Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting

Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting

J THoRAc CARDIOVASC SURG 1989;97:715-24 Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myoca...

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THoRAc CARDIOVASC SURG

1989;97:715-24

Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting Myocardial hypothennia with multidose cardioplegia has not been compared with single-dose cardioplegia and myocardial surface cooling with a cooling jacket in patients having coronary artery bypass grafting. In this study, 20 patients with three-vessel disease undergoiilg coronary bypass at 28° C with bicaval cannulation, caval tapes, and pulmonary artery venting (4.9 ± 0.7 grafts per patient) were prospectively randomized equally into group I (multidose cardioplegia) and group II (single-dose cardioplegia with a coolingjacket). The initial dose of cardioplegic solution was 1000 mL Group I then received 500 mI of cardioplegic solution every 20 minutes, delivered into the aortic root and available grafts. In group II, after the cardioplegic solution had been administered, a cooling jacket covering the right and left ventricles was applied. In both groups temperatures were recorded every 30 seconds at five ventricular sites: (1)right ventricularepicardium;(2)right ventricular myocardiumor cavity,7 mm;(3)left ventricular epicardium;(4)left ventricular myocardium or cavity, 15 mm; and (5) septum, 20 mm, Group mean temperatures at each site at various times were compared within each group and between the two groups by analysis of variance. Aortic crossclamp time was 60.3 ± 12.1 minutes in group I and 52.8 ± 7.3 minutes in group II (p = 0.12); cardiopulmonary bypass time was 103.7 ± 11.1 minutes in groupI versus87.7 ± 12.7 minutes in group II (p < 0.01).One minute after the cardioplegicsolution was initially given, temperatures betweengroups at each site were not statistically different,but left ventricular epicardialtemperatures within both groups were significantly higher than in the other four sites. Nineteen minutes after administration of the cardioplegicsolution, temperatures in group I at all sites were higher than in group II. Similarly, throughout the entire period of aortic crossclamping, mean temperatures (exceptleft ventricular myocardial site), maximum temperatures, and percentage of time all temperatures were 15° C or higher were greater in group I than in group II. The following conclusions can be reached: 1. Initial myocardial coolingwith 1000 mI of cardioplegicsolution is not significantly limited by coronary artery disease but is suboptimal (16° or 17° C) in the inferior left ventricular epicardium because of continualwarmingfrom the aorta and subdiaphragmatic viscera. 2. Without myocardial surface cooling, excessive external myocardial rewarming to 18° to 22° C occurs within 20 minutes at all sites after delivery of the cardioplegicsolution.3. Myocardial surface coolingis necessary to further cool the inferior left ventricularepicardium after cardioplegia and to enhance maintenance of myocardial temperatures at all sites at 15° C or less. 4. Use of single-dose cardioplegia with a cooling jacket permits shorter cardiopulmonary bypass times. 5. Continuous multisite temperature measurement enhances prevention of myocardial rewarming.

Pat O. Daily, MD, Barbara Jones, RN, BSHS, Theodore L. Folkerth, MD, Walter P. Dembitsky, MD, William Y. Moores, MD, and Robert T. Reichman, MD, San Diego, Calif.

From Sharp Memorial Hospital, San Diego, Calif. Read at the Fourteenth Annual Meeting of The Western Thoracic Surgical Association in Hawaii, June 22-25, 1988. Address for reprints: Pat O. Daily, MD, 8010 Frost St., Suite 501, San Diego, CA 92123.

Er the majority of patients undergoing coronary artery bypass grafting, hyperkalemic, hypothermic cardioplegia is the preferred method of myocardial protection.' The additive role of myocardial hypothermia to that of cardioplegia is widely recognized." At least in

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Fig. 1. Diagonal branch anastomosis . The patient's head is to the viewer's right. The left anterior descending anastomosis has been completed and the diagonal anastomosis is in progress. Essentially, all of the right and left ventricular surfaces are encompassed by the cooling jacket.

part because of myocardial rewarming, the hypothermic cardioplegic solution is frequently administered every 20 to 30 minutes (multidose cardioplegia).' Even so, significant myocardial rewarming to 20 C or more, arguably a level that represents suboptimal myocardial hypother• rrua, can occur. 5-8 The present study was undertaken to compare the effectiveness of maintenance of myocardial hypothermia with multidose cold blood cardioplegia to single-dose cold blood cardioplegia and myocardial surface cooling with a myocardial cooling jacket. 0

Patients and methods Patients. Twenty patients with three-vessel coronary artery disease, as defined by the Coronary Artery Surgery Study," were prospectively randomized into two equal groups. Group I consisted of patients undergoing coronary bypass with multidose cold blood cardioplegia. In group II patients, single-dose cold blood cardioplegia was followed by myocardial hypothermia with a cooling jacket. 10 Randomization criteria included the following: one or more planned grafts to each of the three major coronary arteries or, in the case of the circumflex, to a major branch of that artery; an ejection fraction of 50% or more; first time cardiac procedure; and coronary bypass grafting without associated procedures. Furthermore, no coronary endarterectomies were performed. Surgical methods. Standardization of the surgical procedure for both groups consisted of bicaval cannulation with the use of caval tapes and pulmonary artery venting for removal of the cardioplegic solution and pulmonary venous return blood. Perfusate temperature was maintained at 28 0 C during aortic

crossclamping . Immediately after aortic crossclamping in both groups I and II, 1000 ml of blood card ioplegic solution at 4 0 C was administered into the aortic root. The cardioplegic solution consisted of 1000 ml of electrolyte solution (Plasma-Lyte A) containing 50 mEq potassium chloride, 30 mEq magnesium sulfate , 30 gm 50% dextrose, and 75 mEq sodium bicarbonate. One part of this solution was then mixed with four parts of blood after institution of cardiopulmonary bypass with crystalloid prime. Potassium chloride was then added to result in 15 mEq of potassium chloride per liter of cardioplegic solution with a hematocrit value of 20% to 22%. Subsequently, group I patients received 500 mJ of cold blood cardioplegic solution every 20 minutes, which was simultaneously administered into the aortic root and available grafts. In group II, immediately after administration of cardioplegic solution, a cooling jacket covering the right and left ventricles was applied. Distal graft s were performed in the same sequence in both groups, with grafts to the right coronary system performed first followed by grafts to the circumflex and left anterior descending systems. For the right coronary system, exposure for grafts in the atrioventricular groove was obtained by moving the cooling jacket slightly toward the left ventricular apex. The opening in the cooling jacket was positioned over the posterior descending or posterolateral coronary arteries when those branches were being grafted . The obtuse marginal branches of the circumflex system, left anterior descending, and diagonal branches were also grafted through the jacket opening (Fig. 1). However, it was occasionally necessary to increase the jacket opening to allow access to the more posteriorly located obtuse marginal branches. Grafts to the circumflex artery proper were performed by opening the jacket in a U shape, lining the pericardiaI cavity, and displacing the heart anteriorly and to the right. Temperature measurements and statistical methods.

Volume 97 Number 5 May 1989

Cardioplegia during coronary bypass grafting

Vo r l .c l ' . I I

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Fig. 2. Temperature probes with metric scale. The shorter two have thermocouples at the tip a nd nea r the hub, a nd the longer septa l probe has a single thermocouple at the tip.

Table I. Group comparisons Group I: M DCP (n = 10)

Age (yr) CPS temp. in aortic root No. distal grafts Left internal thoracic artery grafts Aortic crossclamp time (min) CPB time (min) Maximum CK-MB (units) ECG evidence of new M J

67.1 ± 5.7 ± 4.9 ±

Group 1/: SDCP + CJ (n = 10)

65.5 ± 8.3 5.4 ± 2.3° C 4.9 ± 0.87 7 52.8 ± 7.7 87.7 ± 13.4 24.0 ± 8.0

8.0 1.5° C .73

3

60.3 ± 12.7 103.7 ± 11.7 47.9 ± 40.1

o

o

p Value

NS NS NS NS 0.12 <0.01

NS NS

Values are mean values with standard deviations. MD CP . Multidose blood cardioplegia; SDC P + CJ. single-dose blood cardioplegia with cooling jacket; CPS. cardioplegic solution; CPB. cardiopulmonary bypass. CK-MB. creatine kinase isoenzyme. ECG . electrocardiogram; MI. myocard ial infarction; NS . not significant.

Beginning 2 minutes before aortic crossclamping and continuing throughout, temperatures were recorded every 30 seconds with a computerized system* at five ventricular sites: (I) anterior right ventricular epicardium (R VE) , (2) right ventricular myocardium or cavit y at a depth of 7 mm (R VM) , (3) inferior left ventricula r epica rdium ( LVE ), (4) left ventricular myocard ium or cavity a t 13 mm (LVM), a nd (5) a pical septa l myocardium at 25 mm (S EP) as dep icted in Figs. 2 and 3. For each group mean temperatures at each site were ca lculated and compared at variou s tim es within each group and bet ween the two groups by repeated measures an alysis of variance. II Temperatures are presented as mean temperature with standard deviations of the ir respect ive group at each of the five sites. Co mparisons were perform ed j ust before , I minute a fter, and 19 minut es a fter delivery of the initial cardioplegic solution. Additiona lly, throughout the entire period of crossclamping, mean temperatures, ma ximum tem peratures reached, and percent of time temper atures equaled or exceeded 15 0 C were compa red. For group I, the total tem perature chang e and rate of temperature change between I minute and 19 minutes after delivery of the · Colc-Parmer 8109 Temper atur e Dat a Logger. Chicago. Ill.

ca rdioplegic solution were comp ared between sites within that group.

