ENDOTOXIN-INDUCED CARDIAC DEPRESSION IS ASSOCIATED WITH DECREASED CARDIAC DIHYDROPYRIDINE RECEPTORS IN RABBITS

Endotoxin depresses left ventricular (LV) contractility independently of alterations in loading conditions, acidosis, or hypoxia (Hung and L ew, 1993a). We evaluated if endotoxin-induced LV depression is associa ted with a decrease in functional L-type calcium channels, as reflecte d by the number of dihydropyridine receptors measured by [H-3]-PN200-1 10 binding. New Zealand white rabbits were instrumented with sonomicro meters to measure the end-systolic pressure-volume relationship after i.v. saline (group I, n = 6), 5 mu g/kg endotoxin (group II, n = 6), o r 10 mu g/kg endotoxin (group III, n = 6). The end-systolic volume (ES V) measured at a matched end-systolic pressure did not change signific antly over 6 h in group I (ESV changed by <5 +/- 2% S.E.) and group II (ESV changed by <3 +/- 2%), but increased markedly in group III (ESV increased 70 +/- 24%, P<0.05), indicating LV systolic depression. We m easured [H-3]-PN200-110 binding in crude membrane homogenates from the left ventricle. There was a dose-dependent decrease in B-max: 75 +/- 5 fmol/mg protein in group I, 62 +/- 3 fmol/mg in group II, and 56 +/- 5 fmol/mg in group III (P = 0.02 by ANOVA). Since the majority of dih ydropyridine receptors are functional L-type calcium channels in rabbi ts (Lew et al., 1991), we conclude that a decreased number of dihydrop yridine receptors contributes to endotoxin-induced LV depression. (C) 1996 Academic Press Limited.