Diazepam-induced Ca2+-channel blockade reduces hypothermia-induced electromechanical changes in isolated guinea pig ventricular muscle

Abstract

Calcium-channel blockers reduce thein 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 μM nisoldipine and four were exposed to one of four diazepam concentrations (0.1, 1.0, 10 or 100 μM). A final group had no drug and provided a time-matched control. The effects were determined at 37°C and then at 27°C. At 37°C, diazepam initially increased and then reduced inotropy and APD90. Nisoldipine reduced both APD90 and inotropy. At 27°C, 100 μM diazepam and nisoldipine (1.0 μM) 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 μM) suggests that this effect has-little role in clinical use.