Adaptation of the heart to ischemia by preconditioning: Effects on energy equilibrium properties of sarcolemmal ATPases and release of cardioprotective proteins

Abstract

Ischemic preconditioning of the heart is referred as a manifest increase in tolerance of the myocardium to otherwise damaging ischemic insult, achieved by one or few consequent initial short exposures to ischemia, each followed by reperfusion of the ischemic area. Several mechanisms such as opening of collateral vessels, the action of catecholamines, inositol phosphates, G-proteins and/or adenosine; inhibition of mitochondrial ATPase, the effects of different endogenous protective substances like heat stress or shock proteins, etc., are believed to cooperate in the mechanism of induction of preconditioning or in maintaining its effect. The present study is an attempt to extend the present knowledge about preconditioning from two aspects: i.) the peculiarities of energy equilibrium in preconditioned myocardium including adaptation of cardiac sarcolemmal ATPases to ischemia and/or hypoxia, and ii) participation of a new endogenous cardioprotective substance in the mechanism of preconditioning. The energy equilibrium in preconditioning is characterized by adaptation of cardiac energy demands to the capacity of energy production and delivery decreased by anaerobiosis and is manifested by constant ratios between ATP, ADP, AMP and the sum ofADN. Principles are proposed that may enable a prediction and mathematical modelling of the balanced energetic state in the preconditioned myocardium. These principles are based on thermodynamics and involve besides others a more economic handling of ATP by sarcolemmal ATPases. The latter enzymes adapt themselves to lowered availability ofATP by decreasing besides their Vmax also their values of K_m (increase in the affinity) for ATP and some of them even adjust their activation energy (the anaerobiosis-induced elevation of E_{a t} is missing). It was also revealed that during preconditioning several up to now not described shock proteins unlike proteins (also glycoproteins) are released from the myocardium into the coronary blood. When these proteins indicated as a HS fraction were isolated, partially purified and in concentrated form applied into the coronary circulation, they were capable to induce in preliminary experiments a cardioprotective effect resembling that of the ischemic preconditioning. (Mol Cell Biochem 147: 129–137, 1995)