phosphocreatinine and Coronary-Disease

The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion.. In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg.kg-1 intraperitoneal) and controls during a 45 min left coronary artery occlusion and 60 min reperfusion. In separate groups of animals, haemodynamic measurements were taken at baseline, during ischaemia, and during reperfusion. Infarct size was determined by staining with triphenyltetrazolium chloride.. Female Sprague-Dawley rats were used (control group n = 25, experimental group n = 24).. Infarct size was significantly reduced in the verapamil group compared to controls: 9.9(SEM 2.3)%, n = 19 v 28.5(2.7)%, n = 19, p less than 0.001 (infarct % of left ventricular mass). Myocardial phosphocreatine and ATP levels were reduced to similar levels in both verapamil and control animals after 45 min ischaemia: 56.8(3.4)%, n = 10, v 61.4(1.8)%, n = 11 NS; 67.7(2.7)%, n = 10 v 69.7(2.9)%, n = 11, NS (% of baseline value). After 60 min reflow, there was significant recovery of phosphocreatine [91.1(4.2)% of baseline, p less than 0.05] and ATP [86.8(2.7)% of baseline, p less than 0.05] in the verapamil group, but no recovery of high energy phosphates in controls [66.3(2.8), NS; 69.6(2.7), NS]. The left ventricular systolic pressure, heart rate, rate-pressure product, and maximum rate of left ventricular pressure development were similar prior to ischaemia, and during ischaemia in both groups. There was an inverse correlation between infarct size and the degree of phosphocreatine recovery after 60 min of reperfusion (PCr recovery (%) = -0.99 x infarct size (%) + 101; r = 0.91; p less than 0.01; n = 14). Furthermore, in a separate group of animals (n = 9), there was a significant correlation between the size of the ischaemic area at risk and the degree of phosphocreatine decline after 15 min of coronary occlusion (PCr reduction (%) = 0.91 x risk area (%) + 5.6; r = 0.97; p less than 0.01).. Pretreatment with verapamil extends the ischaemic time after which reperfusion results in myocardial salvage in this model of ischaemia and reperfusion. This protective effect is independent of the haemodynamic determinants of myocardial oxygen demand and the degree of ATP and phosphocreatine depletion during the ischaemic period. In this model of reversible ischaemia, 31P magnetic resonance spectroscopy is useful for quantitating both the size of the ischaemic region during coronary artery occlusion and infarct size after reperfusion.

Topics: Adenosine Triphosphate; Animals; Calcium; Coronary Circulation; Coronary Disease; Female; Hemodynamics; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Myocardial Reperfusion; Phosphocreatine; Rats; Rats, Inbred Strains; Verapamil

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.

Topics: Adenosine Triphosphate; Animals; Bicarbonates; Buffers; Calcium; Calcium Chloride; Cardioplegic Solutions; Coronary Disease; Cryopreservation; Dose-Response Relationship, Drug; Female; Heart; Hydrogen-Ion Concentration; In Vitro Techniques; Intracellular Fluid; Magnesium; Magnetic Resonance Spectroscopy; Male; Myocardial Reperfusion Injury; Myocardium; Organ Preservation; Phosphocreatine; Phosphorus; Potassium Chloride; Sodium Chloride; Swine

Topics: Adenosine Triphosphate; Coronary Disease; Humans; Myocardium; Phosphocreatine

Ultrastructural changes in normal and hypertrophied dog hearts under conditions of total ischemia were studied by electron microscope method. In the control group sings of irreversible damage appeared in 90 min, in the presence of phosphocreatine, 10 mM, these changes became apparent in 120 min. In the hypertrophied hearts signs of the irreversible damages became evident in 60 and 90 min in the absence and presence of phosphocreatine, respectively. Ability of phosphocreatine to protect both normal and hypertrophied myocardium allows to use it safely.

