inosinic-acid and Myocardial-Ischemia

We tested the hypothesis that residual oxygen supply during acute low-flow ischaemia or hypoxemia is a major regulator of myocardial performance, metabolism and recovery. Rat hearts were exposed for 20 min to either ischemia (coronary flow reduced to 10% of baseline), hypoxemia (oxygen content reduced to 10% baseline) or a "mixed" condition (combined ischaemia and hypoxemia). The oxygen supply (coronary flow x oxygen content) was matched in all groups (n = 16 per group). Hypoxemic hearts had the highest performance (systolic and developed pressures, +/- dP/dtmax and oxygen uptake) and content of IMP and AMP. Ischaemic hearts had the highest content of ATP, phosphocreatine, adenine nucleotides and purines. As flow and/or oxygenation were restored, post-ischemic hearts showed better functional and metabolic recovery than post-hypoxemic ones. "Mixed" hearts were more similar to hypoxemic ones during oxygen shortage but to ischemic ones during recovery. We conclude that as oxygenation is critically limiting, coronary flow is relatively more important than oxygen supply in determining myocardial function, metabolism and recovery, most likely secondary to changes in the metabolism of diffusible substances.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Coronary Circulation; Diastole; Hypoxia; In Vitro Techniques; Inosine Monophosphate; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Oxygen Consumption; Phosphocreatine; Purines; Rats; Rats, Sprague-Dawley

The level of systemic hypoxia required to alter neonatal myocardial metabolism and its resultant effect on tolerance to global ischemia is unknown. This study examines myocardial purine nucleotides, glycogen (MG), lactate, creatine phosphate (CP) and the subsequent tolerance to ischemia in hearts exposed to varying levels of hypoxia (2 h). Three-day-old swine were randomly allocated into five study groups. Animals were anaesthetized and ventilated (2 h) with varying mixtures of medical air and nitrogen to achieve their target PaO2 (mmHg): normoxia (PaO2 = 80, n = 18), mild (PaO2 = 60, n = 10), moderate (PaO2 = 40, n = 12), moderately-severe (PaO2 = 30, n = 7) and severe (PaO2 = 20, n = 9). Arterial blood gases verified PaO2 and normal PaCO2 (39.5 +/- 0.5 mmHg). Subsequently, the heart was exposed and the metabolic profile determined from a freeze-clamp LV biopsy. The heart was excised and tolerance to ischemia determined by time (min) to ischemic contracture onset (TICo) and peak (TICp). The results demonstrated a tendency to decreased MG with progressive hypoxia which reached significance in severe hypoxia (6.6 +/- 2.7 mumol/g, P < 0.05). Despite a doubling of myocardial lactate with moderately-severe hypoxia, increases only reached significance with severe hypoxia (27.8 +/- 6.3 mumol/g, P < 0.0001). Despite the reduction in LV adenosine triphosphate (ATP) with severe hypoxia (2.16 +/- 0.68 mumol/g, P < 0.05), CP was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Animals, Newborn; Blood Gas Analysis; Glycogen; Hypoxia; Inosine Monophosphate; Lactates; Male; Myocardial Ischemia; Myocardium; Phosphocreatine; Severity of Illness Index; Swine; Time Factors

It was examined whether lactate influences postischaemic hemodynamic recovery as a function of the duration of ischaemia and whether changes in high-energy phosphate metabolism under ischaemic and reperfused conditions could be held responsible for impairment of cardiac function. To this end, isolated working rat hearts were perfused with either glucose (11 mM), glucose (11 mM) plus lactate (5 mM) or glucose (11 mM) plus pyruvate (5 mM). The extent of ischaemic injury was varied by changing the intervals of ischaemia, i.e. 15, 30 and 45 min. Perfusion by lactate evoked marked depression of functional recovery after 30 min of ischaemia. Perfusion by pyruvate resulted in marked decline of cardiac function after 45 min of ischaemia, while in glucose perfused hearts hemodynamic performance was still recovered to some extent after 45 min of ischaemia. Hence, lactate accelerates postischaemic hemodynamic impairment compared to glucose and pyruvate. The marked decline in functional recovery of the lactate perfused hearts cannot be ascribed to the extent of degradation of high-energy phosphates during ischaemia as compared to glucose and pyruvate perfused hearts. Glycolytic ATP formation (evaluated by the rate of lactate production) can neither be responsible for loss of cardiac function in the lactate perfused hearts. Moreover, failure of reenergization during reperfusion, the amount of nucleosides and oxypurines lost or the level of high-energy phosphates at the end of reperfusion cannot explain lactate-induced impairment. Alternatively, the accumulation of endogenous lactate may have contributed to ischaemic damage in the lactate perfused hearts after 30 min of ischaemia as it was higher in the lactate than in the glucose or pyruvate perfused hearts. It cannot be excluded that possible beneficial effects of the elevated glycolytic ATP formation during 15 to 30 min of ischaemia in the lactate perfused hearts are counterbalanced by the detrimental effects of lactate accumulation.

Topics: Adenosine; Adenosine Triphosphate; Animals; Energy Metabolism; Glucose; Glycogen; Guanosine Triphosphate; Heart; Hypoxanthine; Hypoxanthines; In Vitro Techniques; Inosine; Inosine Monophosphate; Kinetics; Lactates; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Phosphocreatine; Pyruvates; Rats; Rats, Inbred Lew; Time Factors; Xanthine; Xanthines