Cardiorespiratory and neuroendocrine changes induced by methadone in conscious and in isoflurane anaesthetised dogs

Abstract

The aim of this study was to compare the cardiorespiratory and neurohormonal effects of methadone in conscious and in isoflurane anaesthetised dogs. Six mature dogs (28.0 +/- 3.8 kg bodyweight) received intravenous (IV) methadone (1 mg/kg) three times, once when conscious and twice during isoflurane anaesthesia (with a wash-out period of 1 week). The vasopressin antagonist relcovaptan (0.1 mg/kg IV) was administered before the methadone either during the first or second (selected randomly) isoflurane anaesthesia to evaluate the contribution of vasopressin to methadone-associated vasoconstriction. Cardiorespiratory data, plasma catecholamines and serum vasopressin were recorded before (baseline) and for 90 min after methadone.Methadone induced dysphoria in all conscious dogs and significantly (P < 0.05) increased mean arterial pressure (MAP), catecholamines, and vasopressin concentrations. During anaesthesia, in addition to significantly greater decreases in heart rate (HR) and cardiac index (Cl) than during the conscious state, methadone induced apnoea and mechanical ventilation was necessary in all dogs. In anaesthetised animals, methadone administration significantly increased vasopressin concentrations and systemic vascular resistance index (SVRI), while MAP did not differ from baseline. Relcovaptan administration did not modify the increase in SVRI associated with methadone injection during anaesthesia. Increases in plasma catecholamines may account for the slight decreases in HR and Cl seen after methadone administration in conscious dogs. In contrast, isoflurane enhanced the intensity of the cardiorespiratory changes induced by methadone. Vasoconstrictive responses associated with methadone did not appear to be induced by vasopressin.