Retrograde coronary sinus perfusion prevents infarct extension during intraoperative global ischemic arrest

To determine whether continuous infusion of cardioplegia retrograde through the coronary sinus could improve the salvage of infarcting myocardium, 54 pigs were utilized in a region at risk model. All hearts underwent 30 minutes of reversible coronary artery occlusion, and were divided into six groups. Group 1 served as controls and underwent two hours of coronary reflow without global ischemic arrest. The remaining five groups were subjected to 45 minutes of cardioplegia-induced hypothermic arrest followed by two hours of normothermic reflow. Group 2 had a single infusion of crystalloid cardioplegia, and Group 3 received an oxygenated perfluorocarbon cardioplegic solution initially and again after 20 minutes of ischemia. After initial cardiac arrest with crystalloid cardioplegia, all hearts in Groups 4, 5, and 6 underwent a continuous infusion of a cardioplegic solution retrograde through the coronary sinus. Group 4 received a nonoxygenated crystalloid cardioplegic solution, Group 5 received an oxygenated crystalloid cardioplegic solution, and Group 6 received an oxygenated perfluorocarbon cardioplegic solution. With results expressed as the percent of infarcted myocardium within the region at risk, Group 2 hearts, which received only antegrade cardioplegia, had a mean infarct size of 44.8 +/- 6.3%, a 2.2-fold increase over controls (p less than 0.05). While antegrade delivery of oxygenated perfluorocarbon cardioplegia (Group 3) and coronary sinus perfusion with nonoxygenated crystalloid cardioplegia (Group 4) limited infarct size to 33.6 +/- 4.7% and 35.3 +/- 5.4%, respectively, only oxygenated cardioplegia delivered retrograde through the coronary sinus (Groups 5 and 6) completely prevented infarct extension during global ischemic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis

Multidose administration of cardioplegic solution during cardiac operation is intended to maintain both electromechanical arrest of the heart and myocardial hypothermia as well as to remove accumulated metabolites of anaerobic glycolysis. This study was conducted to assess the effect of multidose infusion of three different types of cardioplegic solution on tissue acidosis during global myocardial ischemia. Three groups of five dogs each were placed on cardiopulmonary bypass and the aorta was cross-clamped for 3 hours. The hearts were maintained at a constant temperature (20 degrees C) and cardioplegic solution was infused at an initial dose of 500 ml and five supplementary doses of 250 ml administered every 30 minutes. Group 1 received a crystalloid solution weakly buffered with sodium bicarbonate, Group 2 received a blood-based solution, and Group 3 received a crystalloid solution strongly buffered with histidine (Bretschneider's solution). The buffering capacities of the solutions used in Groups 2 and 3 were 40 and 60 times, respectively, that of the solution used in Group 1. The average myocardial tissue pH at the end of 3 hours of ischemia was 6.54 +/- 0.07 in Group 1, 7.23 +/- 0.05 in Group 2, and 7.19 +/- 0.06 in Group 3 (Group 1 significantly lower than Groups 2 and 3). Multidose infusion of a cardioplegic solution with low buffering capacity was unable to prevent the progressive development of tissue acidosis during 3 hours of ischemia. However, the multidose infusion of either blood-based or crystalloid solutions with high buffering capacity completely prevented any further reduction of tissue pH after the first 30 minutes of ischemia.     

Reduction in myocardial acidosis using blood cardioplegia

The composition of the ideal cardioplegic solution is controversial. Blood cardioplegia is an attractive alternative to standard crystalloid solutions, though its superiority in preserving myocardial metabolism has not been demonstrated. Using a new pH electrode system, this study contrasts the effects of blood and crystalloid solutions upon the generation of myocardial acidosis during global ischemia. Thirty-eight mongrel dogs underwent a 120-min period of aortic cross clamping using systemic hypothermia. To maintain myocardial temperature below 15 degrees C, 19 dogs received multiple doses of a bicarbonate containing crystalloid cardioplegic solution (Group I), while 19 dogs received multiple doses of blood cardioplegia (Group II). Myocardial pH and temperature were continuously monitored in the subendocardial region of the left ventricle. There was no difference in baseline pH between Group I (7.13 +/- 0.05) and Group II (7.17 +/- 0.05, P:NS). With systemic cooling and the initial bolus of cardioplegia, myocardial pH rose to 7.42 +/- 0.04 in Group I and 7.42 +/- 0.06 in Group II (P:NS). After 120 min of global ischemia, myocardial pH decreased to 6.61 +/- 0.05 in Group I and 7.07 +/- 0.05 in Group II (P less than 0.001). Blood cardioplegia was most effective during the first hour of aortic cross clamp when myocardial pH rose by 0.13 +/- 0.04 pH units. In contrast, myocardial pH in Group I during the first hour of global ischemia fell -0.35 +/- 0.08 pH units (P less than 0.001 compared to Group II). During the second hour of cross clamp, myocardial pH declined both in Group I (0.26 +/- 0.03 pH units) and in Group II (0.24 +/- 0.05 pH units, P:NS). However, the accumulation of hydrogen ion during the second hour was significantly greater in Group I (+128.0 +/- 21.4 nm/liter) than in Group II (+36.6 +/- 9.0 nm/liter, P less than 0.001). Thus, myocardial acidosis was reduced during the administration of blood cardioplegia when compared to a bicarbonate-buffered crystalloid solution. The salutary effects of blood cardioplegia on myocardial metabolism stem from blood's significant buffering capacity and its ability to deliver oxygen.     

