Electrophysiological and mechanical properties of isolated rabbit heart papillary muscles and their correlation with nitric oxide (NO) and oxygen free radicals in hypovolemic shock blood plasma

Abstract

We investigated the electrophysiological and contractile responses of isolated rabbit heart papillary muscles, to plasma from the blood of rabbits suffering severe hypovolemic shock (SP) and compared the production of oxygen free radicals and nitric oxide (NO) released as a result of the hypovolemic shock. Papillary muscles removed from the right heart ventricle of 11 rabbits, superfused in an organ bath with oxygenated (95% O-2 + 5% CO2) Tyrode solution at 37 degrees C were stimulated at a constant rate (1 Hz). The action potentials (APs) and contractions of papillary muscles were simultaneously recorded on a storage oscilloscope and photographed. SP exerted an intense negative inotropic effect on the papillary muscles accompanied by depression of the +V-max and prolongation of the fast and slow action potential duration. The effects of SP were reversible, to a large extent, when the extracellular calcium concentration was increased from 1.8 to 3.6 and 5.4 mM, or after washout. The recovery was completed within 15 min. Furthermore, NO levels increased by 50 times and SP antioxidant capacity declined by 50%. These results indicate that SP contained humoral factors that promoted the production of oxygen free radicals and NO in hypovolemic shock. The neutralisation of NO by superoxide (O-2(-)) leads to the formation of the noxious oxidant peroxynitrite (ONOO-) that may be responsible for the observed excitation-contraction uncoupling.