Non invasive study of systemic and regional haemodynamic and cardiac effects of a new calcium antagonist, SR 33557, in healthy volunteers.
The systemic and regional haemodynamic and cardiac effects of two oral doses (100 and 300 mg) of a new sulphone-indolizine calcium antagonist SR 33,557 (SR) and a placebo were non invasively investigated in a double-blind, cross-over study in 6 healthy male volunteers. Arterial pressure, heart rate, cardiac output, brachial and carotid artery diameters and flows and PR and QT intervals were studied. Stroke volume, total peripheral and forearm vascular resistance, regional cardiac output distribution indices and corrected QT intervals were calculated. SR did not produce any significant modification in systemic haemodynamics, although arterial pressure and cardiac output tended to decrease slightly after 300 mg. In contrast, at the regional level, ST produced strong vasodilatation and significantly increased brachial and carotid blood flow. SR-induced vasodilation affected only the arterioles, as shown by a significant decrease in forearm vascular resistance, but not the large arteries, as shown by lack of change in the brachial and carotid artery diameters. SR-induced vasodilation preferentially affected the brachial rather than the carotid vascular bed, resulting in a redistribution of cardiac output towards the musculo-cutaneous territories. SR caused a marked and long-lasting decrease in heart rate, but it did not affect the auriculo-ventricular conduction time.
Bellissant
E
E
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin, France.
Thuillez
C
C
Kechrid
R
R
Duhaze
P
P
Giudicelli
J F
JF
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D004311:Double-Blind Method; D015150:Echocardiography, Doppler / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007212:Indolizines / Q000494:pharmacology*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D007212:Indolizines; D010627:Phenethylamines; C059901:fantofarone