Effect of ethanol, haloperidol, and lorazepam on cardiac conduction and contraction.
Haloperidol and lorazepam are commonly used to sedate ethanol (E)-intoxicated patients in emergency departments. This study was conducted to explore the role of ethanol in altering the potency of haloperidol and lorazepam with respect to cardiac conduction and contraction. For mechanical studies, isolated rat hearts were studied under isovolumetric conditions by using standard Langendorff technique. Hearts were perfused 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 individually, significant reductions in Left ventricular-generated pressure (LVGP) 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 shifted the concentration-response effect of haloperidol such that LVGP was significantly reduced at haloperidol = 500 and 300 ng/ml, respectively (p < 0.05 vs. basal control; paired t test). Ethanol produced no observable 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 increased His-ventricular conduction time (+7.6 +/- 1.5 ms vs. +1.7 +/- 0.6 ms for control hearts). Both haloperidol and EH significantly increased atrioventricular (AV) effective refractory period and the atrioventricular-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.
Medlin
R P
RP
Department of Emergency Medicine, Carolinas Medical Center, Charlotte 28232-2861, USA.
Ransom
M M
MM
Watts
J A
JA
Kline
J A
JA
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D000431:Ethanol / Q000633:toxicity*; D006220:Haloperidol / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D000431:Ethanol; D006220:Haloperidol; D008140:Lorazepam