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Cardiac actions of dichloromethane in vivo correlate with depression of calcium dynamics in cultured cardiac myocytes.

Authors
Hoffmann-P; Heinroth-K; Muller-S; Buchner-E; Richards-D; Toraason-M
Source
Toxicologist 1995 Mar; 15(1):129
NIOSHTIC No.
20032245
Abstract
Previous in vitro studies with cardiac myocytes have shown that inhibition of contractility by halothane or 1,1,1-trichloroethane correlates with depression of fluctuations in cytosolic free Ca2+ concentration ([Ca2+]i). In the present study, spectrofluorometric analysis of fura-2-[Ca2+]i binding in neonatal rat cardiac myocytes revealed that cumulative exposure to 0.6-41.0 mM DCM resulted in a concentration-dependent and reversible decrease in the height of electrically induced [Ca2+]i transients. IC10 and IC50 values were 3.2 and 18.1 mM, respectively. Total inhibition of [Ca2+]i transients and cessation of beating were observed at 41.0 mM DCM. Suffusion with DCM for 40 min did not cause morphological alterations of the myocytes. In a urethane-anesthetized rat model, p.o. administration of 3.1, 6.2 or 12.4 mmol DCM/kg resulted in DCM blood concentrations of 0.98+/-0.11, 1.54+/-0.08 and 1.6+/-0.1 mM, respectively, after 15 min. A dose-dependent decrease of contractility and heart rate without influence on blood pressure and ECG parameters was observed. DCM administration also provided protection against arrhythmia development induced by CaCl2 infusion. Present data are consistent with the conclusion that cardiac effects of DCM are mediated by alterations in Ca2+ dynamics during excitation-contraction coupling.
Keywords
Animal-studies; Laboratory-animals; Myocardium; Heart; Humans; Cell-function; Cell-morphology; Exposure-assessment
CAS No.
7440-70-2; 151-67-7; 71-55-6
Publication Date
19950301
Document Type
Abstract
Fiscal Year
1995
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0731-9193
NIOSH Division
DBBS
Source Name
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland
State
OH
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