Total complement inhibition: an effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass.

BACKGROUND: Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. METHODS AND RESULTS: In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67+/-0.17 for unmodified; 2.80+/-0.08 for HB; 3.35+/-0.10 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6+/-0.7% for unmodified; 33.2+/-1.9% for HB; 19.0+/-2.4% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; P<0.05 versus unmodified and HB groups). CONCLUSIONS: Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.

Enhanced preservation of acutely ischemic myocardium and improved clinical outcomes using glucose-insulin-potassium (GIK) solutions.

Although the primary energy source for normal myocardium is free fatty acids, glucose appears to be a more favorable energy substrate for the myocardium during ischemia and reperfusion. Glucose-insulin-potassium (GIK) solutions have been shown to limit ischemic damage in experimental models of ischemia. This review summarizes our experimental and clinical studies involving GIK solutions during urgent surgical revascularization of ischemic myocardium. A pig model was used to simulate the conditions of urgent coronary artery bypass graft (CABG) surgery. The second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion. Animals receiving GIK during the periods of coronary occlusion and reperfusion had significantly less tissue acidosis, better recovery of wall motion scores, and smaller infarct size. In a prospective, randomized, clinical study involving patients undergoing CABG surgery for unstable angina, GIK therapy resulted in higher cardiac indices, less weight gain, earlier extubation, lower incidence of atrial arrhythmia, and shorter ICU and hospital stays. In conclusion, GIK enhances myocardial performance during ischemia and results in faster recovery after CABG surgery for unstable angina.

Importance of topical hypothermia during heterogeneous distribution of cardioplegic solution.

Recent studies have suggested that topical hypothermia may be unnecessary during coronary bypass operations because of possible pulmonary complications resulting from phrenic nerve damage. This study was undertaken to determine whether topical hypothermia is necessary for optimal myocardial protection when distribution of the cardioplegic solution is heterogeneous because of coronary occlusions. Twenty pigs were subjected to 120 minutes of ischemic arrest with multidose potassium crystalloid cardioplegia (4 degrees C). During arrest, the mid-left anterior descending coronary artery was occluded with a snare that was released on reperfusion. Ten of these pigs received topical hypothermia and 10 others served as controls. Hearts protected with topical hypothermia had lower temperatures in the left anterior descending (7.0 degrees +/- 0.7 degree C versus 18.5 degrees +/- 0.5 degree C; p less than 0.05) and circumflex regions (8.9 degrees +/- 0.5 degree C versus 15.5 degrees +/- 0.5 degree C; p less than 0.05). The pH values were higher in hearts protected with topical hypothermia in both the left anterior descending (7.36 +/- 0.09 versus 6.73 degrees +/- 0.07; p less than 0.05) and circumflex regions (7.40 +/- 0.07 versus 7.05 +/- 0.07; p less than 0.05). Topical hypothermia also resulted in better preservation of postischemic stroke work index (0.64 +/- 0.06 versus 0.40 +/- 0.08 gm-m/kg; p less than 0.05) and wall motion scores (1.0 +/- 0.3 hypothermia versus 1.8 +/- 0.4 no hypothermia; p less than 0.05). We conclude that topical hypothermia affords maximal myocardial protection when coronary occlusions are present and should be used during all coronary operations.

Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion.

Recent experimental studies have shown that pressure-controlled intermittent coronary sinus occlusion effectively reduces both infarct size and myocardium at risk after coronary artery occlusion. This study was undertaken to determine whether this modality was equally effective in altering reperfusion damage after a period of ischemic arrest. Fourteen pigs were placed on cardiopulmonary bypass and subjected to 2 hours of ischemic arrest with multidose potassium crystalloid cardioplegia supplemented with topical and systemic hypothermia (28 degrees C). During arrest, the mid-left anterior descending artery was occluded with a snare, which was released immediately after aortic unclamping. In seven pigs, a 7F balloon-tipped catheter was positioned in the coronary sinus and pressure-controlled intermittent coronary sinus occlusion was performed for 60 minutes after aortic unclamping. Seven other pigs served as controls. Parameters measured included stroke work index, ejection fraction, and myocardial pH in the distribution of the distal left anterior descending artery. Pigs treated with pressure-controlled intermittent coronary sinus occlusion had a significantly higher myocardial pH (6.99 +/- 0.06 versus 6.67 +/- 0.05, p less than 0.01), ejection fraction (50% +/- 2% versus 33% +/- 6%, p less than 0.01), and stroke work index (0.87 +/- 0.07 versus 0.61 +/- 0.05 gm-m/kg, p less than 0.01) after 60 minutes of reperfusion compared with those of the group not treated in this way. We conclude that pressure-controlled intermittent coronary sinus occlusion effectively reverses reperfusion damage after periods of ischemic arrest.

Determinants of discharge following coronary artery bypass graft surgery.

The optimal time for discharge following coronary artery bypass graft (CABG) surgery is uncertain and varies among institutions. This study was undertaken to determine what factors may discriminate between early and late discharge following surgery. In 177 consecutive patients undergoing isolated CABG procedures, three groups were formed retrospectively according to the number of days hospitalized post CABG: group 1, less than or equal to 8; group 2, 9 to 11; group 3, greater than or equal to 12. Parameters found to discriminate between group 1 and group 3 (p less than .05; chi square analysis) included female sex, unstable angina, congestive heart failure (CHF), age greater than or equal to 65 years, and the development of major postoperative complications. Angina class, prior myocardial infarction, extent of coronary artery disease, aortic cross-clamp time, number of bypass grafts, ejection fraction less than 40 percent, or "minor" postoperative complications were not different among groups. Patients discharged less than or equal to 8 days following CABG had no increase in return visits or readmissions less than 60 days post CABG. We conclude that while certain patients can be safely discharged less than or equal to 8 days post CABG, patients who are female, greater than or equal to 65 years, have unstable angina, CHF, or a major postoperative complication are likely to be hospitalized longer.

Effects of left ventricular venting and distention during heterogenous distribution of cardioplegic solution.

The effects of left ventricular venting and distention on myocardial protection during heterogenous distribution of cardioplegic solution remain undefined. This study was undertaken to determine if left ventricular venting enhances and distention impairs myocardial cooling and recovery of global and regional left ventricular function. Twenty-one pigs were placed on cardiopulmonary bypass and subjected to 80 minutes of ischemic arrest with the mid-left anterior descending artery occluded. Hearts were protected with multidose potassium (25 mEq/L) crystalloid cardioplegic solution supplemented with topical (4 degrees C) and systemic (28 degrees C) hypothermia. During arrest, the left ventricle was vented in seven pigs, seven pigs were not vented, and seven others had systemic pump blood infused into the left ventricle to maintain an end-diastolic pressure of 15 mm Hg. Parameters measured included left ventricular temperature, stroke work index, compliance (end-diastolic pressure-end-diastolic volume curves) and wall motion scores (two-dimensional echocardiography). Distended hearts had the lowest mean left ventricular temperature beyond the left anterior descending arterial occlusion (10.1 degrees +/- 1.8 degrees C distended [p less than 0.025 from vented and nonvented groups] versus 14.2 degrees +/- 0.7 degrees C vented versus 15.5 degrees +/- 1.2 degrees C nonvented), the highest postischemic stroke work index (0.78 +/- 0.09 gm-m/kg distended versus 0.62 +/- 0.07 gm-m/kg vented versus 0.66 +/- 0.07 gm-m/kg nonvented at end-diastolic pressure = 10 mm Hg), and the best wall motion scores (0.7 +/- 0.04 distended [p less than 0.025 from vented and nonvented groups] versus 5.5 +/- 1.80 vented versus 4.8 +/- 1.20 nonvented). Postischemic end-diastolic pressure-end-diastolic volume curves were unchanged from preischemic values in each group. We conclude that during heterogenous cardioplegic arrest, left ventricular venting offers no additional myocardial protection and may negate the beneficial effects of moderate (end-diastolic pressure = 15 mm Hg) left ventricular distention.

Detrimental effects of interrupting warm blood cardioplegia during coronary revascularization.

