EFFECT OF ETHANOL, HALOPERIDOL, AND LORAZEPAM ON CARDIAC CONDUCTION AND CONTRACTION

Haloperidol and lorazepam are commonly used to sedate ethanol (E)-into xicated patients in emergency departments. This study was conducted to explore the role of ethanol in altering the potency of haloperidol an d lorazepam with respect to cardiac conduction and contraction. For me chanical studies, isolated rat hearts were studied under isovolumetric conditions by using standard Langendorff technique. Hearts were perfu sed with Krebs-Heinseleit-Bicarbonate buffer containing haloperidol or lorazepam in concentrations ranging from 100 to 750 ng/ml (one heart per drug concentration). For both haloperidol and lorazepam individual ly, significant reductions in Left ventricular-generated pressure (LVG P) were observed at a concentration of 750 ng/ml (haloperidol = 2,250 nM and lorazepam = 2,000 nM). The addition of 20 and 65 mM ethanol shi fted the concentration-response effect of haloperidol such that LVGP w as significantly reduced at haloperidol = 500 and 300 ng/ml, respectiv ely (p < 0.05 vs. basal control; paired t test). Ethanol produced no o bservable shift on the lorazepam concentration-response for LVGP. For electrophysiologic studies, hearts were perfused with haloperidol and lorazepam (300 ng/ml) +/- 65 mM ethanol. Compared with basal control, E + H significantly decreased heart rate (-74 +/- 12 beats/min) and in creased His-ventricular conduction time (+7.6 +/- 1.5 ms vs. +1.7 +/- 0.6 ms for control hearts). Both haloperidol and EH significantly incr eased atrioventricular (AV) effective refractory period and the atriov entricular-His (AH) conduction interval. No significant changes in any electrophysiologic parameter were observed with ethanol or lorazepam perfused individually or with the combination of ethanol and lorazepam . Ethanol potentiates haloperidol-induced electromechanical depression of isolated rat hearts. Ethanol had no such effect on lorazepam.