R emerged as an attractive alternative for the delivery

Coronary Sinus Versus Aortic Root Perfusion With Blood Cardioplegia in Elective Myocardial Revascularization Andrew C. Fiore, MD, Keith S. Naunheim, MD, George C. Kaiser, MD, Vallee L. Willman, MD, Lawrence R. McBride, MD, D. Glenn P'ennington, MD, and Hendrick B. Barner, MD Department of Surgery, St. Louis University Medical Center and St. Marv's Health Center, St. Louis, Missouri The role of retrograde coronary sinus cardioplegia in patients undergoing elective coronary artery bypass grafting has not been fully defined. Forty patients undergoing coronary artery bypass grafting received either aortic root (2 patients) or coronary sinus (2 patients) cold potassium blood cardioplegia. The patients were similar with respect to age, ventricular function, severity of coronary artery disease, cross-clamp time, completeness of revascularization, frequency of internal mammary artery grafting, and mean infusate volume and temperature. The time required to deliver the initial dose of cardioplegic solution and the time to achieve arrest were prolonged in the coronary sinus group (p <.1 and p <.2, respectively). There were no differences between the two groups postoperatively with regard to enzymatic indices, heniodynamic measurement, or clinical outcome. Right ventricular function was preserved equally in both groups. We conclude that coronary sinus cardioplegia is a safe alternative to aortic root perfusion, but offers no advantage in elective myocardial revascularization. (Ann Tliorac Surg 1989;47:684-8) etrograde coronary sinus perfusion has recently re- R emerged as an attractive alternative for the delivery of cardioplegia. Experimental and clinical studies have documented its ability to achieve adequate preservation during global myocardial ischemia. Despite this evidence, the retrograde technique has not gained widespread use. Compared with aortic root cardioplegia () delivery, coronary sinus infusion can be associated with a delay in cardiac arrest, cumbersome infusion techniques, and the potential for inadequate right ventricular preservation. It is unclear which route of cardioplegia delivery is more advantageous clinically. The present study was undertaken to evaluate the efficacy of retrograde coronary sinus cardioplegia (RCSC) compared with standard in patients undergoing elective myocardial revascularization. Material and Methods Between January 1988 and May 1988, 4 patients undergoing elective coronary artery bypass grafting alternatively received cold blood cardioplegia either through the aortic root ( group, 2 patients) or through the coronary sinus (RCSC group, 2 patients). The protocol was approved by the institutional review board at St. Louis University Group Hospitals on September 26, 1988 (IRB No. 5287). Presented at the Thirty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 1-12, 1988. Address reprint requests to Dr Fiore, Department of Surgery, St. Louis University Medical Center, 3635 Vista Ave at Grand Blvd, PO Box 1525, St. Louis. MO 6311-25. Data recorded included age, sex, history of a transmural myocardial infarction, number of vessels bypassed, and frequency of internal mammary artery grafting. Regional wall motion abnormality was measured by left ventricular score as defined by The Coronary Artery Surgery Study [l]; left ventricular function was assessed also using left ventricular end-diastolic pressure. Major coronary artery stenosis was defined as occlusion of 5% or more of the left main trunk and 7% or more for all other coronary arteries in at least one view. Anesthesia management included endotracheal intubation and maintenance with fentanyl (2 to 5 pg/kg), pancuronium bromide (.1 mg/kg), and enflurane. Patients were ventilated with 1% oxygen. Catheters were placed in the radial artery, and a balloon-tip catheter was positioned in the pulmonary artery (Opticath P711; Oxymetric, Inc, Mountain View, CA) for hernodynamic measurements. Cardiopulmonary bypass was established using ascending aortic a d bicaval cannulation employing moderate systemic hypothermia (3 C nasopharyngeal temperature) and hemotlilution (2% to 25% hematocrit). The extracorporeal circuit contained a membrane oxygenator (SciMed model I-35-2A; SciMed Life Systems, Inc, Minneapolis, MN) primed with 1,8 ml of crystalloid and 5 ml of 5% albumin. In patients with retrograde infusion, the coronary *;inus was cannulated through a short right atriotomy. The composition of the infusate and the delivery were identical in both groups except for the route of delivery. Cardioplegia consisted of 4: 1 dilution of blood with.9% normal saline solution, which contained 2 meq/l of sodium bicarbonate. The initial dose was 1 ml/kg and 1989 by The Society of Thoracic Surgeons 3-4975/89/$3.5

Ann Thorac Surg 1989;476848 FIORE ET AL 685 Table I. Suminary of Patierit Data" Variable Age (yr) Age range (yr) Sex (male) Left ventricular score No. diseased vessels Left main No. vessels bypassed Internal mammary artery Duration of CPB (min) Cross-clamp time (min) RCSC P Group Group Value 66.4 2 1.7 53-77 11 6.9 2.8 2.9 2.7 3 3.9 2.23 13 128 2 5.6 76 2 4.9 68.1 2 1.7 5479 17 8.8 f.77 2.9 2.1 8 3.6 2.3 13 13? 4.3 78 -+ 6.1 'I Where applicable, data are shown as the mean -t the standard deviation. = aortic root cardioplegia; CPB = cardiopulmonary bypass; = not significant; RCSC = retrograde coronary sinus cardioplegia. contained 14 meq/l of KCI. Reinfusion (5 ml/kg) was performed at 2-minute intervals but contained only 6 meq/l of KCI. The patients received cardioplegia exclusively through the aortic root using a DLP catheter (DLP model 239; DLP, Walker, MI) at an infusion pressure of 8 to 1 mm Hg. The RCSC patients received cardioplegia exclusively through the coronary sinus using a DLP balloon-tip retrograde coronary sinus infusion catheter (DLP model 94-15) inserted through a small right atriotomy. Infusion pressure was maintained at 35 to 4 mm Hg. Topical myocardial cooling with lactated Ringer's slush and a cardiac insulation pad for phrenic nerve protection were employed in all patients. A left ventricular vent was not used. Distal anastomoses were constructed with aortic cross-clamping; proximal anastomoses were performed without global myocardial ischemia. The volume and temperature of the cardioplegic solution and the time required for infusion were recorded as were the interval to achieve cardiac arrest and the ventricular septal temperature (Shiley myocardial temperature probe DPM; Shiley Inc, Irvine, CA). Operative variables recorded included cardiopulmonary bypass and cross-clamp times, the number of trials necessary to separate the patient from the extracorporeal circuit, and the number of electric shocks required to achieve ventricular defibrillation. Blood samples for assessment of lactate dehydrogenase isoenzymes 1 and 2 (LDH, and LDH,) were obtained on postoperative days 1 and 2. A ratio between LDH, and LDH, that was 1. or greater was considered indicative of myocardial injury. Measurements of the myocardialspecific isoenzymes of creatine kinase were obtained before aortic cross-clamping and at 1, 2, 3, 4, 8, 12, and 24 hours after unclamping. A myocardial fraction higher than 5 U/L was considered diagnostic of myocardial injury. Hemodynamic measurements were obtained at.5, 1, 2, 3, 4, 8, 12, and 24 hours after cross-clamp removal. Measurements recorded included systemic, right atrial, pulmonary artery, and pulmonary capillary wedge pressures and cardiac output (thermodilution technique). Using standard formulas, values for cardiac index and right ventricular and left ventricular stroke work indices were calculated at identical intervals [2, 31. Data were analyzed using the Statview 512' statistical software package (Brainpower, Inc, Calabasas, CA). Univariate analysis of discrete variables was performed using,$ analysis or Fisher's exact test where appropriate. Student's t test was employed for continuous variables. A p value of.5 or less was considered significant. Mean values are expressed as plus or minus the standard deviation. Results The preoperative and intraoperative patient data are shown in Table 1. There were no differences between groups with respect to age, left ventricular function, severity of coronary artery disease, completeness of revascularization, frequency of internal mammary artery grafting, duration of extracorporeal circulation, or crossclamp time. The temperature of the infusate was approximately 5 C in all patients, and the mean ventricular septal temperature achieved was not different between the groups (, 1.7" f.5"c, and RCSC, 11." f.7"c; p = not significant []). Although a greater volume of cardioplegic solution was used in the group, the difference was not significant (1,767 f 117 versus 1,688 f 119 ml; p = ). The time required to infuse the initial dose of cardioplegic solution and the interval to achieve complete electrocardiographic arrest were significantly longer in patients in whom the retrograde route was used (Figs 1, 2). In no patient did electromechanical activity return during the interval between cardioplegia infusions. No patient required intraaortic balloon counterpulsation, and there were no operative deaths. The need for inotropic agents after termination of cardiopulmonary bypass was more frequent in the retrograde group, but the difference was not significant (6 versus 2; p = ). The

686 FIORE ET AL Ann Thorac Surg 1989:47:684-8 -.- Rcsc Fig 2. Coinparisori of the titire to achierie electroiiirchnnical arrest during the initial cardioplegia infusion. Data are showti as the itiean 5 the standard error of the mean. ( = aortic root cardioplegia; RCSC = retrograde coronary sinus cardioplegia.) number of trials required to separate the patient from the extracorporeal circuit ( group, 1. 2.9, and RCSC group, 1.1 *.8; p = ) and the number of electric shocks required to defibrillate the heart ( group, 2.2 *.3, and RCSC group, 1.9 *.4; p = ) were also similar. The frequency of new-onset postoperative atrial fibrillation was slightly greater in patients receiving (31% versus 2%; p = ). No significant differences were noted between the and RCSC groups with respect to the ratio of LDH, and LDH, levels measured on the first and second postoperative days. Four patients had perioperative transmural infarctions as defined by new Q waves on the electrocardiogram and elevated myocardial enzymes ( group, 3, and RCSC group, 1). The curve of the myocardial-specific isoenzyme of creatine kinase demonstrated peak enzyme levels at four hours ( group) and eight hours (RCSC group) after aortic unclamping (Fig 3). Although a trend toward greater enzyme release was noted in those patients receiving retrograde cardioplegia, the difference was not significant. Right ventricular performance was well preserved by Fig 4. Right rientricular stroke ruork Time index (h) (RVSWI) at interrmls after ~ L _ l... l... l ~ ~ ~ l ~ ~ ~ cross-clainp reirrot~nl. Data are shown as the mean 5 the standard error of the rmwn. ( = aortic root cardiople~yia; RCSC = retrop~de coronary siriirs cnrdiojdegia.) either route of cardioplegia delivery (Fig 4). There was a trend toward better left ventricular function in those patients receiving antelograde cardioplegia but the difference reached significance only at 12 hours after aortic unclamping (Fig 5). It was no longer different at 24 hours, when both groups reached baseline levels. Comment Cardioplegia delivery through the aortic root is an established method for safe and effective myocardial preservation during elective revascularization. Cardioplegia administration is simple, diastolic arrest is rapid, and ventricular function after reperfusion is well preserved. In patients with coronary xtery disease, the major disadvantage of this technique is the potential heterogeneous distribution of the carclioplegic solution because of coronary artery stenoses or occlusions. Areas supplied by obstructed coronary arteries can be subject to inadequate cardioplegia delivery, which can cause insufficient cooling of the myocardium and also allow continued electrome- 6 T i r l -.- Rcsc m 7 Y n. 9 1 61 -- RCSC Time (h) Fig 3. Conrparisori of tiyocardial enzyine release: levels of the iii!/ocnrdial-specific isoenzyme of creatirie kiriase (CPK-MB) obtniried froiii uenoiis blood samples before aiid after aortic cross-claiiipirig. Vnta are shown as the inearl 2 the standard error of the iiieari. ( = aortic roof cardioplegia; RCSC = retro<yradr coronar!/ sirzirs cardioplegia.). I... I... I... I - i Time (h) Fig 5. Left zieritricrtlar strokr?iwk index (LVSWI) at intervals after cross-clamp reiiioual. Vnta are sliori~ri as the m an 5 the standard error of the iiieaii. ( = aortic root cardioplegia; RCSC = retroyradc cororiary sinus cardio~~le~yia.)

Ann Thorac Surg 1989;476848 FIORE ET AL 687 chanical activity. These phenomena result in poor myocardial preservation and increased risk of clinically detectable myocardial injury in the perioperative period. In addition, this route of cardioplegia delivery may be less attractive in patients who have some degree of aortic insufficiency in addition to the coronary artery disease. Retrograde coronary sinus perfusion, on the other hand, relies on the nonobstructed coronary venous system for its delivery, and this provides a homogeneous distribution of cardioplegia to the myocardium. In addition, this route of delivery is effective regardless of the competence of the aortic valve. A number of investigators [4-61 have determined experimentally that retrograde perfusion of cardioplegia is safe and possibly a more effective means of myocardial protection than aortic root delivery, particularly in the setting of acute coronary artery occlusion. Despite these experimental results, there is a paucity of comparative clinical data demonstrating superior regional or global myocardial protection with retrograde cardioplegia [7]. This present study directly compares both routes of cardioplegia delivery in a prospective fashion to assess the adequacy of myocardial preservation. The principal advantage of coronary sinus cardioplegia should be better regional myocardial perfusion beyond totally obstructed coronary arteries. Using temperature mapping by thermographic analysis, Shapira and associates [8] found more uniform cooling in inflow-restricted regions of patients undergoing operation for severe and extensive coronary artery disease when retrograde cardioplegia was used. In our series, ventricular septal but not regional temperature was monitored. When combined with topical myocardial cooling, both routes of cardioplegia delivery provided similar reduction in septal temperature. It is important to recognize that in the setting of elective revascularization, patients usually have chronic stable angina patterns. Thus they have coronary collaterals that are sufficiently well developed to ensure homogeneous myocardial cooling independent of the route chosen for cardioplegia infusion. A number of drawbacks have been associated with retrograde perfusion techniques. Overinflation of the balloon catheter or high intracoronary sinus infusion pressure can cause rupture of the coronary sinus. This did not occur in our series. Coronary sinus injury has been reduced with the introduction of the soft, pear-shaped balloon catheter designed by Gundry [9]. The perfusion pressure can be monitored and maintained between 35 and 4 mm Hg, thus avoiding myocardial hemorrhage and edema, which can result from barotrauma during retrograde infusion. Although a pursestring suture in the coronary sinus has been suggested for catheter stabilization, we have not found this advantageous. Several investigators [lo, 111 have advocated the concomitant use of an aortic root vent to permit the coronary artery effluent to escape, thus maintaining a coronary sinus-aortic pressure gradient. We did not routinely find this necessary, as the majority of coronary sinus flow empties into the cardiac chambers through the anterior cardiac veins and the lesser coronary venous system. A major objection to retrograde perfusion has been inadequate right atrial and right ventricular protection. It has been suggested that the right ventricle might be underperfused by the retrograde method because the right ventricular free wall drains directly into the thebesian veins and the right atrium. Experience in this study demonstrates good preservation of right ventricular stroke work index postoperatively, and supports the previous observations of Menasche and associates [12] that coronary sinus perfusion can adequately preserve right atrial and right ventricular function. The need for bicaval cannulation and slow administration of cardioplegic solution have made surgeons reticent to adopt the retrograde method. This study demonstrated that the time to infuse the initial dose of cardioplegia and the time to achieve electromechanical arrest were significantly prolonged when the retrograde route was used. The heart is fibrillating during this prolonged initial infusion interval, and this may cause a reduction in highenergy metabolites and late ventricular dysfunction. This could explain the trend toward improved left ventricular stroke work index in patients receiving anterograde cardioplegia. Buckberg [13] recently suggested that this problem can be circumvented by infusing cardioplegia first through the aortic root to achieve early diastolic arrest and subsequently through the coronary sinus or right atrium to provide more homogeneous distribution. We did not combine these techniques to avoid a potential bias in assessing the advantages of one method over the other. Reasoning that the additional thebesian flow from the right side of the heart may be helpful, some authors [14, 151 have preferred right atrial cardioplegia over coronary sinus infusions. Fabiani and colleagues [ 161 demonstrated superior left ventricular function, lower cardiac isoenzyme levels, and fewer postoperative arrhythmias when the right atrial route was used for delivery instead of the coronary sinus. More recently, Diehl and associates [17] combined aortic root and right atrial cardioplegia delivery in patients undergoing elective myocardial revascularization. They demonstrated better postischemic right ventricular recovery and a slight improvement in left ventricular ejection fraction in patients receiving combined cardioplegia delivery compared with conventional aortic root infusion. The advantages of right atrial cardioplegia delivery appear to be simplicity of technique and contact cooling of all right-sided structures. The presence of a patent foramen ovale or an atrial septal defect precludes the use of this technique. Our study was intentionally limited to the subset of patients with adequate left ventricular function and a stable pattern of angina pectoris. In this select patient population, we have demonstrated that myocardial preservation using the coronary sinus is equivalent to conventional aortic root cardioplegia but offers no advantage. However, the clinical profile of the patient having coronary artery bypass grafting is rapidly changing. Increasing numbers of revascularization procedures are being performed urgently on patients with ongoing myocardial ischemia. It is this subset of patients with an ischemic myocardium who might be better served with the retrograde cardioplegia technique. Patients with unstable angina pectoris, those who require reoperation in

688 FIORE ET AL Ann Thorac Surg 1989:47:68&8 the presence of stenotic bypass grafts, and patients with acute ischemia after failed balloon angioplasty all have lesions that preclude optimal delivery of cardioplegia by the anterograde route. Retrograde cardioplegia may prove to be a more effective technique for myocardial preservation in these emergency situations. We gratefully acknowledge the assistance of Majella Kleffner and Cheryl Bauer in the preparation of the manuscript, and the technical assistance of Mike Stegenga. References 1. 2. 3. 4. 5. 6. Principal Investigators of CASS and Their Associates. The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study. Circulation 1981;63(Suppl 1):1-81. Weisel RD, Lipton IH, Lyall RN, Baird RJ. Cardiac metabolism and performance following cold potassium cardioplegia. Circulation 1978;58(Suppl 1):217-26. Weisel RD, Goldman BS, Lipton IH, et al. Optimal myocardial protection. Surgery 1978;84:812. Mori F, hey TD, Tabayashi K, Thomas R, Misbach GA. Regional myocardial protection by retrograde coronary sinus infusion of cardioplegic solution. Circulation 1986;74(Suppl 3):116-24. Bolling SR, Flaherty JT, Bulkley BH, Gott VL, Gardner TJ. Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion. J Thorac Cardiovasc Surg 1983;86:659-66. Goldstein JP, Salter DR, Abd-Elfattah AS, Murphy CE, Morris JJ 111, Wechsler AS. Protective effect of coronary sinus cardioplegia during two hours of cardiac arrest. Surg Forum 1985;36:195-7. 7. 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 4 patients. Circulation 1986;74(Suppl 3):1515. 8. Shapira N, Lemole GM, Spagna PM, Bonner FJ, Fernandez J, Morse D. Antegrade and retrograde infusion of cardioplegia: assessment by thermovision. Ann Thorac Surg 1987;43:92-7. 9. Gundry SR. Retrograde cardioplegia: myocardial protection via the coronary veins--1986. In: Mohl W, Faxon D, Wolner E (eds). CSI-a new approach to interventional cardiology. New York: Springer-Verlag, 1986:7%5. 1. Gundry SR, Kirsh MM. A comparison of retrograde cardioplegia versus antegrade cardioplegia in the presence of coronary artery obstruction. Ann Thorac Surg 1984;38:1247. 11. Menasche P, Piwnica A. Retrograde cardioplegia through the coronary sinus. Ann Tliorac Surg 1987;44:214-6. 12. Menasche P, Piwnica.4. Retrograde coronary sinus perfusion. In: Roberts AJ, ed. Myocardial protection in cardiac surgery. New York: Marcel Dekker, 198725142. 13. Buckberg GD. Antegrade cardioplegia, retrograde cardioplegia, or both [Editorial]? Ann Thorac Surg 1988;45:589-9. 14. Fabiani JN, Swanson I, Deloche A, Carpentier AF. Right atrial cardioplegia. In: Roberts AJ, ed. Myocardial protection in cardiac surgery. New York: Marcel Dekker, 1987:5514. 15. Bloom MB, Diehl JT, Eichhorn EJ, et al. Clinical comparison of retrograde versus aortic root cardioplegia: effect of right heart intracavitary cool..ng on the incidence of postoperative atrial arrhythmia. Surg Forum 1987;38:258-6. 16. Fabiani J-N, Deloche A, Swanson J, Carpentier A. Retrograde cardioplegia through the right atrium. Ann Thorac Surg 1986;41: 11-2. 17. Diehl JT, Eichhorn El, Konstam MA, et al. Efficacy of retrograde coronary sinus cardioplegia in patients undergoing myocardial revascularization: a prospective randomized trial. Ann Thorac Surg 1988;45:59562.