Blood Cardioplegic Solution Research Articles

Ectothermic philosophy of acid-base balance to prevent fibrillation during hypothermia.

In the ectotherms, or cold-blooded animals, carbon dioxide pressure decreases (PCO2) and pH increases as body temperature falls. This tends to increase coronary blood flow and prevent fibrillation. This concept was investigated in 181 consecutive patients undergoing open heart surgery of all types. In 121 cases, endothermic (warm-blooded) temperature-corrected normal values of pH, PCO2, and oxygen pressure were maintained during extracorporeal circulation as the perfusate temperature was lowered to 24 degrees C prior to aortic cross-clamping and administration of blood cardioplegia solution. In 49 patients (40%), ventricular fibrillation occurred prior to cross-clamping. In the other 60 consecutive cases, in which the ectothermic principle of cooling was applied, the PCO2 was allowed to decrease from 50 to 40 mm Hg and the non-temperature-corrected pH rose from 7.28 to 7.42. Fibrillation occurred in only 12 (20%) of these 60 patients.

236 大動脈弁閉鎖不全症(AR)における心筋保護法の検討

236 大動脈弁閉鎖不全症(AR)における心筋保護法の検討

Immediate functional recovery and avoidance of reperfusion injury with surgical revascularization of short-term coronary occlusion.

Functional recovery with surgical revascularization of acutely ischemic myocardium has not been compared with its nonsurgical counterpart in experimental preparations of coronary occlusion. This study compares the functional and metabolic recovery of ischemic (1 hr coronary occlusion) segments revascularized either by restoration of coronary patency (simulating nonsurgical recanalization, e.g., angioplasty) or by surgical revascularization with multidose hypothermic potassium blood cardioplegic solution. Twenty-two anesthetized open-chest dogs were instrumented with Millar micromanometer-tip catheters to measure left ventricular and aortic pressures. Piezoelectric ultrasonic dimension gauges were implanted in the subendocardium supplied by the left anterior descending coronary artery to measure segmental contractile function. In five dogs, only biopsy samples were obtained for control measurements of ATP, creatine phosphate, and tissue water content. In the remaining 17 dogs, the left anterior descending artery and collaterals were ligated for 1 hr. The ligatures were removed in eight dogs and coronary perfusion continued for 2 hr, simulating nonsurgical reperfusion. The remaining nine dogs were placed on cardiopulmonary bypass and the hearts were arrested for 1 hr with multidose (every 20 min) blood cardioplegic solution enhanced with glutamate and aspartate, simulating surgical revascularization (coronary artery bypass grafting). The coronary ligatures were not released until the second cardioplegic infusion, simulating graft placement. One hour of coronary occlusion placed 39.4 +/- 2.5% of the left ventricle at risk, and converted active systolic shortening to persistent paradoxical bulging (25.2 +/- 2.2% to -5.8 +/- 1.2% systolic shortening).(ABSTRACT TRUNCATED AT 250 WORDS)

CLINICAL EVALUATIONS OF COLD YOUNG'S AND HIGH POTASSIUM AND HIGH MAGNESIUM SOLUTION IN 636 OPEN HEART PATIENTS

Six hundred thirty-six patients underwent open heart surgery under myocardial protection with cold Young's and high potassium (K+: 20mEq/l) and high magnesium (Mg++: 24.1mEq/l) cardioplegia at Sapporo Medical College and Hospital between May 1980 and September 1984. We classified the procedure of myocardial protection into three stages as follows: Stage I: To obtain cardiac arrest as soon as possible so as to reduce the high-energy phosphates in the myocardium. Stage II: To keep the myocardium in a hypothermic stage, to use membrane stabilization (K+, Mg++), to prevent acidosis and edema (pH and osmotic pressure), and to give chemical substances (CoQ10, Anti Ca++). Stage III: To prevent reperfusion injury (minimum differences between the heart and the reperfusate blood temperature, low flow and low pressure). We also had the advantage of developing new equipment and instruments for these procedures. In this study, the maximum periods of ischemic arrest, as long as four hours, have been well tolerated, and there were 22 hospital deaths out of 636 patients, i.e., 3.5% mortality. However, there were also 48 patients who had aortic cross-clamping time prolonged to two hours and had higher incidences of postoperative low cardiac output syndrome than the other patients undergoing this procedure. We are now planning to use cold blood cardioplegic solution in elective patients who are suspected before surgery to require prolonged arotic cross-clamping time.

The use of perfluorochemicals during open heart surgery.