Oxygenation of cardioplegic solutions. Potential for the calcium paradox

Oxygenation of crystalloid cardioplegic solutions is beneficial, yet bicarbonate-containing solutions equilibrated with 100% oxygen become highly alkaline as carbon dioxide is released. In the isolated perfused rat heart fitted with an intraventricular balloon, we recently observed a sustained contraction related to infusion of cardioplegic solution. In the same model, to record these contractions, we studied myocardial preservation by multidose bicarbonate-containing cardioplegic solutions in which first the calcium content and then the pH was varied. An acalcemic cardioplegic solution (Group 1) and the same solution with calcium provided by adding calcium chloride (Group 2) or blood (Group 3) were equilibrated with 100% oxygen. Ionized calcium concentrations were 0, 0.10 +/- 0.06, and 0.11 +/- 0.07 mmol/L and pH values were 8.74 +/- 0.07, 8.54 +/- 0.08, and 8.40 +/- 0.07, all highly alkaline. Hearts were arrested for 2 hours at 8 degrees +/- 2.5 degrees C and reperfused for 1 hour at 37 degrees C. At end-arrest, myocardial adenosine triphosphate was depleted in all three groups, significantly in Groups 2 and 3. In Group 1 the calcium paradox developed upon reperfusion, with contracture (left ventricular end-diastolic pressure = 60 +/- 7 mm Hg), creatine kinase release up to 620 +/- 134 U/L, a profound further decrease in adenosine triphosphate to 1.9 +/- 1.7 nmol/mg dry weight, and either greatly impaired or no functional recovery (17% +/- 10% of prearrest developed pressure). Three hearts in this group released creatine kinase during arrest and did not resume beating during reperfusion. In Groups 2 and 3, the calcium paradox did not occur; functional recovery was 61% +/- 4% and 71% +/- 9% at 5 minutes of reperfusion. In two additional groups (4 and 5), the pH of the acalcemic cardioplegic solution was decreased by equilibration with 2% and 5% carbon dioxide in oxygen to 7.53 +/- 0.03 and 7.11 +/- 0.02. Contractions during arrest were smaller than in Groups 1, 2, and 3; adenosine triphosphate was maintained during arrest; functional recovery was 101% +/- 3% and 96% +/- 4% at 5 minutes of reperfusion. We conclude that acalcemic solutions with carbon dioxide are superior to highly alkaline calcium-containing solutions. If oxygenation of cardioplegic solutions, of proved value, causes severe alkalinity, then calcium paradox may result even with hypothermia. This hazard is prevented by adding calcium or blood to the solution or carbon dioxide to the oxygen used for equilibration.     

Comparison of alternative cardioplegic techniques

Cold potassium cardioplegia provides adequate protection for coronary bypass operations, but severe coronary stenoses limit cardioplegic delivery to ischemic regions. The traditional technique delivers cardioplegic solution into the aortic root during the performance of distal anastomoses. The proposed alternative technique constructs proximal as well as distal anastomoses during a prolonged cross-clamp period, but permits more uniform cooling. The two techniques were compared in a prospective concurrent trial of 45 patients undergoing elective coronary bypass grafting. The traditional technique was employed in 26 patients (Group A) and the alternative technique in 19 patients (Group B). In both groups, 700 to 1,000 ml of a crystalloid cardioplegic solution was infused into the aortic root after application of the aortic cross-clamp. In Group A (traditional technique), 500 ml was infused into the aortic root after each distal anastomosis. In Group B (alternative technique), cardioplegic solution was administered through the vein graft after each distal anastomosis, and a proximal anastomosis was constructed after distal anastomoses to the most ischemic regions to permit continued cardioplegic delivery to these regions. The cross-clamp period was shorter in Group A than in Group B (44 +/- 15 versus 60 +/- 18 minutes, p less than 0.01), but the mean temperature in the most ischemic region was warmer (Group A, 19 degrees +/- 3 degrees C; Group B, 15 degrees +/- 3 degrees C, p less than 0.05). The postoperative CK-MB was higher in Group A (Group A, 47 +/- 36; Group B, 21 +/- 9 IU/L, p less than 0.01). Cardiac lactate production persisted longer in Group A (Group A, 4 +/- 1; Group B, 1 +/- 1 hours postoperatively, p less than 0.05). Volume loading 4 hours postoperatively produced a similar increase in left atrial pressure and cardiac index in both groups. In response to volume loading, Group A patients produced lactate, but Group B patients extracted lactate (change in cardiac lactate extraction: Group A, -1.7 +/- 2.3; Group B, +2.5 +/- 5.1 mg/dl, p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cooling and immediate reperfusion. This alternative technique resulted in less injury (CK-MB release) and more rapid recovery of myocardial metabolism.     

Myocardial protection during prolonged aortic cross-clamping. Comparison of blood and crystalloid cardioplegia

We compared the ability of blood and crystalloid cardioplegia to protect the myocardium during prolonged arrest. Twelve dogs underwent 180 minutes of continuous arrest. Group I (six dogs) received 750 ml of blood cardioplegic solution (potassium chloride 30 mEq/L) initially and every 30 minutes. Group II (six dogs) received an identical amount of crystalloid cardioplegic solution (potassium chloride 30 mEq, methylprednisolone 1 gm, and 50% dextrose in water 16 ml/L of electrolyte solution). Temperature was 10 degrees C and pH 8.0 in both groups. Studies of myocardial biochemistry, physiology, and ultrastructure were completed before arrest and 30 minutes after normothermic reperfusion. Biopsy specimens for determination of adenosine triphosphate were obtained before, during, and after the arrest interval. Regional myocardial blood flow, total coronary blood flow, and myocardial oxygen consumption were statistically unchanged in Group I (p greater than 0.05). Total coronary blood flow rose 196% +/- 49% in Group II (p less than 0.005), and left ventricular endocardial/epicardial flow ratio fell significantly in this group from 1.51 +/- 0.18 to 0.8 +/- 0.09, p less than 0.01 (mean +/- standard error of the mean. The rise in myocardial oxygen consumption was not significant in this group (34% +/- 36%, p greater than 0.05). Ventricular function and compliance were statistically unchanged in both groups. In Group II, adenosine triphosphate fell 18% +/- 3.4% (p less than 0.005) after 30 minutes of reperfusion; it was unchanged in Group I. Ultrastructural appearance in both groups correlated with these changes. We conclude that blood cardioplegia offers several distinct advantages over crystalloid cardioplegia during prolonged arrest.     

Structural and metabolic correlates of cell injury in the hypertrophied myocardium during valve replacement

To characterize the ultrastructural and metabolic changes occurring in the hypertrophied ventricle during cardiac operations in man, we studied 36 patients with valvular heart disease undergoing valve replacement, during which multiple doses of cold potassium cardioplegic solution were administered (Group I). Each patient had substantial ventricular hypertrophy according to measurements made of left ventricular mass, with a mean of 232.1 +/- 19.8 gm/m2 (normal: 92 +/- 16 gm/m2). Serial biopsy specimens were obtained from the left ventricular apex at the initiation of bypass, during the cross-clamp interval, and during reperfusion. Each specimen was scored from 0 to 4 according to ischemic changes in nuclear chromatin, mitochondrial swelling, myofibrillar edema, glycogen depletion, and overall cell morphology. Myocardial pH and temperature were measured continuously in the left ventricular free wall. During the cross-clamp period, ischemic injury was evidenced by changes in nuclear chromatin (0.38 +/- 0.10 to 1.25 +/- 0.21, p less than 0.0001), intracellular edema (0.43 +/- 0.06 to 0.97 +/- 0.14, p less than 0.002), overall cell morphology (0.37 +/- 0.06 to 0.97 +/- 0.14, p less than 0.001), and mitochondria (0.10 +/- 0.05 to 0.19 +/- 0.07, p less than 0.0001). During reperfusion, mitochondrial swelling increased further (0.19 +/- 0.07 to 0.35 +/- 0.08, p less than 0.0001) and glycogen stores were depleted (0.63 +/- 0.13 to 0.96 +/- 0.17, p less than 0.02), while the other structures remained unchanged. Myocardial pH declined during ischemic arrest from 6.89 +/- 0.04 to 6.40 +/- 0.04 (p less than 0.001). The changes in myocardial pH in Group I were compared to changes in myocardial pH in 10 patients (Group II) with no left ventricular hypertrophy undergoing isolated coronary bypass graft operations with the same protective techniques. In contrast to Group I, myocardial pH did not fall in Group II during ischemic arrest (6.98 +/- 0.06 to 6.94 +/- 0.05, p = not significant). Thus, with the use of current myocardial protective techniques, ultrastructural and metabolic changes indicative of ischemia are produced in the hypertrophied myocardium. The structural alterations consist of changes in nuclear chromatin and intracellular edema during the ischemic phase and by mitochondrial swelling during reperfusion.     

Does hypothermic fibrillatory arrest improve myocardial protection during emergency revascularization?

Hypothermic fibrillatory arrest (HFA) was compared with conventional hypothermic cardioplegic arrest (HCA) in a model of acute regional ischemia. In 20 pigs, the left anterior descending coronary artery was occluded for 30 minutes before cardiopulmonary bypass. In the HCA group (n = 10), the heart was arrested with a hyperkalemic cold crystalloid solution, whereas in HFA animals (n = 10), the heart was vented and allowed to fibrillate spontaneously without cross-clamping. Miniature pH probes monitored intramyocardial pH during 45 minutes of arrest (HCA or HFA, both with systemic and topical myocardial cooling) and during two hours of coronary reperfusion. Hypothermic fibrillatory arrest did not ameliorate the acidosis in the ischemic (left anterior descending) region; indeed, after two hours of coronary reperfusion, there was a trend toward more acidosis in the postischemic left anterior descending territory in the HFA group. However, HFA did prevent acidosis in the nonischemic (left circumflex) territory. Infarct size expressed as percent of region at risk was 18.1% +/- 3.2% (mean +/- standard error of the mean) in the HCA animals and 18.8% +/- 4.4% in the HFA animals. These results demonstrate that HFA offers no advantage over HCA in protection of regionally ischemic myocardium in a model with minimal collateral circulation.     

Cold cardioplegia versus hypothermia for myocardial protection. Randomized clinical study.

Seventeen of 34 consecutive patients undergoing coronary artery bypass grafting were randomly assigned to one of two methods of myocardial preservation. With the cold cardioplegic method (Group A), a 4 degrees C. asanguineous solution with 30 mEq. of potassium per liter was infused into the aortic root for about 2 minutes immediately after aortic cross-clamping and again after about 45 minutes or when myocardial temperature rose above 19 degrees C. External cardiac cooling was provided by constant infusion of 4 degrees C. Ringer's solution into the pericardium. Seventeen patients were assigned to simple cardiac cooling by hypothermic systemic perfusion before aortic cross-clamping plus external cardiac cooling (Group B). Electromechanical activity ceased within 1 to 2 minutes in Group A but continued throughout the ischemic period in 14 patients in Group B. Myocardial temperature (mean for all observations) during aortic cross-clamping was 17.2 +/- 0.44 degrees C. In Group A and 24.0 +/- 0.70 degrees C. in Group B. Operating conditions were better in Group A. Card-ac function early postoperatively was good in both groups clinically and according to measurements, but only in the cold cardioplegic group (A) was cardiac index not adversely affected by longer cross-clamp time. Myocardial necrosis occurred in both groups but was probably less in the cold cardioplegic group. Thirteen patients (76 percent) in Group A had no electrocardiographic evidence of myocardial injury, compared with eight (47 percent) in Group B (p = 0.08). Eleven (65 percent of Group A had no or short-lived appearance of ceatine phosphokinase isoenzyme (CK-MB), compared with six (35 percent) of Group B (p = 0.08). Time-related CK-MB and SGOT mean levels were consistently lower in Group A.     

Improved distribution of cardioplegia with pressure-controlled intermittent coronary sinus occlusion

Coronary occlusions may alter the distribution of antegrade cardioplegia and result in ischemic damage. This study was undertaken to determine whether pressure-controlled intermittent coronary sinus occlusion (PICSO) could improve antegrade cardioplegic delivery when coronary occlusions are present. Twenty pigs were subjected to 120 minutes of ischemic arrest with antegrade, multidose, potassium crystalloid cardioplegia. During arrest, the mid-left anterior descending artery was occluded with a snare, which was released on reperfusion. In 10 pigs, a balloon-tipped catheter was placed in the coronary sinus and PICSO was performed during each cardioplegia dose. PICSO-treated hearts had faster arrests (27 +/- 5 versus 102 +/- 21 [SE] seconds; p less than 0.02), as well as lower temperatures (18.4 +/- 1.0 versus 22.0 +/- 1.4 degrees C; p less than 0.05) and higher tissue pH (6.58 +/- 0.09 versus 6.31 +/- 0.09; p less than 0.05) just before aortic unclamping. Postischemic end-diastolic volume was unchanged with PICSO, but it decreased in non-PICSO-treated hearts. PICSO-treated hearts generated a higher postischemic stroke work index (0.70 +/- 0.08 versus 0.38 +/- 0.08 g-m/kg; end-diastolic volume, 60 ml; p less than 0.05). We conclude that PICSO improves cardioplegic distribution, thus reducing ischemic injury.     

Influence of the pH of cardioplegic solutions on intracellular pH, high-energy phosphates, and postarrest performance. Protective effects of acidotic, glutamate-containing cardioplegic perfusates

The common practice of using alkalotic cardioplegic solutions is not supported by experimental evidence. The present study was conducted to assess the effects of varying the pH (7.00, 7.40, and 7.70 at 20 degrees C) of a glutamate-containing cardioplegic solution on intracellular pH, high-energy phosphate content, and postarrest functional recovery and to compare the effects of various buffers (glutamate, bicarbonate, TRIS, and histidine) at a given pH (7.00 and 7.40). Isolated perfused rat hearts were subjected to 2 hours of cardioplegic arrest at 15 degrees C followed by 30 minutes of reperfusion. Intracellular pH and high-energy phosphate content were measured at 4 minute intervals by phosphorus 31 nuclear magnetic resonance spectroscopy. These data were correlated with postischemic recovery of function. There was no significant difference between the intracellular pH values recorded at the end of arrest in the three glutamate-containing groups. However, the acidotic solution (pH 7.00) resulted in better preservation than the alkalotic solution (pH 7.70), as evidenced by a higher creatine phosphate content at the end of arrest (61% +/- 9% of control values versus 30% +/- 9% [mean +/- standard error of the mean], p less than 0.05), a higher adenosine triphosphate content at the end of reperfusion (102% +/- 5% versus 82% +/- 6%, p less than 0.05), and a faster recovery of aortic flow (at 3 minutes of reperfusion, 91% +/- 11% versus 51% +/- 11%, p less than 0.05). Subsequent comparison of buffers showed that bicarbonate, TRIS, and histidine were equally effective in maintaining intracellular pH close to control values during arrest. Conversely, the use of glutamate resulted in a more pronounced fall in intracellular pH, which correlated with a better preservation of adenosine triphosphate and a better functional recovery than in the other groups. Overall, the greatest extent of preservation was provided by the pH 7.00 glutamate-containing cardioplegic solution. We conclude that additional protection can be conferred to the cold, chemically arrested heart by combining mild intracellular acidosis, which lowers metabolic needs during arrest, most likely through a limitation of calcium overload, and provision of glutamate, which may act as a substrate for anaerobic energy production while allowing intracellular pH to be kept within the appropriate range.     

Functional and metabolic effects of nicardipine on ischemic rat hearts with multidose potassium cardioplegia

This study was undertaken to assess the effect of a calcium antagonist, nicardipine (N), added in a cardioplegic solution on the ischemic myocardium. Isolated rat hearts were perfused with oxygenated Krebs Ringer Bicarbonate (KRB) solution by Langendorff's perfusion method and were subjected to 2 hours of ischemic arrest at 30 degrees C with multidose cardioplegia (every 30 min, for 5 min) and a subsequent 60 min of reperfusion. HR, LVP, coronary flow and oxygen tension of coronary effluent were monitored. Oxygen saturation of intracellular myoglobin and redox state of mitochondrial cytochrome aa3 in the myocardial cell were continuously measured throughout studies by a spectrophotometer. Oxygenated crystalloid cardioplegic solution (KRB) containing 25 mM of potassium was used. 40 rats were divided into 4 groups (10 rats each) according to the concentration of N (none, 0.5, 1 and 2 mg/L) in fully oxygenated potassium cardioplegic solution (PO2: 601 +/- 31 mmHg). The percent recovery of pressure-rate product after reperfusion was compared in each group and the optimal concentration of N was found to be 1 mg per liter of cardioplegic solution. No significant difference was found between Group Ia (N = 0 mg/L) and Group Ib (N = 1 mg/L) in metabolic or hemodynamic recovery after reperfusion. In other experiments, 40 rats in Group IIa (N = 0 mg/L, n = 20) and Group IIb (N = 1 mg/L, n = 20) received 10 ml of poorly oxygenated cardioplegic solution (PO2: 215 +/- 10 mmHg) on each reinfusion followed by a 25 min interval of ischemic arrest. The index of oxygen utilization, MVO2/pressure-rate product after reperfusion was significantly lower in Group IIb than in Group IIa (p less than 0.05). The results show that the addition of N (1 mg/L) to the cardioplegic solution preserved a more aerobic state (higher intracellular oxygen level) in the myocardium by further suppressing myocardial oxygen demand during the ischemic period which resulted in better myocardial protection. Therefore, it is concluded that the addition of N to the cardioplegic solution enhances myocardial preservation during myocardial ischemia.     

Persistent atrial activity during cardioplegic arrest: a possible factor in the etiology of postoperative supraventricular tachyarrhythmias

We assessed the relationship between the duration of atrial activity during the cross-clamp period and the postoperative occurrence of supraventricular tachyarrhythmias in 50 patients undergoing elective coronary bypass operation. The atrial electrical activity was monitored continuously by means of a bipolar atrial electrogram from the onset of cardioplegic administration until removal of the aortic cross-clamp. While ventricular arrest was induced promptly and maintained in all patients, sustained atrial activity was observed in 44 out of 50 patients during the cross-clamp period. In the postoperative period, supraventricular tachyarrhythmias developed in 15 patients (Group 1). Thirty-five patients (Group 2) were free from such tachyarrhythmias. There was no significant difference between the two groups with respect to cross-clamp time, bypass time, amount of cardioplegic solution used, or number of grafts per patient. The mean duration of atrial activity during cardioplegic arrest, however, was significantly longer in Group 1 than in Group 2 (46 +/- 4.7 minutes versus 22.6 +/- 4.0 minutes, respectively, p less than 0.001). None of the 6 patients in whom atrial activity was completely abolished experienced supraventricular tachyarrhythmias. The strong correlation observed between the duration of atrial activity during cardioplegic arrest and the incidence of postoperative supraventricular tachyarrhythmias suggests the possibility that these arrhythmias may be a manifestation of inadequate atrial protection during global myocardial ischemia.     

Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery?

OBJECTIVE: Intermittent antegrade blood cardioplegia (IABC) has been standardized as a routine technique for myocardial protection in coronary surgery. However, if the myocardium is known to tolerate short periods of ischemia during hypothermic arrest, it may be less tolerant of warm ischemia, so the optimal cardioplegic temperature of intermittent antegrade blood cardioplegia is still controversial. The aim of this study was to compare the effects of warm intermittent antegrade blood cardioplegia and cold intermittent antegrade blood cardioplegia on myocardial pH and different parameters of the myocardial metabolism. METHODS: Thirty patients undergoing first-time isolated coronary surgery were randomly allocated into two groups: group 1 (15 patients) received warm (37 degrees C) intermittent antegrade blood cardioplegia and group 2 (15 patients) received cold (4 degrees C) intermittent antegrade blood cardioplegia. The two randomization groups had similar demographic and angiographic characteristics. Total duration of cardiopulmonary bypass (108+/-17 and 98+/-21 min) and of aortic cross-clamping (70+/-13 and 65+/-15 min) were similar. The cardioplegic solutions were prepared by mixing blood with potassium and infused at a flow rate of 250 ml/min for a concentration of 20 mEq/l during 2 min after each anastomosis or after 15 min of ischemia. Intramyocardial pH was continuously measured during cardioplegic arrest by a miniature glass electrode and values were corrected by temperature. Myocardial metabolism was assessed before aortic clamping (pre-XCL), 1 min after removal of the clamp (XCL off) and 15 min after reperfusion (Rep) by collecting coronary sinus blood samples. All samples were analyzed for lactate, creatine kinase (MB fraction), myoglobin and troponin I. Creatine kinase and troponin I were also daily evaluated in peripheral blood during 6 days post-operatively. RESULTs: The clinical outcomes and the haemodynamic parameters between the two groups were identical. In group 1, XCL off and Rep were associated with higher coronary sinus release of lactate (5.5 +/- 1.8 and 2.2 +/- 0.5 mmol/l) than in group 2 (2.0 +/- 0.7 and 1.6 +/- 0.3 mmol/l, P < 0.05). Mean intramyocardial pH was lower in group 1 (7.23 +/- 0.08) than in group 2 (7.65 +/- 0.30, P < 0.05). There were no significant differences between the two groups with respect of creatine kinase (MB fraction) either after Rep or during the post-operative period. Lower coronary sinus release of myoglobin was detected at Rep in group 1 (170 +/- 53 microg/l) than in group 2 (240 +/- 95 microg/l, P < 0.05). At day 1, a lower release of troponin I was found in group 1 (0.11 +/- 0.07 g/ml) compared to group 2 (0.17 +/- 0.07 ng/ml, P < 0.05). CONCLUSION: With regards to similar clinical and haemodynamic results, myocardial protection induced by warm IAEX is associated with more acidic conditions (intramyocardial pH and lactate release) and less myocardial injury (myoglobin and troponin I release) than cold intermittent antegrade blood cardioplegia during coronary surgery.     

