Electrophysiologic and hemodynamic actions of diltiazem: disparate temporal effects shown by experimental dose-response studies.
Diltiazem (DT), a potent slow channel blocker, has been found to be clinically useful for treatment of coronary vasospasm, hypertension, and tachyarrhythmias. Nevertheless, only limited data are available on the hemodynamic and electrophysiologic effects of DT. Atrial, His, right ventricular apex, aortic, and Swan-Ganz thermodilution catheters were used in 10 anesthetized dogs, and recordings were made during control period and after each of four infusions of DT (0.01, 0.02, 0.04, and 0.08 mg/kg/min) each lasting 30 minutes. Results showed that heart rate, pulmonary capillary wedge pressure, stroke volume, and HV interval did not change significantly. However, two dogs had second-degree AV block and a third had escape junctional rhythm during DT 0.08 mg/kg/min. Mean aortic pressure (AP), corrected sinus node (SN) recovery time, and systemic vascular resistance (SVR) were significantly reduced, whereas AH interval, AV functional and effective refractory periods were prolonged by DT. AV nodal refractory periods and AH interval were the only parameters significantly affected at DT 0.02 mg/kg/min. SN recovery time was significantly shortened at DT 0.04 mg/kg/min, whereas AP and SVR tell significantly at DT 0.08 mg/kg/min. DT had significant electrophysiologic effects at low doses, whereas hemodynamics were significantly altered only at high doses. Further, major electrophysiologic effects were on the AV node with lesser effects on SN function. Therefore, at a dose when antiarrhythmic effects are evident, the safety of diltiazem is corroborated by lack of adverse hemodynamic effects.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000097:blood / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D001552:Benzazepines; D004110:Diltiazem