Comparison of haemodynamic responses to cilnidipine and nicardipine in an experimental model of acute congestive heart failure.
1. The haemodynamic effects of cilnidipine, a new calcium channel blocker, were examined in a canine model of acute congestive heart failure and were compared with those of nicardipine at equihypotensive doses. 2. The model was prepared by injections of saponin into coronary arteries of anaesthetized open-chest dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF) and left ventricular dP/dt markedly decreased, while left ventricular end-diastolic pressure (LVEDP), right atrial pressure and systemic vascular resistance (SVR) increased. Cilnidipine (0.3, 1.0 and 3.0 micrograms/kg per min), nicardipine (0.3, 1.0 and 3.0 micrograms/kg per min) or the respective vehicle was given i.v. after accomplishment of heart failure. 3. These drugs both produced a comparable reduction in aortic pressure and an increase in AoF associated with profound decreases in LVEDP, SVR and coronary vascular resistance. In contrast, administration of nicardipine was associated with significant increases in heart rate and cardiac contractility but that of cilnidipine was not. 4. These results indicate that cilnidipine as well as nicardipine can exert beneficial haemodynamic effects in a model of acute heart failure probably through lessening afterload and cilnidipine may moderate reflex-induced sympathetic stimulation.
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. noguchi@med.u-ryukyu.ac.jp
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K
Noguchi
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Matsuzaki
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Koyama
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Itomine
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Sakanashi
D000208:Acute Disease; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C065927:cilnidipine; D009529:Nicardipine