Transmural inhomogeneity of energy metabolism during acute global ischemia in the isolated rat heart: dependence on environmental conditions.

Cardiac energy metabolism is one of the earliest metabolic activities affected when either anoxia or ischemia are induced, as evidenced by the rapid decline of the tissue high-energy phosphate content of creatinephosphate (CrP) and ATP. Several reports deal with the spatial inhomogeneity of these changes and it is generally found, that the subendocardium is more sensitive to ischemia than the subepicardium. The metabolic transmural gradients observed during in vivo ischemia were attributed to both variations in wall tension and collateral flow. Lowe et al. recently presented evidence that in addition to these variations the higher vulnerability of the subendocardium to ischemia could be secondary to an increased metabolic rate.

Tissue osmolality, metabolic response, and reperfusion in myocardial ischemia.

We studied the effect of tonicity of the perfusate during reperfusion after global ischemia, in both the rat and the porcine heart. After 50 min, tissue osmolality increased by about 40 mOsm/kg. Normotonic as well as hypertonic reperfusion resulted in limited areas of "no-reflow". Metabolic restoration after reperfusion was not dependent on the tonicity of the perfusate, nor was recovery of contractility. Hypertonic reperfusion induced a higher coronary flow rate. In porcine hearts, scatter of metabolic data indicated inhomogeneity of reperfused tissue. The results differ substantially from data obtained after reperfusion of regionally ischemic hearts. Reasons for these differences are discussed.

Substrate dependence of reoxygenation arrhythmias in the isolated rat heart.

Isolated rat hearts perfused with various substrates were subjected to oxygen restriction followed by sudden reoxygenation. The incidence of ventricular arrhythmias occurring after reoxygenation appeared to be dependent on the substrate present during oxygen restriction; it was low with glucose (11 mM) and significantly higher with oleic acid (FFA to albumin molar ratio 4), with beta-hydroxy butyrate (11 mM), with acetate (11 mM) or without added substrate. When verapamil (1 muM) was also present in the medium, these arrhythmias were largely prevented. When glucose or verapamil were present during the reoxygenation period only, the incidence of reoxygenation arrhythmias was high. Tissue levels of long-chain acyl-CoA increased during oxygen restriction under all substrate conditions tested. At the moment when reoxygenation was started they were most elevated in hearts perfused with oleic acid. Verapamil did not influence levels of long-chain acyl-CoA. The amount of creatine-kinase (CK) released from the heart after reoxygenation did not correlate with the observed arrhythmias and was greatest in hearts perfused with oleic acid. Verapamil protected against CK release in the absence of added substrate, but not when oleic acid was present. It is concluded that ventricular arrhythmias after reoxygenation are not necessarily caused by FFA or long-chain acyl-CoA.