Direct and indirect effects of calcium entry blocking agents on isovolumic left ventricular relaxation in conscious dogs.

AUTOR(ES)

Walsh, R A

RESUMO

To assess the direct and indirect effects of the commonly used calcium entry blockers (CEB) upon the major determinants of isovolumic left ventricular relaxation, we administered equidepressant intracoronary (IC, n = 7) and equihypotensive intravenous (n = 12) dosages of diltiazem (16 +/- 3 SE micrograms/kg IC and 63 +/- 9 micrograms/kg i.v.), verapamil (10 +/- 2 and 57 +/- 5 micrograms/kg), and nifedipine (1 +/- 0.1 and 8 +/- 0.3 micrograms/kg) to preinstrumented awake dogs with normal ventricular function. The time constant of left ventricle (LV) relaxation, analyzed by two methods (T1, from the linear relation of the natural logarithm of LV pressure and time; T2, from the linear relation of LV pressure and negative high fidelity LV pressure), was significantly and equivalently prolonged by IC diltiazem (T1 + 48%, P less than 0.02), verapamil (T1 + 43%, P less than 0.001), and nifedipine (T1 + 30%, P less than 0.03). Lesser amounts of each CEB that did not affect rate of LV pressure development or extent of shortening produced no change in T1 or T2. By contrast, intravenous calcium entry blockade either produced no significant change (diltiazem and verapamil) or shortened (nifedipine T1 - 18%, P less than 0.01) LV isovolumic relaxation. However, after beta adrenergic blockade with propranolol (2 mg/kg i.v., n = 6) no change in ventricular relaxation was observed during nifedipine and the time constant was significantly prolonged by verapamil (T1 + 15%, P less than 0.05). We conclude that calcium entry blockade directly impairs normal left ventricular relaxation: This effect is closely linked to the negative inotropic properties of these drugs. The prolongation of isovolumic relaxation produced by calcium blockade is attenuated or even reversed by reflex sympathetic stimulation and favorably altered loading conditions during systemic administration.

Documentos Relacionados

• Effects of morphine on coronary and left ventricular dynamics in conscious dogs.
• Acute effects of mildly intoxicating levels of alcohol on left ventricular function in conscious dogs.
• Direct and reflex effects of nitroglycerin on coronary and left ventricular dynamics in conscious dogs
• Comparison of effects of dobutamine and ouabain on left ventricular contraction and relaxation in closed-chest dogs.
• Pharmacologic and Hemodynamic Influences on the Rate of Isovolumic Left Ventricular Relaxation in the Normal Conscious Dog