfaction with the noncardioplegia technique for routine operations, cardioplegia and particularly retrograde cardioplegia may have specific advantages in the patient with an acute coronary occlusion, such as after percutaneous transluminal coronary angioplasty, in whom we wish to control the conditions of reperfusion. In such patients, DR. LAWRENCE I . BONCHEK

602 The Annals of Thoracic Surgery

Vol 45 No 6 June 1988

it is not possible to use an internal mammary artery unless one first attaches a vein, reperfuses the ischemic area, and then substitutes that artery. Retrograde cardioplegia allows lowpressure reperfusion without interfering with internal mammary artery grafting. Would the authors agree that acute coronary occlusion is a situation in which retrograde cardioplegia is especially appealing? I wonder if the authors intend to carry out studies in a higher-risk subset of patients, since in the low-risk group they studied, it was possible only to prove that retrograde cardioplegia was no worse than anterograde cardioplegia; they could not prove its superiority. Finally, would it be better to call this retrograde transatrial cardioplegia rather than RCSC? D R . GERARD M . GUIRAUDON (London, Ont, Canada): I congratulate the authors for their nice presentation, and I endorse their view. My colleagues and I have published a study of 40 patients in which we compare retrograde coronary sinus perfusion and aortic perfusion in CABG procedures. Our study showed a similar trend in favor of retrograde coronary sinus perfusion. I have two questions for the authors. First, why did they use retrograde atrial perfusion, which may be associated with overdistention of the right atrium and right ventricle and may damage the right ventricle? We perfuse the coronary sinus using a 16F Foley catheter secured by a pursestring suture around its orifice. We observed neither injury to the coronary sinus nor atrioventricular conduction disturbances. Second, do the authors think that injection of some cardioplegia into the aortic root as an initial dose makes the comparative study less valid?

DR. GREGORY A. MISBACH (Seattle, WA): I commend the authors for showing us the ease with which retrograde cardioplegia can be used. In the past year, my associates and I have published data from our laboratory that show there is better temperature reduction and better regional myocardial function in an area distal to an acute coronary occlusion. We have subsequently used RCSC in select patients in whom it is difficult to achieve good ARC, for example, patients with aortic insufficiency. In mitral valve replacements, it is not much of an additional step to open the right atrium, after you have double-cannulated the venae cavae, insert a Foley catheter in the coronary sinus, and achieve very good cardioplegia. I think that the questions raised about acute occlusion after percutaneous transluminal coronary angioplasty help identify a subset of patients in whom it is difficult to achieve good cardioplegia distal to acute occlusion and in whom use of retrograde cardioplegia would achieve better production by better temperature reduction when there is not good collateral flow into that area. My question is the same as one previously asked. Why not

insert a Foley catheter directly into the coronary sinus rather than distend the entire right atrium and right ventricle?

I thank the discussants for their kind comments. Dr. Bonchek, we also acknowledge the importance of topical cooling and utilize it in all of our patients, both with retrograde cardioplegia and ARC. Right atrial retrograde cardioplegia is particularly well suited to redo operations, especially in light of the fact that grafted native coronary vessels are frequently occluded and old saphenous vein grafts, in addition to being stenotic, frequently contain friable particulate matter that can embolize during aortic cardioplegia administration. We are currently using this technique in a higher-risk subset of patients, including patients undergoing CABG after failed percutaneous transluminal coronary angiopiasty. RV function is being carefully looked at both in the laboratory and in the clinical setting. We think that in a higher-risk group of patients, the retrograde delivery of cardioplegia will demonstrate multiple advantages over conventional ARC. Dr. Guiraudon, the right atrial approach for delivery of retrograde cardioplegia has several theoretical as well as practical advantages over direct coronary sinus perfusion. Once the right atrial technique is mastered, it is quite simple to implement. It avoids a right atriotomy and avoids the potential complications of atrioventricular block and coronary sinus rupture. In addition, since the right ventricle and a portion of the septum drain directly into the ventricular cavity through thebesian veins and since a balloon catheter in the coronary sinus may occlude several of the large proximal venous branches draining the right heart, there may be advantages to administering the cardioplegia directly into the ventricular cavity. Although RV distention is induced in an arrested heart, this does not impair RV function, as we have demonstrated. Our data also suggest that right atrial cardioplegia may result in better RV function than ARC. This issue is currently being pursued in more depth in the animal laboratory. The initial aortic root dose of cardioplegia was given to achieve rapid diastolic arrest. When retrograde cardioplegia is utilized alone, it takes four to five minutes to achieve diastolic arrest. The initial dose of 200 to 250 ml of ARC achieves rapid arrest and avoids a globally ischemic, fibrillating heart and the resultant depletion of high-energy phosphate stores. We recognize that we did not study the uniformity of cooling in these patients. It has been demonstrated clinically and experimentally that retrograde cardioplegia does achieve more uniform cooling than ARC, and I think this is a very important point. In performing any study on patients following a cardiac operation, the most difficult part is trying to assess ventricular performance. I take this opportunity to acknowledge the contributions of Dr. Richard D. Weisel, my former teacher, and his colleagues in establishing the techniques utilized in our study. Through the many meticulous studies they have published in the past, they have made their techniques a standard. DR. DIEHL: