The effect of chronic
hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in 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 before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic
ischemia to determine high-energy
phosphate levels,
glycogen stores, and
lactate accumulation. Time to peak ischemic myocardial
contracture was measured with intramyocardial needle-tipped Millar
catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial
adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/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 charge ratios (1/2
adenosine diphosphate +
adenosine triphosphate/
adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were 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 micromol/gm dry weight, p = 0.02) when compared with the control group.
Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of
ischemia. Time to peak
ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic
hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic
ischemia. These beneficial effects are associated with elevated baseline
glycogen storage levels and an accelerated rate of anaerobic glycolysis during
ischemia.