Results Group characteristics. Groups I and II were compared with respect to age, number of distal grafts, number of internal thoracic artery grafts, temperature of the cardioplegic solution as measured in the aortic root, cardiopulmonary bypass time, aortic crossclamp time, maximum elevation of myocardial band creatine kinase, and electrocardiographic evidence of new myocardial infarction in the postoperative period. These results are summarized in Table I. The only significant intergroup difference was less mean bypass time in group II-87.7 ± 12.7 minutes versus 103.7 ± 11.1 for group I (p < 0.01). Temperature measurements before, 1 minute after, and 19 minutes after administration of cardioplegic solution (Table II). Temperatures at each myocardial site were compared between the two groups and at each

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7 1 8 Daily et al.

except at the LVM site. At that site, group I mean temperature was 14.7° ± 1.5° C and group II was 13.2 ± 1.5° C, an insignificant difference. For the percent of time of aortic crossclamping that temperatures were 15° C or higher at all temperature sites, group I temperatures significantly exceeded those for group II (p < 0.049). Additionally, maximum temperatures reached during the period of aortic crossclamping at all temperature sites in group I exceeded those for group II (p < 0.009). Within group I the total change in temperature between 1 minute after the cardioplegic solution delivery was completed and 19 minutes later at each temperature site was not significantly different. Likewise, the rate of temperature change did not differ significantly at any of these five sites. Typical temperature curves for groups I and II are illustrated in Figs. 4 and 5, respectively.

Discussion

Fig. 3. Depiction of temperature probe locations. The right ventricular (RV) probe is placed anteriorly and the left ventricular (LV) probe inferiorly. The septal probe is irtserted at the left ventricular apex.

site within each group at three different time periods. The first time period was just before cardioplegic solution was given. There were no significant differences. One minute after completion of cardioplegic solution delivery, there were no significant intergroup temperature differences at specific sites, but temperature at the L VE site was significantly higher than at the other sites within each group. Nineteen minutes after completion of cardioplegic solution delivery, temperatures at all sites in group I were significantly higher than in group II. Temperature measurements throughout aortic crossclamping (Table III). Mean temperatures throughout the entire period of aortic crossclamping were compared between groups I and II and within each group at each temperature site, as were the maximum temperatures reached and the percent of time that temperatures were 15° C or higher. Mean temperatures throughout the crossclamp period in group II were significantly less than those for group I (p < 0.008),

Rationale of temperature monitoring. Although bicaval cannulation with the use of caval tapes should eliminate return of systemic venous blood, occasionally some leakage between the cannulas and caval tapes occurs. Therefore, a single probe for the right ventricle was fashioned with a thermocouple at 7 mm depth so that the thermocouple would be in or near the right ventricular cavity (RVM) to detect rewarming by systemic venous return. An additional thermocouple was placed near the hub of the same probe with insertion of the probe through the anterior aspect of the right ventricle (RVE) to detect rewarming from the operating room lights and air. Rewarming caused by pulmonary venous return which, in large part, represents bronchial return during bypass, was sensed by a thermocouple at 13 mm depth so that the thermocouple would be in or near the left ventricular cavity (L VM). This same probe incorporating a thermocouple near the hub to detect rewarming of the left ventricular epicardium from the adjacent aorta and subdiaphragmatic viscera was inserted into the left ventricular inferior wall (LVE). A thermocouple at 25 mm was used to measure temperature in the interventricular septum (SEP), since it was presumed that the septal region would be the most resistant portion of the myocardium to both initial cooling and subsequent rewarming. These probes and placement are illustrated in Figs. 2 and 3. Importance of myocardial hypothermia. Current clinical practice has established the fact that enhanced myocardial protection is obtained by the induction of cardiac arrest and hypothermia by hypothermic cardioplegic solution distributed via the coronary arteries

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Cardioplegia during coronary bypass grafting

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Table II. Temperature changes after CPS Group mean temperatures

Before CPS MDCP (n = 10) SDCP + CJ (n = 10) p Value 1 min after CPS MDCP (n = 10) SDCP + CJ (n = 10) p Value 19 min after CPS MDCP (n = 10) SDCP + CJ (n = 10) p Value

r C)

RVE

RVM

LVE

LVM

SEP

28.1 ± 2.3 27.0 ± 2.5 NS

29.2 ± 2.8 27.3 ± 2.5 NS

30.6 ± 2.2 29.7 ± 2.7 NS

30.0 ± 2.1 29.4 ± 2.7 NS

30.6 ± 2.7 29.1 ± 2.0 NS

11.3 ± 2.3 11.8 ± 3.2 NS

9.5 ± 2.0 10.6 ± 4.1 NS

16.5 ± 3.9 18.0 ± 3.2 NS

11.4 ± 2.7 14.1 ± 4.0 NS

11.8 ± 4.0 13.1 ± 5.6 NS

20.6 ± 3.0 12.8 ± 3.0 <0.001

18.6 ± 3.6 12.9 ± 2.7 <0.001

22.7 ± 2.2 13.5 ± 2.1 <0.001

18.1 ± 2.2 12.9 ± 1.4 <0.001

17.9 ± 2.6 12.8 ± 2.8 <0.001

Temperatures between the two groups are compared at specific time periods with respect to initial CPS: before CPS, I minute after CPS, and 19 minutes after CPS. All temperatures are in degrees Celcius with mean values and standard deviations. For abbreviations see Table I.

Table

m.

Temperature comparisons during aortic crossclamping Group mean temperatures

Mean temperatures MDCP (n = 10) SDCP + CJ (n = 10) p Value Maximum temperatures MDCP (n = 10) SDCP + CJ (n = 10) p Value % Time 2: 15° C MDCP (n = 10) SDCP + CJ (n = 10) p Value MDCP (n = 10) Total change Rate of change (OC/min) p Value

rC)

RVE

RVM

LVE

LVM

SEP

17.7 ± 1.5 12.1 ± 2.1 <.001

15.5 ± 1.6 12.4 ± 2.1 <.003

20.1 ± 1.8 11.8 ± 1.3 <.001

14.7 ± 1.5 13.3 ± 1.5 <.125

15.4 ± 3.2 12.7 ± 3.0 <.008

23.1 ± 1.7 15.7 ± 2.1 <.001

22.7 ± 3.5 15.2 ± 2.4 <.001

25.1 ± 2.1 18.2 ± 3.1 <.001

20.1 ± 1.7 16.6 ± 2.6 <.009

20.8 ± 3.7 15.4 ± 3.9 <.001

77.4 ± 12.9 17.3 ± 29.6 <.001

53.3 ± 14. 20.6 ± 29.6 <.004

94.7 ± 9.2 11.2 ± 9.0 <.001

42.0 ± 15.2 18.2 ± 22.2 <.029

53.6 ± 27.6 32.2 ± 37.9 <.049

8.6 ± 2.8 0.4 ± 0.2 NS

8.4 ± 2.6 0.4 ± 0.1 NS

7.2 ± 3.5 0.4 ± 0.2 NS

6.3 ± 3.7 0.3 ± 0.2 NS

5.6 ± 2.8 0.2 ± 0.1 NS

Temperatures between the two groups (except total temperature change and rate of change, which are for MDC? group only) are compared throughout the period beginning I minute after completion of the initial CPS to I minute before aortic crossclamp removal. All temperatures are in degrees Celcius with mean values and standard deviations. For abbreviations see Table I.

followed by maintenance of myocardial hypothermia with repeated administration of the solution and/or local myocardial hypothermia.t"" There is general but not complete agreement that it is desirable to maintain cardiac temperatures as much below 20° C as possible, provided that freezing is avoided." 7. 8.13-15 The use of saline slush is probably contraindicated because of potential myocardial damage" and phrenic nerve paresis.17• 19 In fact, Allen and co-workers" have suggested "topical cooling" is unnecessary and may be harmful. Several investigators''":" have advocated the use of topical hypothermia with cold saline. However, for coronary bypass grafting there is uneven distribution of

cold saline over the myocardium as different coronary branches are grafted and the operative field may be obscured. Rosenfeldt and Watson" have stated that the use of a cooling pad is not effective for coronary bypass. Consequently, multidose cold blood cardioplegia is frequently used for coronary bypass to maintain myocardial hypothermia and for whatever additional benefits may accrue from repeated delivery of the cardioplegic agent(s). Because of rewarming rates of 0.5° C per minute/l" or more, depending on systemic temperature," the present study was undertaken to compare the efficacy of maintenance of myocardial hypothermia with multidose cold blood cardioplegia given every 20

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40

GRAFTING SEQUENCE 1. LV br, of RCA 2. PO 3.0M1 4. Intermediate 5. LAD-LIMA

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a:

... W

10

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RVE

LVE

RVM

LVM

SEP

10 15 20 25 30 35 40 45 50 55 60 65 70 75

TIME (Min) Fig. 4. Temperature curves throughout aortic crossclamping with multidose cold blood cardioplegia in an illustrative case. The aortic crossclamp time was 77 minutes. LV. Left ventricular; RCA. right coronary artery; PD. posterior descending; OM. obtuse marginal; LAD-LIMA. left anterior descending-left internal mammary artery.

40

GRAFTING SEQUENCE

35

0

30

a:

W

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30

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TIME (Min) Fig. 5. Temperature curves throughout aortic crossclamping with single-dose blood cardioplegia with a cooling jacket in an illustrative case. DIAG. Diagonal branch. For other abbreviations see Fig. 4.

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minutes to that of a myocardial cooling jacket'? 19 which, if left partially open, can be positioned to perform distal anastomoses to any of the coronary arterial branches (Fig, 1). Adequacy of initial myocardial cooling by cardioplegic solution with coronary artery disease. Numerous authors have described inadequate myocardial cooling from the intraortic delivery of hypothermic cardioplegic solution in patients with coronary artery disease. This observation has been based on both experimentaF7-31 results and clinical assessments. 23,25,32-34 In fact, it has been suggested that multisite temperature measurement should be performed to establish the priority of coronary artery grafting to the warmer areas first.32, 33 In the current study, however, 1000 ml of cardioplegic solution at 4° C resulted in temperatures of 5.7° ± 1.5°C for group I and 5.4° ± 2.3°C for group II (p = NS*) at the site of delivery in the aortic root. This combination of cardioplegic solution volume and temperature was sufficient to cool all temperature sites in groups I and II to less than 15° C except for the LVE site. During administration of cardioplegic solution, portions of the right and left ventricles were in contact with the inferior and posterior pericardium. At that time cardiopulmonary bypass perfusate temperature was 28° C. This resulted in similar temperatures in the posteriorly located descending thoracic aorta and inferiorly situated abdominal viscera, which resulted in continual heat transfer to portions of the heart in contact with the pericardium. These anatomic relationships are illustrated in Fig. 6. During cardiopulmonary bypass with decompression of the right and left ventricles, greater contact of the ventricular myocardium with the adjacent structures may result than that shown in Fig. 6. This resulted in an LVE temperature of 16.5° and 18.0° C for group I and II, respectively. Similarly, Borst and Iversen"and Chiu and associates" reported less effective cooling of the posterolateral left ventricle with cardiaplegic solution. Consequently, in our subsequent experience, we have applied the cooling jacket before administering the solution to eliminate transpericardial heat transfer and, thereby, optimize myocardial cooling. We believe that bicaval cannulation, with caval tapes, is important to achieve maximum initial myocardial cooling for two reasons. First, as previously discussed, systemic venous blood, which is still relatively warm soon after the initiation of cardiopulmonary bypass, is prevented from entering the right side of the heart and *NS = Not significant.

Cardioplegia during coronary bypass grafting

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Fig. 6. The anatomic relationships of the subdiaphragmatic abdominal viscera and aorta to the left and right ventricles are illustrated as visualized in a magnetic resonance image in a sagittal-oblique projection. During cardiopulmonary bypass, with decompression of the right and left ventricles, greater contact of the ventricular myocardium with the adjacent structures may result. These relationships allow transpericardial heat transfer to the respective portions of the right and left ventricles unless an insulation and/or cooling device is interpositioned. Desc Ao, Descending aorta; RV, right ventricle; LV, left ventricle; LA, left atrium.

warming the right ventricle and the interventricular septum. Second, the cold cardioplegic solution, after passage through the coronary vasculature, exits the coronary sinus and is removed through the right ventricle into the pulmonary artery vent and results in additional internal cooling of the right ventricle and interventricular septum. Additionally, the pulmonary artery vent minimizes the return of pulmonary venous blood to the left side of the heart. Prevention of myocardial rewarming. If systemic and pulmonary venous return blood are controlled and minimized or eliminated as causes of internal cardiac rewarming," external heat transfer becomes relatively more important. Consequently, myocardial surface cooling is necessary for maintenance of myocardial hypothermia. Because of the difficulties of exposure for coronary anastomoses and adequate coverage of the ventricular surfaces with cold saline when the heart is displaced

