Respiratory Chain O₂ Requirements and the Metabolic Answer to Diffuse Ischemia of Mechanically Overloaded Left Ventricular Myocardium

Abstract

Cardiac adaptation to mechanical overload proceeds in a three step manner (Meerson, 1969). After a short transitional period, a new steady state is usually attained before the heart fails. This period of enhanced metabolic activity (compensatory cardiac hypertrophy) can sometimes last over several weeks. In rats with a surgically induced aorto-caval communication (Hatt et al., 1980a), the compensated cardiac hypertrophy can persist over several months. Morphologically, the hearts from rats with a prolongated volume overload exhibit a decreased vascularization of the left ventricle (Rakusan et al., 1980). At the cellular level, the persistence of an activation of protein synthesis was suggested (Hatt et al., 1980a), the size of the left ventricular myocytes are increasing (Hatt et al., 1980b) and quantitative changes in intracellular organization appear (Anversa et al., 1971). The most striking modification is the increase in numerical density of the mitochondria resulting in an improved surface/volume ratio of mitochondria and decreased oxygen requirements for mitochondrial function (decreased cytochrome oxidase apparent K_M [O₂]; Moravec et al., 1981). In this work we tried to quantify the range of intracellular Po₂’s compatible with the unimpaired mitochondrial function (full oxidation of the cytochrome oxidase).

This work was supported by INSERM (CRL no. 81 50 44).