CHRONIC HYPOXIA INDUCES ADAPTIVE METABOLIC CHANGES IN NEONATAL MYOCARDIUM

The effect of chronic hypoxia on neonatal myocardial metabolism remain s undefined, With a new neonatal piglet model, we determined changes i n myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days befo re they were killed. Left ventricular myocardium Has then analyzed at control and at 15-minute intervals during 60 minutes of global normoth ermic ischemia to determine high-energy phosphate levels, glycogen sto res, and lactate accumulation, Time to peak ischemic myocardial contra cture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury, Results sho wed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 mu mol/gm dry, wt. p = 0. 001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group, Initial energy ch arge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenos ine monophosphate + adenosine diphosphate + adenosine triphosphate) we re also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia, Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14. 7 mu mol/gm dry weight, p = 0.02) when compared with the control group , Lactate le, els in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 mu mol/gm dry weight, p = 0.001) compared with con trol levels and remained elevated throughout 60 minutes of ischemia, T ime to peak ischemic contracture was prolonged in the hypoxic group (6 9.5 +/- 1.8 vs 48.9 +/- 3.1 minutes, p = 0.001) compared with the cont rols group. These data show that chronic hypoxic results in significan t myocardial metabolic adaptive changes, which in turn result in an im proved tolerance to severe normothermic ischemia, These beneficial eff ects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis sis during ischemia.