Superiority of retrograde cardioplegia after acute coronary occlusion

Because antegrade cardioplegia may limit the distribution of cardioplegia beyond a coronary occlusion, this study was undertaken to determine whether retrograde coronary sinus cardioplegia provides superior myocardial protection during revascularization of an acute coronary occlusion. In 20 adult pigs, the second and third diagonal branches were occluded with a snare for 1 1/2 hours. Animals were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic arrest with multidose, potassium, crystalloid cardioplegia. In 10 animals, the cardioplegia was given antegrade through the aortic root, whereas in 10 others, it was given retrograde through the coronary sinus. After the arrest period, the coronary snares were released and all hearts were reperfused for 3 hours. Postischemic damage in the myocardium beyond the occlusions was assessed by wall motion scores using two-dimensional echocardiography (4 = normal to -1 = dyskinesia), the change in myocardial pH from preischemia, and the area of necrosis/area of risk (histochemical staining). Hearts protected with retrograde coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/- 0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/- 0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/- 3.6% versus 73.3% +/- 3.5%; p less than 0.0001). We conclude that retrograde coronary sinus cardioplegia provides more optimal myocardial protection than is possible with antegrade cardioplegia after revascularization of an acute coronary occlusion.     

Intracellular free calcium accumulation in ferret vascular smooth muscle during crystalloid and blood cardioplegic infusions.

OBJECTIVE: The effects of magnesium- and potassium-based crystalloid and blood-containing cardioplegic solutions on coronary smooth muscle intracellular free calcium ([Ca2+]i) accumulation and microvascular contractile function were examined. METHODS: Isolated ferret hearts were subjected to hyperkalemic (25 mmol/L K+) blood cardioplegic infusion, hypermagnesemic (25 mmol/L Mg2+, K+-free) crystalloid cardioplegic infusion, or hyperkalemic crystalloid cardioplegic infusion for 1 hour. Coronary arterioles were isolated, cannulated, and loaded with fura 2. Reactivity and [Ca2+]i were assessed with videomicroscopy. [Ca2+]i was measured at baseline and after application of 50 mmol/L KCl. In addition, [Ca2+]i and vascular contraction were measured during exposure to Mg2+ and K+ cardioplegic solution at both 4 degrees C and 37 degrees C. RESULTS: From a baseline [Ca2+]i of 177 +/- 52 nmol/L, K+ cardioplegic infusion (302 +/- 80 nmol/L potassium) markedly increased [Ca2+]i, whereas blood cardioplegic infusion (214 +/- 53 nmol/L) and Mg2+ cardioplegic infusion (180 +/- 42 nmol/L) did not alter [Ca2+]i. Although a difference between groups in percentage contraction after application of 50 mmol/L KCl was not observed, [Ca2+]i increased significantly more in vessels in the control group (764 +/- 327 nmol/L) and the K+ crystalloid cardioplegic infusion group (698 +/- 215 nmol/L) than in vessels in the blood cardioplegic infusion group (402 +/- 45 nmol/L) and the Mg2+ cardioplegic infusion group (389 +/- 80 nmol/L). Mg2+ cardioplegic solution induced no microvascular contraction at either 4 degrees C or 37 degrees C, nor was an increase in [Ca2+]i observed. K+ cardioplegic solution induced microvascular contraction at 37 degrees C but not at 4 degrees C; it increased [Ca2+]i at both 4 degrees C and 37 degrees C. CONCLUSION: An Mg2+-based cardioplegic solution, or appropriate Mg2+ or blood supplementation of a K+ crystalloid cardioplegic solution, may decrease the accumulation of [Ca2+]i in the vascular smooth muscle during ischemic arrest.     

Effect of coronary artery occlusion on myocardial protection by retroperfusion of cardioplegic solutions

Coronary artery stenoses impede delivery of cardioplegic solutions infused through the aortic root. Therefore, the efficacy of retroperfusion of cardioplegic solution through the coronary sinus was assessed in dogs subjected to cold, potassium cardioplegic arrest. Group I (N = 15) had the left anterior descending (LAD) coronary artery occluded throughout ischemia while Group II (N = 15) had a patent LAD. Transmural biopsies of both the left ventricular (LV) apex and right ventricle (RV) were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). Regional wall temperatures were sequentially monitored. The time from aortic cross-clamping to electrical arrest varied widely, but the mean arrest time of each group was similar (174 +/- 22 vs 175 +/- 28 sec). (table; see text) Comparable depletion of ATP stores (vs preischemia) occurred in each ventricle regardless of coronary artery patency. Similarly, CP stores were depleted 60-72% (P less than 0.01) during ischemia. Mean temperatures during arrest of the RV and LV (17.2-19.5 degrees C) did not differ and were not affected by LAD occlusion. Coronary venous resistance remained constant with repetitive infusions. These data suggest that myocardial protection with coronary sinus retroperfusion is independent of arterial patency, but is suboptimal, perhaps due to the prolonged time needed to induce ventricular arrest.     

