Diazepam-induced Ca(2+)-channel blockade reduces hypothermia-induced electromechanical changes in isolated guinea pig...

Calcium-channel blockers reduce the in vitro effects of hypothermia and benzodiazepines have been reported to reduce inward calcium flow through L-type cardiac-calcium channels. Thus, this study was designed to determine if diazepam could reduce hypothermia-induced changes in ventricular papillary muscle electromechanical activity. Conventional microelectrode techniques were used while force was recorded using a miniature force transducer. Six experimental groups of electrically paced papillary muscles were formed (n = 6 per group). One was exposed to one microM nisoldipine and four were exposed to one of four diazepam concentrations (0.1, 1.0, 10 or 100 microM). A final group had no drug and provided a time-matched control. The effects were determined at 37 degrees C and then at 27 degrees C. At 37 degrees C, diazepam initially increased and then reduced inotropy and APD90. Nisoldipine reduced both APD90 and inotropy. At 27 degrees C, 100 microM diazepam and nisoldipine (1.0 microM) reduced the hypothermia-induced lengthening of APD and the increase in force. Although diazepam reduced the hypothermia-induced alterations, the concentration required to do so (100 microM) suggests that this effect has little role in clinical use.