Effects of Prolonged Normobaric Hypoxia and Norepinephrine on the Rat Heart—Can They Be Reversed by Normoxic Recovery?

Previous studies on rats showed a deterioration of left ventricular (LV) function and myocardial injury characterized by oxidative/nitrosative stress, PARylation, and apoptosis in the heart after three days of hypoxia. In the present study on rats, we investigated whether a three-day recovery period in normoxia can reverse myocardial injury and dysfunction. Further, we studied the effects of norepinephrine (NE) administration as a model of strong sympathetic activation on hypoxia-induced LV dysfunction and myocardial damage, as well as their reversibility. Three days of normobaric hypoxia (10% O2) significantly decreased LV systolic function. Contrary to our expectations, NE infusion even aggravated the depression in LV function. These dysfunctions were completely reversed after three days of normoxic recovery. In contrast, nitrotyrosine as a marker of oxidative/nitrosative stress receded only partially, and poly-ADP-ribose (PAR) increased even further during the recovery period. Apoptosis-inducing factor receded at least partially indicating that PAR-related apoptosis (parthanatos) is not a major cause of hypoxia-induced LV dysfunction. Additional administration of NE mildly aggravated oxidative/nitrosative stress but did not significantly intensify PARylation and consequently, parthanatos. The findings demonstrate that hypoxia-induced LV dysfunction is reversible suggesting that subchronic hypoxia and subsequent reoxygenation has a better prognosis for the LV than classical ischemia/reperfusion injury.