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from the pericardial cavity, a cooling jacket was used. A standardized sequence of distal grafting (right, circumflex, left anterior descending) was utilized to enable temperature comparisons between groups I and II based on cardiac positioning. The left anterior descending system was grafted last to avoid subsequent displacement of the heart if an internal thoracic artery was the donor vessel. Evaluation of myocardial temperature at each site 19 minutes after the delivery of the cardioplegic solution was concluded reveals the effectiveness of myocardial surface cooling by the cooling jacket in preventing rewarming, as shown in Table II. After additional doses of cardioplegic solution, temperatures again rose to similar levels within 20 minutes in group I (Fig. 4) but remained relatively constant at 12 0 ± 2 0 C throughout the crossclamp period for group II (Fig. 5). Another advantage of single-dose cardioplegia with a cooling jacket, in addition to enhancement and maintenance of myocardial cooling, was the reduction of cardiopulmonary bypass time. In group II, bypass time was significantly less (87.7 ± 12.7 minutes) than in group I (103.7 ± 11.7 minutes,p < 0.01) because of the need to administer cardioplegic solution only once. Aortic crossclamp times were also less, but not significantly so (p = 0.12). Four patients in group I had internal thoracic artery grafts versus seven in group II (p = NS). This difference, though not significant, would tend to increase aortic crossclamp and bypass times for group II since, typically in our experience, internal thoracic artery grafts take a few minutes longer than saphenous vein grafts. Comment

We have found that 1000 ml of cardioplegic solution at 4 0 C is adequate in patients with three-vessel coronary artery disease to cool the right and left ventricular myocardium to 11 0 to 13 0 C, except for the inferior LVE, which remains warmer because of continual heat transfer fromt he descending thoracic aorta and subdiaphragmatic viscera. However, application of the cooling jacket before administration of cardioplegic solution eliminates this heat transfer and thereby allows more consistent myocardial cooling. Without continuous myocardial surface cooling after cardioplegic solution is administered, rewarming to 18 0 to 22 0 C from external heating occurs at all temperature sites, and especially the LVE site, within 20 minutes. If used after cardiaplegic solution, myocardial surface cooling is necessary to further cool the inferior left LVE and maintain myocardial temperatures at all sites at 13 0 ± 1 0 C. The

use of a cooling jacket, which must be repositioned after each distal anastomosis, did not extend cardiopulmonary bypass time but, rather, resulted in decreased bypass time by obviating the need for multidose cold blood cardioplegia. Continuous multisite temperature measurement permits monitoring of the adequacy of control of systemic and pulmonary venous return blood, as well as the effectiveness of the prevention of external rewarming. We would like to thank Elizabeth A. Gilpin, MS, Programmer Analyst at the University of California, San Diego, for her technical expertise in development of the statistical analyses. REFERENCES 1. Miller DW, Ivey TD,'Bailey WW, Johnson DD, Hessel EA. The practice of coronary artery bypass surgery. J THORAC CARDIOVASC SURG 1981;81:423-7. 2. Hearse DJ, Steward DA, Braimbridge MY. Cellular protection during myocardial ischemia: the development and characterization of a procedure for the induction of reversible ischemic arrest. Circulation 1976;54:193-202. 3. Roe BB, Hutchinson JC, Fishman NH, Ullyot DJ, Smith DL. Myocardial protection with cold, ischemic, potassium-induced cardioplegia. J THORAC CARDIOVASC SURG 1977;73:366-74. 4. Rosenfeldt FL, Hearse DJ, Cankovic-Darracott S, Braimbridge MY. The additive protective effects of hypothermia and chemical cardioplegia during ischemic cardiac arrest in the dog. J THORAC CARDIOVASC SURG 1980;79:29-38. 5. Harlan BJ, Ross 0, Macmanus Q, Knight R, Luber J, Starr A. Cardioplegic solutions for myocardial preservation: analysis of hypothermic rest, potassium arrest, and procaine arrest. Circulation 1978;58(Pt 2):1114-8. 6. Borst HG, Iversen S. Myocardial temperatures in clinical cardioplegia. Thorac Cardiovasc Surg 1980;28:29-33. 7. Conti YR, Bertranou EG, Blackstone EH, Kirklin JW, Digerness SB. Cold cardioplegia versus hypothermia for myocardial protection: randomized clinical study. J THO· RAC CARDIOVASC SURG 1978;76:577-89. 8. Swanson OK, Dufek JH, Kahn DR. Improved myocardial preservation at 4 0 C. Ann Thorac Surg 1980;30:51926. 9. Principal Investigators of CASS and their Associates. The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study. Circulation 1981;63(Pt 2):1-1-40. 10. Daily PO, Pfeffer TA, Wisniewski JB, et al. Clinical comparisons of methods of myocardial protection. J THORAC CARDIOVASC SURG 1987;93:324-36. 11. Winer BJ. Statistical principles and experimental design. New York: McGraw-Hill, 1971:514. 12. Lazar HT, Rivers S. Importance of topical hypothermia during heterogenous distribution of cardioplegia. J Am Coil Cardiol 1988;1l(suppl A):I72A. 13. Planz EJ Jr, Blackstone EH, Kouchoukos NT. Myocardial temperature gradients with cold cardioplegia during

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coronary artery surgery. Circulation 1980;62(Pt 2):I1I 323. 14. Krukenkamp I, Silverman N, Sorlie D, Pridjian A, Feinberg H, Levitsky S. Myocardial energetics after thermally graded hyperkalemic crystalloid cardioplegic arrest. J THORAC CARDIOVASC SURG 1986;92:56-62. 15. Takach TJ, Glassman LR, Milewicz AL, Clark RE. Continuous measurement of intramyocardial pH: relative importance of hypothermia and cardioplegic perfusion pressure and temperature. Ann Thorac Surg 1986;42:36571. 16. Speicher CE, Ferrigan L, Wolfson SK Jr, Yalav FH, Rawson AJ. Cold injury of myocardium and pericardium in cardiac hypothermia. Surg Gynecol Obstet 1962; 114:659-65. 17. Wheeler WE, Rubis LJ, Jones CW, Harrah JD. Etiology and prevention of topical cardiac hypothermia-induced phrenic nerve injury and left lower lobe atelectasis during cardiac surgery. Chest 1985;88:680-3. 18. Esposito RA, Spencer Fe. The effect of pericardial insulation on hypothermic phrenic nerve injury during open-heart surgery. Ann Thorac Surg 1987;43:303-8. 19. Daily PO, Dembitsky WP, Peterson KL, Moser KM. Modifications of techniques and early results of pulmonary thromboendarterectomy for chronic pulmonary embolism. J THORAC CARDIOVASC SURG 1987;93:22133. 20. Allen B, Rosenkranz E, Buckberg GD, et al. Topical cardiac hypothermia in coronary patients: an unnecessary adjunct to cardioplegic protection and cause of pulmonary morbidity. Circulation 1986;74(Pt 2):1179. 21. Bernhard WF, Schwarz HF, Mallick NP. Intermittent cold coronary perfusion as an adjunct to open heart surgery. Surg Gynecol Obstet 1960;111:744-8. 22. Rosenfeldt FL, Watson DA. II. Interference with local myocardial cooling by heat gain during aortic crossclamping. Ann Thorac Surg 1979;27:13-6. 23. 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. 24. Shumway NE, Lower RR, Stofer Re. Selective hypothermia of the heart in anoxic cardiac arrest. Surg GynecolObstet 1959;109:750-4. 25. Chiu RCJ, Blundell PE, Scott HJ, Cain S. The importance of monitoring intramyocardial temperature during hypothermic myocardial protection. Ann Thorac Surg 1979;28:317-22. 26. Juffe A, Burgos R, Montero CG, et al. Rewarming rate of the myocardium during aortic cross-clamp time: variations with different levels of body hypothermia. Texas Heart Inst J 1985;12:401-6. 27. Hilton CJ, Teubl W, Acker M, et al. Inadequate cardioplegic protection with obstructed coronary arteries. Ann Thorac Surg 1979;28:323-34. 28. Becker H, Vinten-Johansen J, Buckberg GD, Follette DM, Robertson JM. Critical importance of ensuring

Cardioplegia during coronary bypass grafting

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cardioplegic delivery with coronary stenoses. J THORAC CARDIOVASC SURG 1981;81:507-15. Grondin CM, Helias J, Vouhe PR, Robert P. Influence of a critical coronary artery stenosis on myocardial protection through cold potassium cardioplegia. J THORAC CARDIOVASC SURG 1981;82:608-15. Laschinger JC, Catinella FP, Cunningham IN Jr, Knopp FA, Nathan 1M, Spencer Fe. Myocardial cooling: beneficial effects of topical hypothermia. J THORAC CARDlOVASC SURG 1982;84:807-14. Heineman FW, MacGregor DC, Wilson GJ, Ninomiya J. Regional and transmural myocardial temperature distribution in cold chemical cardioplegia: significance of critical coronary arterial stenosis. J THoRAc CARDIOVASC SURG 1981;81:851-9. Daggett WM, Jacocks MA, Coleman WS, Johnson RG, Lowenstein E, Vander Salm TJ. Myocardial temperature mapping: improved intraoperative myocardial preservation. J THORAC CARDIOVASC SURG 1981;82:883-8. Fishman NH, Abouav J. Myocardial temperature differences as a guide to the order of coronary artery bypass anastomoses in high-risk patients. Am J Surg 1980; 140:92-8. Ekroth R, Berggren H, Sudow G, Wojciechowski J, Zackrisson BF, William-Olsson G. Thermographic demonstration of uneven myocardial cooling in patients with coronary lesions. Ann Thorac Surg 1980;29:341-5.

Discussion Dr. W. Gerald Rainer (Denver. Colo.). Daily and his co-workers have described their experiment using a wellplanned, prospective study, and the conclusions have been well elucidated and seem statistically sound. Appropriately, they emphasize the aspects of this topic other than myocardial temperature alone, which is important for a clinic or any group such as ours. They do emphasize in their manuscript the avoidance of overdistention by venting, the importance of insulating the myocardium against the warmer adjacent blood flow, and the ability to decrease the total pump and aortic crossclamp time with their methodology. It is critically important to realize that myocardial hypothermia is not synonymous with myocardial protection. The authors are careful not to leave any impression to the contrary in their manuscript. There are important considerations in myocardial protection other than temperature alone. Recent observations by several investigators have shown that even in the presence of myocardial hypothermia and temperatures under 15° C, myocardial pH begins to decrease rather dramatically after 1 hour of crossclamp time. This is only one area exemplifying the limitations to our understanding of myocardial protection. Dr. Daily, let me pose two or three questions, partly for clarification. I did not detect in your manuscript any mention of whether or not you use a warm perfusate near the end of the aortic crossclamp time. Dr. Daily. No, we have not done that in this series. We have done it in other cases. Dr. Rainer. Do you do that clinically in your other cases when they are not part of a series under investigation such as this one?

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Daily et al.

Dr. Daily. Not routinely. Typically, though, when we anticipate there has been some acute prior injury. Dr. Rainer. You did mention that there was not a statistical significance between the MB portion of CK, but I did not notice any other studies of left ventricular function in the early postoperative period. Dr. Daily. That is right. We did not do function studies, since the purpose of this study was strictly to evaluate consistency and degree of myocardial hypothermia with one method versus the other. Dr. Rainer. You were careful to point that out, and that was very appropriate. Just as a comment, the whole bottom line will be the long-term evaluation of left ventricular function. Dr. John Mullen (Toronto, Ontario, Canada). Dr. Daily, using myocardial surface cooling, you were able to maintain left ventricular temperatures between 10° and 15° C during most of the crossclamp period. In our clinical study of profound cardiac hypothermia, we found that intraoperative left ventricular temperatures below 10° C were associated with depressed postoperative ventricular function and metabolism. We believe that left ventricular myocardial temperatures should be maintained between 10° and 15° C, as you have achieved. I congratulate you on a fine study. Dr. W. R. Eric Jamieson (Vancouver, British Columbia, Canada). Like Dr. Rainer, I am concerned about myocardial metabolism and subsequent ventricular function. I would like to see you repeat the study and assess temperature, pH, and also ventricular function. It may be that you may not see these changes within just I hour of ischemia, but certainly extended procedures sometimes do require more than I hour of crossclamp time. Dr. Daily. In patients undergoing pulmonary thromboen-

The Journal of Thoracic and Cardiovascular Surgery

darterectomy, we have regularly extended the aortic crossclamp times for 2 hours and sometimes we approach 3 hours. I don't think we have ever been as short as 1 hour. It sounds like this would be an ideal subset of patients in which to do what you have suggested. Dr. Roger R. Ecker (Oakland, Calif). We have used various types of topical cooling along with blood cardioplegia. In many instances, and especially now that we are using more mammary arteries, we have been disturbed by the rate of left diaphragmatic paralysis. What is the incidence with this cooling jacket and are the results better than those obtained with topical hypothermia? Dr. Daily. The lower the systemic temperature, the greater the risk of phrenic nerve paresis with whatever kind of myocardial hypothermia being used. As mentioned before, we routinely lower the temperature to 20° C and use circulatory arrest during pulmonary endarterectomy. In those patients, who number approximately 100 now, we have seen no instance of phrenic nerve paresis. We have also used this approach in a large number of valve procedures, combined valve/coronary bypass operations, aortic root problems, and so forth, at 28° C systemic temperature without phrenic nerve paresis, so that has not been a problem so far. One possible factor helping to avoid phrenic nerve paresis is the presence of an insulator pad incorporated into the cooling jacket. In closing, this method does provide more consistent myocardial hypothermia. If you decide to use multidose cardioplegia without some sort of myocardial surface cooling, then, because of exterior rewarming from the aorta and the subdiaphragmatic viscera, it would make sense to use an insulator pad-that is, if you believe myocardial hypothermia is an important modality for myocardial protection.