Effect of Tiapamil and Nifedepine During Critical Coronary Stenosis and in the Presence of Adrenergic β-Receptor Blockade in Anesthetized Dogs

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Abstract
The hemodynamic effects exerted by two chemically dissimilar calcium antagonists (tiapamil and nifedipine) were studied in anesthetized dogs during control conditions, following critical stenosis of the left circumflex coronary artery, and in the presence of beta-receptor blockade with nadolol (1 mg/kg). Dose-dependent hemodynamic changes were observed following the intravenous administration of three different doses of tiapamil (0.5, 1.0, and 2.0 mg/kg) and nifedipine (2.5, 5.0, and 10.0 micrograms/kg) during control conditions. In the presence of critical coronary stenosis, tiapamil and nifedipine produced similar magnitudes of decreases in blood pressure and changes in heart rate. Tiapamil produced paradoxic increases in left ventricular (LV) dP/dt and contractile force since these changes were accompanied by a slight decrease in heart rate. Nifedipine, unlike tiapamil, resulted in reflex increases in heart rate and myocardial contractility in response to reduction in the afterload. Also, nifedipine, unlike tiapamil, produced relatively minor changes in the coronary flow of the unoccluded left anterior descending coronary artery. In the presence of nadolol and critical stenosis, both agents produced markedly different hemodynamic responses. In the tiapamil series, three out of five dogs died due to severe cardiodepression consisting of bradycardia, hypotension, reduced myocardial contractility, and coronary blood flow. No mortality was observed in the nifedipine series since the cardiac function was adequately maintained in the presence of beta-blockade. Our results are in close agreement with the clinical observations, indicating a much higher incidence of dangerous drug interactions with combined use of verapamil-like compounds (e.g., tiapamil) with beta-blockers than with nifedipine, especially in patients with coronary artery disease and AV conduction disturbances.

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