Several experimental studies of global myocardial ischemia involving different animal models have demonstrated enhanced oxygen delivery and oxygen consumption when oxygenated perfluorochemical cardioplegic solutions were used. Use of these solutions results in improved recovery of ventricular function after prolonged periods of global ischemia when compared with either standard crystalloid cardioplegic solutions or oxygenated blood cardioplegic solutions. Furthermore, intracellular pH and myocardial ATP levels are well maintained during protracted periods of global myocardial ischemia with oxygenated perfluorochemical cardioplegic solutions. Based on these convincing experimental results, clinical investigation of an oxygenated perfluorochemical cardioplegic solution is warranted. Although current methods of myocardial protection during open heart surgery usually are adequate, patients undergoing complicated open heart surgical procedures or those with significant left ventricular dysfunction prior to surgery--that is, those patients most in need of highly effective myocardial protection--would likely benefit substantially if oxygen were delivered via the cardioplegic solution. Furthermore, perfluorochemical solutions may be especially useful for cardiopulmonary bypass pump priming in patients unable to accept whole blood transfusion during open heart surgery.

Safety of prolonged aortic clamping with blood cardioplegia: II. Glutamate enrichment in energy-depleted hearts

Cold blood cardioplegic techniques are limited in their ability to protect energy-depleted hearts during aortic clamping. This study extends our previous observations on the benefits of amino acid (L-glutamate) enrichment of blood cardioplegic solutions as well as the added metabolic benefits of normothermic induction of cardioplegic arrest to increase the rate of repair of energy-depleted hearts. The results demonstrate that L-glutamate enrichment of blood cardioplegic solutions significantly improves metabolic recovery (greater oxygen consumption, better anaerobic metabolism) and ventricular performance. Normothermic induction of glutamate-enriched cardioplegia allowed complete recovery of myocardial metabolism and function compared to cold blood cardioplegic technique and may be used as a form of "active resuscitation" of energy-depleted hearts.

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.

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.

Warm induction of cardioplegia with glutamate-enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon support: Initial experience and operative strategy

This report reviews the initial clinical application of our experimental studies inducing cardioplegia with a warm (37 degrees C) glutamate-enriched blood solution in ischemically damaged hearts. Over 15 months, 23 consecutive coronary patients requiring preoperative intra-aortic balloon and inotropic drug support for cardiogenic shock underwent operation for left ventricular power failure. Twelve patients were given a warm glutamate-enriched blood cardioplegic solution during the first 5 minutes of aortic clamping before multidose cold (4 degrees C) glutamate blood cardioplegia was begun; 11 patients received standard multidose cold blood cardioplegia without glutamate. All patients had comparably depressed left ventricular performance preoperatively despite maximal inotropic and balloon support and showed evidence of extending myocardial infarction. They did not differ in the number of grafts placed (3.7 +/- 0.2), associated valve and aneurysm procedures (seven patients) or cross-clamp time (89 +/- 6 minutes). All patients received warm blood cardioplegic reperfusion before aortic unclamping. The perioperative mortality was 9% (2/23); both patients who died received cold blood cardioplegia without glutamate. In addition to lower mortality, patients receiving warm glutamate blood cardioplegia exhibited better hemodynamics, allowing earlier discontinuation of inotropic drug infusion (1.3 +/- 0.5 versus 2.7 +/- 0.8 days, p less than 0.05) and intraaortic balloon support (1.2 +/- 0.2 versus 3.6 +/- 0.5 days, p less than 0.05). Late mortality was 30%, resulting in a 65% overall survival rate (2 to 15 months) for the entire series of patients. The operative principles evolving from this early experience include (1) warm blood cardioplegic induction, (2) glutamate enrichment, (3) meticulous attention to cardioplegic distribution and grafting sequence, (4) warm cardioplegic reperfusion before unclamping, and (5) graft perfusion during construction of proximal anastomoses. Hopefully, further application of these techniques will improve results in these extremely high risk coronary patients requiring operation.

Comparison of distribution beyond coronary stenoses of blood and asanguineous cardioplegic solutions

In seven dogs on cardiopulmonary bypass, a critical stenosis (75% to 90%) of the left anterior descending coronary artery (LAD) was produced. Alternate 250 ml/min infusions of asanguineous and blood cardioplegic (4 degrees C) solutions were made for 3 to 5 minutes. Poststenotic flow (flowmeter), intramyocardial temperature, and aortic pressure were measured. During cardioplegic infusions of 250 ml/min, aortic pressure was 34 +/- 4 mm Hg higher with blood cardioplegia than with asanguineous cardioplegia (82 +/- 7 versus 48 +/- 8 mm Hg). Poststenotic cardioplegic flow was 39% +/- 9% higher (29 +/- 5 versus 18 +/- 5 ml/min) with blood cardioplegia. Consequently, blood cardioplegia resulted in more rapid arrest (20 +/- 2 versus 45 +/- 5 seconds) and lower myocardial temperature (6 degrees +/- 1 degree C) in the region of LAD blood supply; posterior ventricular myocardial cooling was similar (unobstructed vessels) with both solutions. These data show that the reduced viscosity of asanguineous cardioplegia compared to blood cardioplegia results in lower aortic pressure. Consequently, the higher aortic pressure with blood cardioplegia results in superior cardioplegic delivery beyond obstructed coronaries and better myocardial cooling. We conclude that the decreased viscosity of 4 degrees C asanguineous cardioplegia causes diversion of cardioplegic solution from the obstructed to the normal coronary bed.

The Effect of Nitroglycerin Cardioplegia on Myocardial Cooling in Patients Undergoing Myocardial Revascularization

The effect of intracoronary administration of nitroglycerin on the distribution of cardioplegia and myocardial cooling was assessed in 45 patients undergoing elective myocardial revascularization. The patients were divided into three groups. Myocardial temperature was measured over the right and left coronary artery distributions in Group 1 after the infusion of 1 liter of potassium blood cardioplegic solution (20 mEq of potassium per liter). Similar temperature measurements were made in Group 2 after the addition of 300 μg of nitroglycerin to the cardioplegic solution and in Group 3 after the addition of 1,000 μg of nitroglycerin. Nitroglycerin did not affect myocardial cooling, and large temperature gradients persisted after delivery of cardioplegia in patients with occlusive coronary artery disease. Unexpectedly, however, the rate of cardioplegia delivery increased by 134%, within the same range of infusion pressures, in patients receiving nitroglycerin. Although nitroglycerin cardioplegia does not affect the regional disparity in the distribution of cardioplegia in patients with severe coronary artery disease, intracoronary administration of nitroglycerin reduces the time required for administration of cardioplegia and thereby decreases the total ischemia time.

Simplified System for Blood Cardioplegia

A simplified delivery system for blood cardioplegia is described. The system delivers cold blood cardioplegic solution at 6° to 14°C and a hematocrit of 11 to 17%. The setup is inexpensive and easy to assemble, and can be utilized with available equipment.

Benefits of normothermic induction of blood cardioplegia in energy-depleted hearts, with maintenance of arrest by multidose cold blood cardioplegic infusions

This study tests the hypothesis that warm induction of cardioplegia prior to prolonged maintenance by multidose infusions of cold blood cardioplegic solution would increase the tolerance of energy-depleted hearts to subsequent aortic clamping. Eighty percent depletion of subendocardial adenosine triphosphate (ATP) was produced in 30 dogs by 45 minutes of normothermic ischemia. This was followed either by unmodified blood reperfusion or 2 additional hours of aortic clamping with multidose cold blood cardioplegia. We compared a brief (5 minute) period of 37 degrees C cardioplegic induction to standard 4 degrees C blood cardioplegic induction to determine if warm induction would enhance metabolic and functional recovery. Warm cardioplegic induction resulted in more oxygen consumption than cold induction (16.9 versus 8.1 cc/100 gm), and lower levels of glucose-6-phosphate (G6P), suggesting better aerobic metabolism (0.97 versus 1.87 microM/gm wet weight). Prompt repletion of creatine phosphate (CP) occurred with warm and cold cardioplegic induction, although ATP levels levels remained low. Hearts undergoing ischemia and unmodified reperfusion consumed insufficient oxygen to meet basal metabolic needs during reperfusion (7 cc/100 gm below requirement) and recovered only 33% +/- 5% of control left ventricular performance. Better function occurred with cold cardioplegic induction (63% +/- 5%), and almost complete recovery (85% +/- 5%) occurred when warm induction of cardioplegia was used. We conclude that warm induction followed by prolonged cold multidose blood cardioplegic arrest enhances aerobic metabolism, results in normal left ventricular performance, and improves tolerance of aortic clamping in energy-depleted hearts.

Use of cold blood cardioplegia to protect against coronary microcirculatory injury due to ischemia and reperfusion

