Circulatory depression and ventricular arrhythmias induced by compound 48/80 in anaesthetized rats.
The effects of graded doses of compound 48/80 on various cardiovascular and respiratory parameters were studied in pentobarbitone-anaesthetized rats. Following intravenous injections, this compound significantly depressed the mean blood pressure (MBP), left ventricular pressure (LVP) and dLVP/dtmax, and caused ventricular tachycardia (VT) or fibrillation (VF) and death. Heart rate (HR) response were variable, and there were no marked changes in airway resistance or blood gases. Pretreatment of the animals with either cimetidine or diphenhydramine significantly prolonged the time of onset of VT/VF but failed to alter the changes in other circulatory variables. A combination of cimetidine and diphenhydramine significantly alleviated the decreases in MBP and LVP and prevented the occurrence of VT/VF. It is suggested that the circulatory depression and the occurrence of ventricular arrhythmias following the administration of compound 48/80 result from activation of H1- and H2-receptors by elevated blood histamine levels due to release of the amine from tissues.
Dai
S
S
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000502:physiology*; D008297:Male; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology; D014693:Ventricular Fibrillation / Q000139:chemically induced; D016277:Ventricular Function, Left / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D003189:p-Methoxy-N-methylphenethylamine; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine