Cardiac muscle function during and after hypoxia: Effects of glucose concentration, mannitol and isoproterenol

Abstract

The mechanical performance of isolated rat left ventricular trabecular and papillary muscle was studied during severe hypoxia of 60 or 120 min duration and subsequent reoxygenation. Increasing substrate glucose concentration from 5.5 to 22 m m improved active tension development during the hypoxic period and after reoxygenation, and prevented the occurrence of rigor or contracture. An increase in glucose concentration 30 min after the onset of hypoxia was still effective in improving cardiac performance and recovery. The beneficial effects of glucose were not due to an osmotic mechanism, since substitution of equiosmolar mannitol for the increased glucose concentration did not improve mechanical performance. Isoproterenol (10 −5 m) addition, prior to, or during the period of hypoxia, in the presence of 5.5 m m glucose, was associated with a shortlived increase in active tension and was followed by rapid mechanical deterioration, increased contracture and poor recovery with reoxygenation. In the presence of 22m m glucose, however, isoproterenol administration led to a sustained increase in active tension without occurrence of contracture or compromise of recovery of active tension with reoxygenation. The results indicate that increased glycolytic substrate improved mechanical cardiac function during severe hypoxia and recovery therefrom. Catecholamine stimulation was deleterious to hypoxic muscle at normal circulating glucose concentrations, but with an increased level of substrate a sustained inotropic effect occurred.