The effect of cold blood cardioplegia in preventing microvascular injury owing to myocardial ischemia and reperfusion was studied. Two groups of eight dogs each were placed on cardiopulmonary bypass with separate coronary perfusion at 80 mm Hg. Microcirculatory function was assessed by measuring the extraction and permeability surface area product (PS) for inulin and albumin. These changes were correlated with the transport and extraction of oxygen, coronary blood flow, and morphologic studies of the microvasculature. In Group I, ischemic hearts were kept normothermic for 45 minutes. In Group II, 250 ml of cold (4 degrees C) blood cardioplegic solution (potassium chloride 30 mEq/L) was infused and the infusion repeated at 15 and 30 minutes. Reperfusion resulted in marked reactive hyperemia for Group I (p less than 0.05) but no hyperemic response in Group II. In Group I, but not II, ischemia-reperfusion caused a significant decrease in PS inulin (0.47 +/- 0.10 ml/min/gm) compared to the preischemic value (1.04 +/- 0.23) (p less than 0.05). There was a threefold decrease in the PS inulin/PS albumin ratio with reperfusion in Group I, indicating increased vascular permeability to albumin. There was also a significant decrease in myocardial oxygen consumption (from 5.1 +/- 0.7 to 3.4 +/- 0.5 ml/min/100 gm, p less than 0.05) for Group I. These did not decrease for Group II. Histologic studies showed diffused areas of no reflow in the unprotected hearts. The wet/dry weight ratio for Group I (4.97 +/- 0.09) was significantly greater than for Group II (4.49 +/- 0.07) (p less than 0.001). The results indicate that in the unprotected heart, ischemia-reperfusion caused microcirculatory injury resulting in increased permeability to albumin, edema, a reduction in surface area, and areas of no reflow. In contrast, in the hearts protected with cold blood cardioplegia, no evidence of microcirculatory injury occurred.

Critical importance of ensuring cardioplegic delivery with coronary stenoses

This study examines the relative importance of the duration of ischemia versus the adequacy of cardioplegic distribution and protection in hearts with coronary stenoses. Of 18 dogs on cardiopulmonary bypass, 12 underwent critical narrowing (greater than 90%) of the left circumflex artery (LCA) and total occlusion of the anterior descending coronary artery (LAD). In six dogs (control) the coronary arteries were patent. A 16 degrees C blood cardioplegic solution was given at 20 minute intervals of aortic clamping. In control dogs and in six dogs with stenoses, the aorta was clamped for 60 minutes. In the latter group, the stenoses were removed after 20 and 40 minutes to simulate sequential completion of grafts and better cardioplegic distribution. In the remaining dogs with stenoses, the aorta was clamped for only 30 minutes, with stenoses removed after the heart had been returned to the beating empty state for 30 minutes to simulate doing distal grafts with cardioplegic protection and proximal grafts during reperfusion (traditional technique). With sequential grafting, myocardial temperature was lower (16 degrees C versus 22 degrees C) and incidence of reperfusion fibrillation less than with the traditional technique. Despite a greater ischemic interval, sequential grafting with adequate cardioplegic distribution resulted in less lactate washout (5 +/- 15 versus 35 +/- 6 cc/100 gm/min), greater recovery of compliance, and higher stroke work indices (1.32 +/- 0.12 versus 0.75 +/- 0.15 kg-m/min). We conclude that the success of myocardial protection with potassium cardioplegia in hearts with coronary stenoses is related more to ensuring its distribution than to limiting the duration of ischemic arrest with the false assumption that the heart is reperfused adequately while proximal grafts are completed in the beating empty state.

Myocardial energy replenishment and reversal of ischemic damage by substrate enhancement of secondary blood cardioplegia with amino acids during reperfusion

Twenty-five dogs underwent 45 minutes of normothermic ischemic arrest. Fifteen minutes after unclamping, no heart could support the systemic circulation. In all dogs, we prolonged bypass for 30 minutes in the beating empty state. In 15 dogs, we reclamped the aorta for 10 minutes and further lowered oxygen demands by the continuous infusion of a 37° C blood cardioplegic solution (K + 30 mEq/L, pH 7.6, Ca ++ I mEq/L). In 10 of these dogs, we added L-glutamate (0.026M) to the blood cardioplegic solution. Coronary blood flow (microspheres), metabolism (oxygen content plus ATP), left ventricular compliance (intraventricular balloon), and left ventricular performance (balloon and Starling curves) were measured during control and at 15 and 45 minutes after unclamping. During rearrest, postischemic hearts treated with L-glutamate showed the highest oxygen uptake (2.25 cc/100 gm/min)* and the best recovery of adenosine triphosphate (ATF) (75%).* In the working state, 45 minutes after unclamping, the hearts receiving L-glutamate were better able to augment left ventricular subendocardial flow (85% versus 47%)* and oxygen uptake (108% versus 83%).* Consequently, they had greater recovery of the rate of contraction, +dP/dt (83% versus 72%),* and relaxation, —dP/dt (83% versus 71%),* and the highest stroke work index (1.20 versus 0.74 gm-m/kg).* Rearresting the postischemic heart with a blood cardioplegic solution containing L-glutamate results in nearly complete reversal of ischemic damage. We suspect that L-glutamate increases postischemic ATP production by stimulating oxidative metabolism through replenishment of Kreb cycle intermediates lost during ischemia.

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.