Effect of fluid resuscitation on ryanodine receptor in macaques with endotoxic shock.

Abstract

Our recent study demonstrated that sodium bicarbonate improved cardiac function in macaque models with early-phase endotoxic shock. In the present study, we investigated further the ryanodine receptor/calcium release-channel (RyR) and calcium pump after fluid resuscitation of macaques with early-phase endotoxic shock. Twenty-four anaesthetised macaques were assigned to four groups. Nineteen animals were given an intravenous dose of 2.8 mgkg(-1) lipopolysaccharide (LPS). Sixty minutes after the LPS challenge, the animals were given (i) 5 mLkg(-1) normal saline (Ns group, n = 6), (ii) 5 mLkg(-1) of 5% sodium bicarbonate (Sb group, n = 6) or (iii) 5 mLkg(-1) of 3.5% hypertonic sodium chloride (Hs group, n = 7). The control group (Co group, n = 5) received 1 mLkg(-1) normal saline and then with 5 mLkg(-1) normal saline 60 min later. Endotoxin produced a reduction of the density of RyR but did not alter the affinity of RyR. Compared with normal saline, sodium bicarbonate or hypertonic saline induced a restoration of density of RyR but did not influence the affinity of RyR and the calcium pump. Up-regulation of RyR performance in myocardium following administration of sodium bicarbonate contributes to the improvement of cardiac function in macaques in the early phase of endotoxic shock.