Specific Mitochondrial Adaptation to Chronic Hypoxia Counteracts Effects of Acute Hypoxia in Perfused Rats Beating Hearts

Hypoxic states of the cardiac system are associated with heart pathologies. Modifications of energetics induced by chronic hypoxia were studied under conditions of oxygen deprivation in order to understand the specific resistance encountered after adaptation to chronic hypoxia.Swiss mice were exposed to a simulated altitude of 5500m for 21 days. The effects of a low PO2 (100/120 mmHg) on contractile performance (RPP), phosphocreatine concentration (assessed by 31P‐NMR) were studied to describe the integrative changes in cardiac energetics induced by acute hypoxia from the Modular Control Analysis (MoCA).Hypoxic hearts were insensitive to the severe oxygen reduction unlike control hearts for which concomitant decreases in RPP (− 46%) and in [PCr] (−23%) were observed. This absence of change was explained by a higher sensitivity of energy supply for hypoxic hearts (p<0.01) measured under low oxygen perfusion resulting in the conservation of a healthy control pattern of contraction despite oxygen deprivation.This positive adaptation to oxygen deprivation could participate in the improvement of cardiac energetics, specifically at the level of energy supply by mitochondria. Since alteration of the energetic system could induce severe organ dysfunction, adaptation to hypoxia may limit the damages induced by acute hypoxia observed in multiple pathologies.