Continuous versus intermittent cardioplegia in the presence of a coronary occlusion

Coronary artery occlusions can alter the distribution of cardioplegia and result in ischemic damage. This study was undertaken to determine whether continuous antegrade cardioplegia delivery would result in colder temperatures and provide better washout of acid metabolites than is possible with intermittent antegrade cardioplegia when coronary occlusions are present. Twenty pigs were placed on cardiopulmonary bypass and underwent 2 hours of ischemic arrest with occlusion of the middle left anterior descending coronary artery followed by 1 hour of reperfusion without occlusion of that artery. Ten pigs received intermittent (every 20 minutes) antegrade potassium crystalloid cardioplegia (4 degrees C), and 10 others had the same solution given continuously (30 mL/min). Cardioplegia distribution was assessed by continuous monitoring of myocardial pH (Khuri pH probe) and temperature in the region beyond the occlusion of the left anterior descending coronary artery. Both cardioplegic techniques resulted in tissue acidosis (continuous group, 6.69 +/- 0.08, versus intermittent group, 6.73 +/- 0.07; not significant). Average temperature in the left anterior descending coronary artery during arrest was also similar in both groups (continuous group, 18.3 degrees +/- 0.5 degrees C, versus intermittent group, 18.2 degrees +/- 0.5 degrees C). Because of these metabolic changes, both cardioplegic techniques resulted in abnormal wall motion in the anteroseptal region using two-dimensional echocardiography, but the scores were not significantly different (continuous group, 1.5 +/- 0.3, versus intermittent group, 1.6 +/- 0.4; 4 = normal to 0 = dyskinesia).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of reperfusion after acute coronary occlusion on the beating, working heart compared to the arrested heart treated locally and globally with cardioplegia

To determine whether acutely ischemic myocardium could be more effectively salvaged by reperfusion on cardiopulmonary bypass (CPB) in the cardioplegia-treated heart than with reperfusion in the beating, working heart, 52 greyhound dogs underwent 3 hours of left anterior descending (LAD) occlusion and were randomly assigned to one of four groups. In Group I (19 dogs) the LAD occlusion was released at 3 hours and reperfusion continued in the beating, working heart for an additional 3 hours. Group II (six dogs), Group III (14 dogs), and Group IV (13 dogs) were placed on CPB and underwent 45 minutes of hypothermic ischemic arrest protected by aortic root potassium cardioplegia. In Group II, only aortic root potassium cardioplegia was given; in Group III, the ischemic area was perfused with potassium cardioplegic solution via a graft from the internal mammary artery (IMA) to the LAD. In Group IV, blood cardioplegic solution via the IMA-LAD graft was used. After the cross-clamp and local occlusion were removed, CPB was discontinued after an additional 45 minutes and reperfusion was continued off CPB for an additional 1 1/2 hours (total 6 hours). The ischemic area at risk was determined by injecting monastryl blue dye via the left atrium while the LAD was briefly reoccluded. After the animal had been sacrificed and the left ventricle had been sectioned, the area of myocardial necrosis was determined by nonstaining with triphenyltetrazolium chloride (TTC). For each group, the ratios of area of necrosis/area at risk (AN/AR) were calculated and postreperfusion arrhythmias were documented. Postreperfusion arrhythmias were noted in 11 of 12 animals in the beating, working heart group and only two of 24 in the combined CPB groups. The mean AN/AR was 66% +/- 2% in the beating, working heart (Group I), 59% +/- 6% after infusion of potassium cardioplegic solution into the aortic root (Group II), 57% +/- 6% with blood cardioplegia (Group IV), and 38% +/- 6.5% after global and local application of the potassium cardioplegic solution into the ischemic area (Group III). This study suggests that the reperfused ischemic myocardium will sustain less necrosis and less postreperfusion arrhythmias when the heart is protected by global and local cold potassium cardioplegia on CPB.     

Heparin-Bonded Circuits Decrease Myocardial Ischemic Damage: An Experimental Study

Background. Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization.

Methods. In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits.

Results. Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 ± 0.3 versus 2.3 ± 0.2; 4 = normal to −1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = −0.31 ± 0.02 versus −0.64 ± 0.08; p < 0.05), smallest increase in lung H₂O (1.7% ± 0.7% versus 6.1% ± .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% ± 2.2% versus 40.4% ± 1.6%; p < 0.05).

Conclusions. We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.