Topics: Animals; Cardiomegaly; Cardioplegic Solutions; Coronary Disease; Dogs; Heart; Heart Arrest, Induced; Microscopy, Electron; Myocardium; Phosphocreatine; Time Factors

The effect of phosphocreatine and phosphocreatinine disodium salts on excitation conduction in acute myocardial ischemia was investigated, using repeated short-term ischemia exposures of the isolated rabbit ventricular septum as a model. Considerable improvement of excitation conduction through ischemized myocardium, seen after the administration of phosphocreatine and phosphocreatinine salts, was shown to be associated with Na+ added to the perfusion medium. Phosphocreatine and phosphocreatinine effects on excitation conduction time and the septal force in control perfusion were related to both the addition of Na+ and the binding of Ca2+ by these agents in the perfusion medium.

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Calcium; Coronary Disease; Culture Media; Electric Stimulation; Heart Conduction System; In Vitro Techniques; Male; Phosphocreatine; Rabbits; Sodium

Using isotope-labeled microspheres (diameter 15 microns) it was shown that phosphocreatine at a dose of 300 mg/kg does not affect the myocardial blood flow in the ischemic zone during acute occlusion (5 min) of the left anterior descending coronary artery (LAD) in dogs. Intravenous administration of NaCl hypertonic solution which contained the same amount of Na+ as 300 mg/kg of phosphocreatinine disodium salt prevented the development of ventricular fibrillation during acute LAD occlusion in dogs. Under these conditions excitation conduction velocity significantly increased. Experiments in isolated intraventricular rabbit septum have showed that the addition of phosphocreatine or phosphocreatinine to the perfusion medium at a concentration of 10 mmole/liter increased excitation conduction velocity in ischemic myocardium. However, when changes in perfusate Na+ and Ca2+ concentration produced by addition of phosphocreatine or phosphocreatinine were compensated, these compounds do not affect excitation conduction velocity. On the other hand, the alterations similar to those produced by the addition of phosphocreatine or phosphocreatinine led to the same increase of excitation conduction velocity. The results obtained indicate an important role of the changes of blood plasma ionic composition on intravenous administration of phosphocreatine in electrophysiological and antiarrhythmic effects of this substance during acute myocardial ischemia.

Topics: Acute Disease; Animals; Blood Pressure; Calcium; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Heart; Heart Rate; In Vitro Techniques; Myocardial Contraction; Phosphocreatine; Reference Values; Sodium

Changes in the content of lysophosphoglycerides in a crude plasmalemmal fraction of canine heart during short-term ischemia (occlusion of the left descending coronary artery for 8 min) have been studied in the presence and in the absence of phosphocreatine and phosphocreatinine. In the control experiments without PCr or PCr-nine ischemia caused significant elevation of the content of LPG: that of lysophosphatidylcholine was increased by 83% and that of lysophosphatidylethanolamine by 168%. Intravenous administration of PCr and PCr-nine in doses of 300 mg/kg completely prevented accumulation of LPG in the ischemic zone. Because of the well-known arrhythmogenic properties of LPG, the inhibitory effect of PCr and PCr-nine on the elevation of their concentration in the ischemic zone may be closely related to the antiarrhythmic action of PCr and PCr-nine in acute myocardial ischemia.

Topics: Animals; Chromatography, Thin Layer; Coronary Disease; Dogs; Female; Heart; Kinetics; Male; Myocardium; Phosphocreatine; Phospholipids

The association between phosphocreatine's antifibrillatory action and its effect on the excitement propagation processes in the ischemic area was investigated under acute coronary arterial occlusion in dogs. Ischemia considerably reduced the amplitude, and increased the duration and time of onset, in local electrograms, and provoked cardiac fibrillation at the time of occlusion or during the recovery of coronary flow. A single intravenous injection of 300 mg/kg phosphocreatine eliminated cardiac fibrillation and largely prevented electrographic changes in the ischemized area. Phosphocreatinine, phosphocreatine's structural analogue, produced a similar effect. It is suggested that antiarrhythmic action of phosphocreatine and phosphocreatinine is mediated by their membrane effects.

Topics: Acute Disease; Animals; Anti-Arrhythmia Agents; Coronary Disease; Dogs; Drug Evaluation, Preclinical; Heart Conduction System; Kinetics; Phosphocreatine; Ventricular Fibrillation

The mechanism of antiarrhythmic action of phosphocreatine on ischemic myocardium was studied by analyses of electrograms from normal and ischemic tissues. Ischemia induced significant changes in amplitude, duration, and conduction time of the electrograms, thereby showing depolarization of membranes and retarded conduction of excitation. Phosphocreatine administered in a single dose, 300 mg/kg iv, completely eliminated ventricular fibrillations in the ischemic hearts and significantly diminished the electrical instability occurring during reperfusion. The effects of phosphocreatine were completely reproduced by its structural analog phosphocreatine which is inactive in the creatine kinase reaction. It is concluded that the antiarrhythmic effect of both compounds is related to their specific chemical structure and that their specific effect is likely to be mediated via interaction with a sarcolemma site.

Topics: Animals; Anti-Arrhythmia Agents; Coronary Disease; Dogs; Electrocardiography; Phosphocreatine; Ventricular Fibrillation

The effect of phosphocreatine and phosphocreatinine on changes in crude lysophosphoglycerides (LPG) in the plasmatic membranes of canine heart, induced by short-term ischemia (an 8-minute-long occlusion of the left descending coronary artery), was examined. Ischemia caused a considerable rise in LPG level, with a mean 83% rise in lysophosphatidyl choline and a 168% rise in lysophosphatidyl ethanolamine. Intravenous administration of 300 mg/kg phosphocreatine or phosphocreatinine completely prevented the accumulation of LPG in the ischemic area. Since LPG have pronounced arrhythmogenic properties, the data obtained suggest that anti-arrhythmic activity of phosphocreatine and phosphocreatinine in acute myocardial ischemia results from the effect these substances have on membrane phospholipid metabolism in the ischemized area.

Topics: Animals; Coronary Disease; Dogs; Female; Glycerophosphates; Male; Membrane Lipids; Phosphocreatine

High-energy phosphate content and mitochondrial function were analyzed at the initiation and completion of ischemic contracture in dog hearts exposed to normothermic ischemia while on cardiopulmonary bypass. Contracture initiation and completion were detected by a balloon catheter placed within the left ventricle. In seven dogs, inner and outer layers of the myocardium were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). ATP and CP content in these two layers were compared prior to ischemia and at contracture initiation and completion. Inner layer ATP levels were 23.88 +/- 0.73 (mean +/- SM) mu moles/gm dry weight prior to ischemia, 5.14 +/- 0.49 at initiation, and 0.73 +/- 0.2 at completion. Inner layer CP content was 41.29 +/- 0.87 prior to ischemia, 3.49 +/- 0.34 at initiation, and 4.06 +/- 0.48 at completion. Mitochondrial respiratory control indices (RCI) were assayed in a second group of seven dogs prior to ischemia, at contracture initiation, and at contracture completion and were, respectively, 11.5 +/- 1.18, 3.1 +/- 0.43 and 1.76 +/- 0.29 (alpha ketoglutarate as substrate). Despite the specific degrees of metabolic deterioration associated with the events of contracture, ischemic time required to develop contracture initiation and completion was variable, ranging from 29.5 to 72 minutes for initiation and 60.25 to 101 minutes for completion. A third group of five dogs had biopsy specimens taken for ATP at fixed ischemic time intervals, and at 45 minutes of ischemia they were found to have greater ranges in ATP values than the ranges associated with contracture initiation. In contrast to ischemic time, the physiological events of ischemic contracture are reliable predictors of the degree of metabolic injury in the intact dog heart exposed to normothermic ischemic arrest during cardiopulmonary bypass.

Topics: Adenosine Triphosphate; Animals; Cardiopulmonary Bypass; Coronary Disease; Dogs; Female; Male; Mitochondria, Heart; Myocardial Contraction; Myocardium; Oxygen Consumption; Phosphocreatine; Time Factors