TY - JOUR
T1 - Endotoxin-induced cardiac depression is associated with decreased cardiac dihydropyridine receptors in rabbits
AU - Lew, Wilbur Y.W.
AU - Yasuda, Satoshi
AU - Yuan, Tony
AU - Hammond, H. Kirk
N1 - Funding Information:
This research was supported by the Of®ce of Research and Development, Medical Research Service of the Department of Veterans Affairs and a Grant-in-Aid from the American Heart Association (#94-703). This work was performed during the tenure of an Established Investigatorship from the American Heart Association (W.Y.W.L.), with support from the Heiwa-Nakajima Foundation and Japan Heart Foundation (S.Y.), and a NIH Short Term Training in Health Professional Schools, Grant #HL-07491 (T.Y.). The authors thank Steven Kim for his assistance with these studies.
PY - 1996/6
Y1 - 1996/6
N2 - 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.
AB - 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.
KW - Cardiac function
KW - L-type calcium channels
KW - Lipopolysaccharide
KW - Sepsis
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U2 - 10.1006/jmcc.1996.0127
DO - 10.1006/jmcc.1996.0127
M3 - Article
C2 - 8782078
AN - SCOPUS:0030002538
VL - 28
SP - 1367
EP - 1371
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 6
ER -