Warm blood cardioplegia has emerged as a substitute for cold blood cardioplegia as a method of myocardial protection. However, the continuous infusion of blood in this technique may obscure the operative field and necessitate interruption of warm blood cardioplegia. This experimental study was therefore undertaken to determine whether interrupting warm blood cardioplegia during coronary revascularization would increase myocardial damage. In 30 adult pigs, the second and third diagonal vessels were occluded with snares for 90 minutes. All animals underwent cardiopulmonary bypass and 45 minutes of cardioplegic arrest. During the period of cardioplegic arrest, 10 pigs received intermittent antegrade/retrograde infusion of cold blood cardioplegic solution (4 degrees C) 10 pigs received continuous retrograde infusion of warm blood cardioplegic solution (37 degrees C) at 100 ml/min, and 10 pigs received retrograde infusion of warm blood cardioplegic solution that was interrupted for three 7-minute periods. After aortic unclamping, the coronary snares were released and all hearts were reperfused for 180 minutes. Interrupting retrograde warm blood cardioplegia resulted in more tissue acidosis during cardioplegic arrest (6.20 +/- 0.16 interrupted retrograde warm blood cardioplegia and 6.45 +/- 0.12 continuous retrograde warm blood cardioplegia, both p < 0.05 compared with 6.98 +/- 0.17 intermittent antegrade and retrograde cold blood cardioplegia), decreased echocardiographic wall-motion scores (4 [normal] to -1 [dyskinesis]; 2.06 +/- 0.30 interrupted retrograde warm blood cardioplegia, p < 0.05 compared with 3.30 +/- 0.40 intermittent antegrade and retrograde cold blood cardioplegia, 2.80 +/- 0.40 continuous retrograde warm blood cardioplegia), and increased tissue necrosis as measured by the area of necrosis/area at risk (38% +/- 5% interrupted retrograde warm blood cardioplegia, p < 0.05 compared with 21% +/- 2% intermittent antegrade and retrograde cold blood cardioplegia; 25% +/- 2% continuous retrograde warm blood cardioplegia). We concluded that interrupting warm blood cardioplegia during coronary revascularization diminishes the effectiveness of warm blood cardioplegia and results in increased ischemic damage.

Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting.

OBJECTIVE: This prospective, randomized, clinical study was undertaken to determine whether glucose-insulin-potassium solutions would benefit patients undergoing coronary artery bypass grafting because of unstable angina. METHODS: The study group consisted of 30 patients with unstable angina who required coronary artery bypass grafting. In 15 patients, glucose-insulin-potassium solution (30% dextrose in water; K+, 80 mEq/L: regular insulin, 50 units) was given intravenously at 1 ml/kg per hour after induction of anesthesia and administration continued for 12 hours after aortic unclamping. Fifteen patients in a separate group received 5% dextrose in water intravenously at 50 ml/hr. RESULTS: Patients treated with glucose-insulin-potassium solution had higher cardiac indices (2.8 +/- 0.1 vs 2.0 +/- 1 L/min per square meter; p < 0.001), lower inotrope scores (0.06 +/- 0.01 vs 0.46 +/- 0.19; p = 0.041), and less weight gain (6.4 +/- 9 vs 11.6 +/- 1.1 pounds; p < 0.001) and had shorter times of ventilator support (8.3 +/- 0.6 vs 14.2 +/- 0.2 hours; p = 0.003). They had a significantly lower incidence of atrial fibrillation (13.3% vs 53.3%; p = 0.020) and had shorter stays in the intensive care unit (14.8 +/- 1.3 vs 31.6 +/- 5.2 hours; p = 0.002) and in the hospital (6.0 +/- 0.4 vs 8.0 +/- 0.7 days; p = 0.010). CONCLUSIONS: We conclude that glucose insulin-potassium therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting.

Detrimental effects of premature use of inotropic drugs to discontinue cardiopulmonary bypass.

Ten dogs underwent 45 minutes of normothermic ischemic arrest. After 15 minutes of reoxygenation, none could support the systemic circulation independently. In five dogs, we could discontinue bypass (cardic output 70 to 100 cc/kg/min) by giving dopamine (10 to 30 mcg/kg/min). In five other dogs, total cardiopulmonary bypass was prolonged for an additional 30 minutes and no dopamine was given. During control and at 15 and 45 minutes after aortic unclamping, we measured myocardial blood flow (microspheres), metabolism (oxygen uptake and lactate), water content (wet/dry weight), left ventricular compliance (intraventricular balloon), and performance (isovolumetric and Starling function curves). Dogs treated with prolonged bypass showed progressive improvement in ventricular compliance, function, and water content and did not require inotropic drugs when bypass was discontinued 45 minutes after ischemia. In contrast, dogs receiving dopamine exhibited more myocardial edema (3.3% versus 1.7% water gain), worse ventricular compliance (18% versus 55% recovered at 25 ml left ventricular volume), poorer contractility (58% versus 70% recovery of +dP/dt), generated 50% less stroke work at a left atrial pressure of 25 mm Hg (0.25 versus 0.52 gm/kg), failed to augment oxygen uptake to meet the metabolic demands of the working heart (11% versus 45% increase in oxygen uptake), and required continued inotropic support to discontinue extracorporeal circulation. We conclude that (1) limited prolongation of total bypass enhances recovery from ischemic damage and (2) use of inotropic drugs to prematurely discontinue extracorporeal circulation will impede recovery by accentuating myocardial edema and further decreasing ventricular compliance, performance, and oxygen utilization.

Effects of coronary revascularization on regional wall motion. An intraoperative two-dimensional echocardiographic study.

Although coronary artery bypass grafting effectively reduces the symptoms of myocardial ischemia, its immediate effect on regional wall motion dysfunction is not well defined. This intraoperative study was undertaken to determine whether bypass grafting improves regional wall motion in areas of preoperative ischemic dysfunction. In 17 patients undergoing coronary bypass, short-axis echocardiograms were obtained with the chest open 30 minutes before and after cardiopulmonary bypass. Regional wall motion was calculated quantitatively as the percent increase in segmental wall thickness during systole, with 40% thickening or less defined as indicating ischemic dysfunction. Qualitatively, it was evaluated by visual changes in endocardial wall motion according to a graded score (0 = normal to 4 = dyskinesia). Of the 136 segments studied, 44 (32%) had evidence of ischemic dysfunction before coronary bypass. When regional wall motion was analyzed in all 136 segments after coronary bypass, there was no significant change in either quantitative indices (62% +/- 7% before grafting versus 58% +/- 6% after grafting) or qualitative indices (0.19 +/- 0.06 versus 0.17 +/- 0.06). However, in those segments with ischemic dysfunction before grafting, there was a significant increase in quantitative indices of regional wall motion after grafting (24% +/- 2% versus 50% +/- 5%; p less than 0.02). By contrast, qualitative indices continued to show no significant improvement (1.3 +/- 0.1 versus 1.05 +/- 0.2). We conclude that coronary artery bypass grafting significantly improves areas of ischemic regional wall dysfunction. These changes can be difficult to detect with visual qualitative methods and are best analyzed by techniques assessing changes in segmental wall thickness.

Warm versus cold blood cardioplegia--is there a difference?

This experimental study sought to compare the effectiveness of warm blood cardioplegia versus cold blood cardioplegia in protecting areas of ischemic myocardium during urgent coronary revascularization. In 40 adult pigs, the second and third diagonal vessels were occluded with snares for 90 minutes. All animals were then placed on cardiopulmonary bypass and underwent 45 minutes of cardioplegic arrest followed by 3 hours of reperfusion during which time the coronary snares were released. During the period of cardioplegic arrest, 10 pigs received antegrade continuous warm blood cardioplegic solution (37 degrees C) at 100 ml/min; 10 animals received retrograde warm blood cardioplegic solution at 100 ml/min; 10 received intermittent, antegrade cold blood cardioplegic solution (4 degrees C), and 10 animals received intermittent, antegrade/retrograde cold blood cardioplegic solution. Hearts protected with antegrade warm blood cardioplegic solution had the lowest pH values in the area at risk (6.59 +/- 0.10 antegrade warm blood cardioplegia versus 6.80 +/- 0.10 retrograde warm blood cardioplegia versus 6.72 +/- 0.18 antegrade cold blood cardioplegia versus 6.85 +/- 0.15 antegrade/retrograde cold blood cardioplegia and the highest area of necrosis (42% +/- 3% antegrade warm blood cardioplegia versus 26% +/- 2% [p < 0.05 from antegrade warm blood cardioplegia] retrograde warm blood cardioplegia versus 31% +/- 2% [p < 0.05 from antegrade warm blood cardioplegia] antegrade cold blood cardioplegia versus 21% +/- 2% [p < 0.05 from antegrade warm blood cardioplegia] antegrade/retrograde cold blood cardioplegia). We conclude that in the presence of an acute coronary occlusion with ischemic myocardium, warm blood cardioplegic solution should be given in a continuous retrograde fashion and does not result in myocardial protection superior to the protection that can be achieved with antegrade/retrograde cold blood cardioplegic solution.

Reversal of ischemic damage with secondary blood cardioplegia.

After severe ischemic injury, it is usually necessary to prolong bypass to enhance recovery. This study tests the hypothesis that the best reversal of ischemic damage is achieved by briefly rearresting the postischemic heart with a continuous infusion of an oxygenated cardioplegic solution (secondary blood cardioplegia) during the period when bypass must be prolonged. Twenty dogs underwent 45 minutes of normothermic ischemic arrest. Fifteen minutes after unclamping, no heart could support the systemic circulation. In all dogs, oxygen demands were lowered by extending bypass for 30 minutes. In 10 of these dogs, demands were further lowered by rearresting the heart for 5 minutes with a continuous infusion of a 37 degrees C blood cardioplegic solution (K+28 mEq/L; pH 7.6; Ca++ 1 mEq/L) at a pressure of 50 mm Hg. Hearts treated with secondary blood cardioplegia showed greater recovery in the rate of contraction (-dP/dt 75% versus 62%, p less than 0.05) and relaxation (-dP/dt 76% versus 58%, p less than 0.05), better recovery of compliance (85% versus 51%, p less than 0.05), a higher stroke work index (0.72 versus 0.50 gm-m/Kg, p less than 0.05), and more ability to augment oxygen uptake (85% versus 45%, p less than 0.05) to meet the demands of the working heart than hearts treated by prolonging bypass alone. We conclude that rearresting the heart with a brief, continuous infusion of a blood cardioplegic solution results in more complete reversal of ischemic damage than possible by prolongation of a bypass alone. We believe that the increased recovery with secondary cardioplegia results from diversion of delivered oxygen toward reparative processes rather than its being expended needlessly on electromechanical work during the time when bypass must be prolonged.

Early discharge after coronary artery bypass graft surgery: are patients really going home earlier?

OBJECTIVE: This study was undertaken to determine whether early discharge after coronary artery bypass grafting allows patients to return home earlier or merely increases the use of outpatient nursing and inpatient rehabilitation services. METHODS: Patterns of discharge were analyzed in 407 patients undergoing bypass grafting in 1990, when there were no early extubations or fast track protocols, and compared with 379 patients in 1998, when these protocols were used. RESULTS: Patients in 1998 had a higher prevalence of class IV angina (35.3% vs 22.8%; P =.006), urgent/emergency surgery (58.3% vs 44.9%; P =.015), and lower ejection fractions (48.9% +/- 16.4% vs 52.9% +/- 13.5%; P =.0002). Despite these increased risk factors, 1998 patients spent less time receiving ventilatory support (10.2 +/- 9.2 vs 26.7 +/- 15.7 hours; P <.001) and had a shorter length of stay (5.4 +/- 2.5 vs 9.2 +/- 4.3 days; P <.001). However, fewer 1998 patients were discharged home (56.7% vs 97.0%; P <.0001). A higher percentage of 1998 patients (43.3% vs 2.9%; P <.00001) were discharged to extended care facilities where their average length of stay was 10.6 +/- 15.1 days. Readmission to the Boston Medical Center was also more common in 1998 patients (5.3% vs 0.5%; P <.0001). CONCLUSIONS: Early extubation and fast track protocols have resulted in earlier discharge from acute care facilities. However, the anticipated earlier return to home has been offset by the increased use of outpatient nursing services, discharges to extended care facilities, and hospital readmissions.

