Acute Hemodynamic Effects of Medetomidine and Clonidine in Healthy Volunteers: A Noninvasive Echocardiographic Study

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Abstract
Single intravenous (i.v.) doses of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole, medetomidine (MED), (25, 50, and 100 .mu.g) and clonidine (CLO 200 .mu.g) were administered to five healthy male volunteers in a randomized, double-blind, placebo-controlled, multiple cross-over study. The hemodynamic effects of the drugs were determined by a two-dimension Doppler-echocardiographic method. Blood pressure (BP) and heart rate (HR) were monitored noninvasively. Cardiac output (CO) was maximally reduced by 23% after 100 .mu.g MED and 200 .mu.g CLO. Dose-related decreases were observed in systolic BP (SBP) and diastolic BP (DBP) and HR. Maximal reductions were 18 and 11 mm Hg and 11 beats/min after 100 .mu.g MED, and 18 and 13 mm Hg and 12 beats/min after CLO. Calculated total peripheral resistance (TPR) and the PR interval on ECG remained unchanged. Ejection fraction (EF) and stroke volume (SV) were not significantly affected by either drug, but mean circumferential fiber shortening velocity (VCF) and the preejection period/left ventricular ejection time (PEP/LVET) ratio indicated a tendency to slightly decreased myocardial performance. We conclude that the new selective .alpha.2-adrenoceptor agonist, MED, resembles CLO in its acute hemodynamic actions in healthy humans.