Endotoxin depresses left ventricular (LV) contractility independently of alterations in loading conditions, acidosis, or hypoxia. We evaluated if endotoxin-induced LV depression is associated with a decrease in functional L-type calcium channels, as reflected by the number of dihydropyridine receptors measured by [3H]-PN200-110 binding. New Zealand white rabbits were instrumented with sonomicrometers to measure the end-systolic pressure-volume relationship after i.v. saline (group I, n = 6), 5 μg/kg endotoxin (group II, n = 6), or 10 μg/kg endotoxin (group III, n = 6). The end-systolic volume (ESV) measured at a matched end-systolic pressure did not change significantly over 6 h in group [(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 measured [3H]-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 dihydropyridine receptors are functional L-type calcium channels in rabbits, we conclude that a decreased number of dihydropyridine receptors contributes to endotoxin-induced LV depression.
- Cardiac function
- L-type calcium channels
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine