Oxidative Stress in Hypovolemic Shock Alters Electrical and Mechanical Activities in Isolated Rabbit Heart Papillary Muscles

Abstract

We investigated the electrophysiological and contractile responses of isolated rabbit heart papillary muscles, to plasma from the blood of rabbits suffering prolonged 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% O2 + 5% CO2) Tyrode solution at 37 °C were stimulated at a constant rate (1Hz). The action potentials (Aps) and contractions of papillary muscles were simultaneously recorded on a storage oscilloscope and photographed. SP exerted a time-dependent intense negative inotropic effect on the papillary muscles accompanied by depression of the +Vmax and prolongation of the fast and slow action potential duration in the late stages. 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 in hypovolemic shock contained humoral factors that: (a) promotes the pro duction of oxygen free radicals and NO, (b) acts an oxidative stress-induced alteration in the selectivity of the calcium channels inhibiting capacitative calcium entry or enhances endoplasmatic reticulum calcium uptake in cardiac cells, (c) effects in a direct way on voltaged gated potassium channels or indirect through the calcium activated potassium channels. The neutralisation of NO by superoxide O2-) leads to the formation of the noxious oxidant peroxynitrite (ONOO-) that may be responsible for the observed excitation-contraction uncoupling.