Metabolic disturbances during myocardial ischemia and reperfusion

Abstract

Myocardial ischemia is defined as an imbalance between fractional uptake of oxygen and the rate of cellular oxidation in the heart. This condition may have several potential outcomes: (1) when ischemia is brief, a transient post-ischemic ventricular dysfunction occurs on reperfusion, a condition termed "stunned myocardium"; (2) when it is prolonged and severe, irreversible damage occurs, with no recovery in contractile function upon reperfusion; (3) when ischemia is less severe, but still prolonged, the myocytes may remain viable but exhibit depressed contractile function. Under this condition, named "hibernating myocardium," the reperfusion is able to restore contractility. During these different ischemic conditions many biochemical changes happen; initially they represent a defensive and protective reaction against ischemic insults such as cellular acidosis and increase of inorganic phosphate levels that rapidly abolish the contractile activity. But with the prolongation of ischemia or restoration of the coronary flow, alterations in ions and overall Ca2+ homeostasis occur, together with an oxidative stress mediated by oxygen free radicals, which are not adequately counteracted by the cellular antioxidant defenses. All these biochemical alterations lead to membrane damage, mitochondrial swelling, and irreversible deterioration of contractile function.