Depression of contractility in cultured cardiac myocytes from neonatal rat by carbon tetrachloride and 1,1,1-trichloroethane.
The cardiac depressant effects of carbon tetrachloride (CCl(4)) and 1,1,1-trichloroethane (CH(3)CCl(3)) were evaluated in cultured heart cells from neonatal rats. Heart cells were grown on glass coverslips and formed a confluent monolayer that beat spontaneously, rhythmically and in synchrony. Contractility was assessed by video-motion analysis. Stock solutions of CCl(4) or CH(3)CCl(3) were prepared in dimethylsulphoxide (DMSO) and aliquoted (final DMSO concentration 0.2%) into medium (M199 supplemented with 5% serum) immediately prior to perfusion across myocytes in an environmentally controlled chamber. CCl(4) and CH(3)CCl(3) had a negative chronotropic effect on myocytes by prolonging the relaxation phase of beating. Duration of the contraction phase of beating, and peak velocity of cell wall movement were not affected by these halocarbons. Beating was stopped by 2.5 mm-CCl(4) or 5 mm-CH(3)CCl(3), and washout of these compounds resulted in a resumption of beating activity. Increasing (3.6 mm) or decreasing (0.6 mm) the calcium concentration of the medium (normal = 1.8 mm) significantly affected the duration of contraction and relaxation phases of beating, but did not alter the concentration-dependent action of CCl(4). A positive chronotropic effect of isoproterenol was evident from 10(-9) to 10(-6)m, but contractility was depressed by isoproterenol concentrations greater than 10(-8)m in the presence of 750 mum-CCl(4). This study demonstrates the usefulness of cultured heart cells for assessing the cardiac depressant and sensitizing actions of halogenated hydrocarbons.
Toraason
M
M
Experimental Toxicology Branch, Division of Medical and Behavioral Science, Centers for Disease Control, National Institute for Occupational Safety and Health, Robert A. Taft Laboratories, Cincinnati, OH 45226, USA.
Krueger
J A
JA
Breitenstein
M J
MJ
Swearengin
T F
TF