Cardioplegic Induction Research Articles

Myocardial metabolism during aortic valve replacement. III. Continuous infusion of cold blood for cardioplegia.

Myocardial energy metabolism during hypothermic potassium cardioplegia with blood as the cardioplegia vehicle was studied in eight patients undergoing aortic valve replacement. Cardiac arrest was induced with a single bolus infusion and maintained by continuous perfusion. Myocardial biopsies were taken from the left ventricle 10 min after aortic cross-clamping (a.c.) and immediately before declamping (d.c.) and were analyzed for ATP, creatine phosphate (CP), creatine (C) and lactate. The interindividual range of myocardial temperature was 15-21 degrees a.c. and 17-22 degrees C immediately before d.c. The ATP concentration decreased (12.7 +/- 3.9-10.4 +/- 3.5 mmol X kg-1 dry muscle), the lactate concentration increased (102 +/- 30-156 +/- 8 mmol X kg-1 d.m.), and the total creatine (CP + C) remained constant. Induction of cardioplegia by blood resulting in a mean myocardial temperature of 19 degrees C could not prevent anaerobic metabolism. The changes in ATP levels between 10 min after a.c. and just before d.c. were small, however, indicating that oxygen delivery during continuous blood cardioplegia at a myocardial temperature of c. 20 degrees C prevented further loss of ATP. The lactate concentration, however, increased markedly between 10 min after a.c. and d.c., demonstrating that a significant proportion of the total metabolism was anaerobic.

Coronary Artery Bypass Graft Surgery: Clinical Comparison of Cold Blood Potassium Cardioplegia, Warm Cardioplegic Induction, and Secondary Cardioplegia

An analysis of myocardial protection was performed in 45 low-risk patients undergoing coronary bypass procedures who were divided into three equal groups with similar preoperative ejection fractions and coronary artery obstructions. Group 1 (N = 15) received cold blood cardioplegia, Group 2 received cold blood cardioplegia and secondary cardioplegia, and Group 3 received cold blood cardioplegia plus warm cardioplegic induction. The aortic cross-clamp time and the number of bypass grafts were similar among the groups. The following variables were measured serially: electrocardiographic changes, serum myocardial-specific isoenzyme of creatine kinase, cardiac output, left ventricular filling pressure, ejection fraction, and left ventricular wall motion. The three methods evaluated were all effective in protecting the myocardium during global myocardial ischemia. Patients who received secondary cardioplegia (Group 2) were more likely to exhibit spontaneous defibrillation (12/15) than those in Group 1 (5/15) or Group 3 (6/15) ( p < 0.05). However, measurements of left ventricular performance and evidence of perioperative myocardial infarction were similar among all three groups. These data suggest that a standard technique of cold potassium cardioplegia alone should be the method of choice in elective, low-risk coronary bypass operations rather than this technique in combination with either of the other two more costly and complex methods evaluated in this study.

ADENINE NUCLEOTIDE DEGRADATION IN THE HUMAN MYOCARDIUM DURING CARDIOPLEGIA: 200

Myocardial ischemia is associated with adenine nucleotide degradation and accumulation of nucleosides and bases. Data regarding adenine nucleotide degradation in ischemic human myocardium is limited. The adenine nucleotides, IMP, adenosine, inosine, hypoxanthine and uric acid were determined by high pressure liquid chromatography, in biopsies (1.5-4 mg) from human left ventricular myocardium during cardioplegia (at 10-15°C) in six patients (aged 35-64 year) subjected to aortic valve replacement surgery. The study was performed after informed consent and approval from the Ethics Commité. The first biopsy was collected after induction of cardioplegia and the second 45-60 min later. The myocardium was perfused with diluted cold blood 25-30 ml/min (with 20 mM potassium). The ATP concentration was 12.64±1.96 mmoles/kg dry muscle (d.m.) after induction and decreased by 37±5% (p<0.01). AMP ranged between 2 and 3 mmoles/kg d.m., while IMP was consistently low, (0.11±0.01 mmoles/kg d.m.). The adenosine concentration was high, (0.26±0.04 mmol/kg d.m.), and inosine increased from 0.82 to 2.66 mmoles/kg (p<0.01). Approximately 3 mmoles/kg d.m. of purine material was probably washed out of tissue during the perfusion. In conclusion, cardioplegia is associated with severe ischemia and the major route fo AMP degradation is probably through adenosine.

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.

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.

Amelioration of the effects of ischemic cardiac arrest by the intracoronary administration of cardioplegic solutions.

Interruption of coronary flow during cardiac surgical procedures provides a bloodless flaccid heart and allows precise and rapid correction of complex cardiac defects. However, myocardial damage occurs in direct proportion to the duration of the ischemia. As the induction of cardioplegia simulataneous with the initiation of cardiac ischemia helps to preserve cardiac energy reserves and thus myocardial integrity, the identification of a consistently reliable cardioplegic technique is desirable. Isolated perfused working rat hearts were made ischemic for one hour by aortic cross-clamping and were compared with hearts rendered cardioplegic at the onset of ischemia by the intracoronary administration of 5 ml of a hypothermic solution: 1) Krebs-Henseleit buffer, 2) Ringer's lactate, 3) tetrodotoxin, 4) potassium chloride, or 5) potassium citrate. Cardiac output, heart rate, aortic pressure and coronary flow were determined pre and post-ischemia. When compared to time-matched controls and hearts arrested with potassium or tetrodotoxin, the ischemia and ischemia-Ringer's lactate groups showed significant post cross-clamp depression of all measured parameters. Intracoronary Ringer's lactate, although often used as an adjunct to ischemic arrest, was not of significant value. In contrast, hearts arrested with tetrodotoxin, potassium chloride or potassium citrate showed no significant post-ischemic functional or histologic deficit. Perfusion with hypothermic Krebs-Henseleit buffer protected the myocardium better than did Ringer's lactate but less well than the tetrodotoxin or isotonic high potassium solutions. The induction of hypothermic metabolic arrest of the heart by briefly perfusing the coronary arteries via the aortic root with isotonic buffered solutions results in markedly improved myocardial tolerance to one hour of ischemia and avoids the problems of low cardiac output and ventricular irritability previously reported with hypertonic potassium citrate arrest.