Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog.
1. The haemodynamic profile of elgodipine (1-30 micrograms kg-1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1-30 micrograms kg-1, i.v.) in chloralose-anaesthetized dogs. 2. Nicardipine produced dose-related systemic, pulmonary and coronary vasodilatation accompanied by reflex tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2). Elgodipine had similar vasodilator and hypotensive properties to nicardipine but produced less reflex inotropy, little or no reflex tachycardia and did not increase MVO2. 3. Both calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with propranolol (1 mg kg-1, i.v.) and atropine (0.3 mg kg-1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both elgodipine and nicardipine decreased heart rate and cardiac contractility and slowed atrio-ventricular conduction. Elgodipine was approximately ten times more potent than nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration. Elgodipine, unlike nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of elgodipine, which was present throughout the dose-range, appears to be largely responsible for the suppression of reflex tachycardia observed when the baroreflex is functional. 4. Elgodipine is a potent systemic and coronary vasodilator with more marked direct cardiac effects than nicardipine, particularly with respect to slowing of heart rate. The ability of elgodipine to increase coronary blood flow without significant reflex tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial oxygen supply/demand balance than nicardipine. The haemodynamic profile of elgodipine may be suitable for the treatment of angina.
Drieu la Rochelle
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CD
Department of Biology, Synthélabo Recherche, Bagneux, France.
Grosset
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A
O'Connor
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SE
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C063839:elgodipine; D001285:Atropine; D011433:Propranolol; D009529:Nicardipine