Intraoperative angioscopy of saphenous vein and coronary arteries.

During coronary artery bypass graft operations, the saphenous vein graft and native coronary arteries in 17 patients were examined with a 1.7 mm fiberoptic catheter to determine the feasibility of the procedure and its potential for clinical application. Good to excellent visualization in 10 of 11 proximal and 10 of 10 distal coronary anastomoses was obtained promptly and consistently. Good visualization of native coronary arteries was obtained in only six of 11 vessels. Three of three coronary arteries were visualized through the completed distal anastomosis, whereas only three of eight vessels could be visualized directly through the arteriotomy site before completion of the distal anastomosis. The image quality improved with operator experience. Vessel distention by cold crystalloid solution during catheter visualization was also important for obtaining better images. Limitations of the current "state of the art" fiberoptic catheters include the large size relative to the usual dimensions of the native coronary vessels, a lack of perfusion channel, and the absence of an angulation or guiding system. Potentially, angioscopic catheters may be useful as an instructional aid during bypass operations or as a diagnostic tool in monitoring arterial status after thrombolytic intervention, balloon angioplasty, or laser therapy.

Reversal of ischemic damage with amino acid substrate enhancement during reperfusion.

Twenty dogs underwent 15 minutes of normothermic ischemic arrest and 30 minutes of reperfusion while on cardiopulmonary bypass. In 10 control dogs, the reperfusate blood was not modified. In 10 other dogs, the aorta was reclamped and the heart reperfused for 5 minutes with blood containing L-glutamate (0.026M). We measured coronary blood flow (microspheres), left ventricular (LV) metabolism [O2 content, adenosine triphosphate (ATP)], LV compliance (intraventricular balloon), and LV performance (balloon and Starling curves) before and 30 minutes after ischemia. Fifteen minutes of ischemic arrest produced significant depression in contractility and oxidative metabolism. L-Glutamate infusion resulted in higher oxygen uptakes (9.7 versus 6.9 cc/100 gm/min) and allowed more complete recovery of ATP content (80% versus 67%). Glutamate-treated hearts had more complete recovery in the rate of contraction, +dP/dt, (96% versus 68%), and relaxation, --dP/dt (99% versus 72%), the best recovery of compliance (74% versus 88%), and complete (100%) recovery of stroke work index (1.55% versus 0.87% gm - m/kg). We conclude that the addition of L-glutamate to reperfusate blood reverses ischemic damage. We suspect that l-glutamate acts by replenishing Krebs' cycle intermediates lost during ischemia, thereby stimulating oxidative metabolism and enhancing ATP production.

Superiority of substrate enhancement over oxygen free-radical scavengers during extended periods of cold storage for cardiac transplantation.

When cold storage techniques used in cardiac transplantation are extended beyond 3 hours, there is significant depression in ventricular function. This study was undertaken to determine whether the addition of the amino acid L-glutamate or the oxygen free-radical scavengers superoxide dismutase (SOD) and catalase (CAT) during extended periods of cold storage would improve ventricular function. Fifteen rabbit hearts were placed on a Langendorff apparatus, arrested with crystalloid potassium cardioplegia, stored in iced saline solution (3 degrees C) for 5 hours, and then reperfused at 37 degrees C for 1 hour. In five hearts L-glutamate (4 mmol/L) was added to the cardioplegic and reperfusate solutions, and five hearts received SOD (1500 units/kg/L) and CAT (3500 units/kg/L), whereas in five others the cardioplegic and reperfusate solutions were unmodified. Hearts treated with L-glutamate had the best recovery of positive dP/dt (79%* glutamate vs 49%* SOD and CAT vs 36% unmodified), negative dP/dt (76%* glutamate vs 53% SOD and CAT vs 45% unmodified), developed pressure (67%* glutamate vs 51% SOD and CAT vs 45% unmodified), and coronary flow (81%* glutamate vs 79%* SOD and CAT vs 62% unmodified). We conclude that substrate enhancement with L-glutamate provides superior myocardial protection than is possible with the oxygen free-radical scavengers SOD and CAT during extended periods of cold storage for cardiac transplantation.

Effect of cardiopulmonary bypass and global ischemia on human and canine left ventricular mass: evidence for interspecies differences.

Previous studies in dogs suggest that global ischemia with cardiopulmonary bypass causes increased left ventricular (LV) mass and water content. To investigate effects in humans, we developed a simplified method for mass determination by intraoperative two-dimensional echocardiography. LV mass was measured as echocardiographic short-axis myocardial area. This was validated by linear regression versus postmortem LV mass in 10 dogs (r = 0.89) and versus single-plane angiography in 18 patients (r = 0.73). According to this method, there was no change in LV mass (209 gm versus 208 gm; NS) at constant preload in 20 patients during routine operations (eight coronary revascularizations, 10 aortic valve replacements, and two mitral valve replacements). The same method used in 10 dogs after 2 hours of bypass, 60 minutes of normothermic global ischemia, and reperfusion revealed an LV mass increase from 113 +/- 13 gm (SE) to 150 +/- 16 gm (p less than 0.01) at matched preload. In addition, in 14 dogs after 2 hours of bypass alone, LV mass was unchanged (98 +/- 5 gm versus 101 +/- 5 gm; NS) at matched preload. Data recently derived from a separate study in our laboratory revealed a statistically significant increase in canine LV mass when conditions of human cardiopulmonary bypass and cardioplegic arrest were reproduced. We conclude that uncomplicated cardiac operations in humans do not alter LV mass. This supports the safety of crystalloid cardioplegia in humans. While present evidence is not conclusive, it appears that the threshold for edema formation after ischemic injury may be higher in humans than it is in dogs. The clinical relevance of studies of cardioplegia in edematous dog hearts thus deserves careful scrutiny.

Coronary sinus interventions during cardiac surgery.

There is renewed interest in protecting jeopardized myocardium during regional and global ischemia by coronary sinus retroperfusion. Advances in catheter design and imaging techniques have made access to the coronary sinus easier and safer. Retrograde coronary sinus perfusion, aortovenous bypass, pressure-controlled intermittent coronary sinus occlusion, and synchronized retrograde perfusion have emerged as new techniques by which blood can be redirected through the coronary sinus to nourish ischemic myocardium beyond a coronary occlusion. The purpose of this review is to summarize the current results and applications of these coronary sinus interventions, and show how they can benefit the cardiac surgeon in clinical practice.

Determinants of myocardial infarction following emergency coronary artery bypass for failed percutaneous coronary angioplasty.

Acute myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA) often necessitates emergency coronary artery bypass grafting (CABG) and can result in myocardial infarction (MI). This study was undertaken to determine what factors might predispose to MI following emergency CABG for failed PTCA. Since 1980, 24 patients at Boston University Medical Center have undergone emergency CABG following failed PTCA. In 15 patients (63%), there was postoperative evidence of an MI shown by either ECG or enzyme criteria. Variables that predisposed to a perioperative MI (p less than 0.05) included multivessel PTCA, the presence of multiple vessels with 50% stenosis or more, multivessel CABG, and the presence of new ECG changes immediately following failed PTCA. Variables that did not discriminate between the two groups included age, sex, the specific vessel involved during PTCA, or a previous history of MI. The presence of coronary collaterals did not decrease the incidence of MI. This study suggests that patients with multiple major coronary stenoses in whom acute ECG changes develop following failed PTCA are more likely to sustain a perioperative MI following emergency CABG.

Intraoperative echocardiography.

Intraoperative echocardiography has emerged as a new technique by which the cardiac surgeon can more precisely define the operative anatomy and physiology, immediately evaluate the results, and more accurately monitor left ventricular function in the operating room. This review summarizes the current applications of intraoperative two-dimensional and Doppler echocardiography in both the epicardial and transesophageal forms, and discusses the advantages and possible limitations of these methods in the practice of clinical cardiac surgery.