Author + information
- Received May 1, 1992
- Revision received September 9, 1992
- Accepted September 18, 1992
- Published online March 15, 1993.
- Kenneth M. Borow, MD, FACC∗∗,
- Alex Neumann, BS∗,
- Roberto M. Lang, MD, FACC∗,
- Donna Ehler, BS∗,
- Barbara Valentine-Bates, RN∗,
- Andrew Wolff, MD, FACC∗∗,
- Karen Friday, MD, FACC∗∗ and
- Michael Murphy, MD∗
- ↵∗Address for correspondence: Kenneth M. Borow, MD, 10 Sentry Parkway, BL 2-5, Blue Bell, Pennsylvania 19422.
Objectives. This study was designed to noninvasively assess the direct action of calcium channel blockers on left ventricular contractility in humans and to establish a framework for determining the importance of reflex sympathetic responses to any pharmacologic intervention.
Background. Assessment of left ventricular contractility in patients taking calcium channel blockers by using traditional indexes of systolic performance is difficult because of the afterload-reducing and reflex sympathetic effects of the drugs.
Methods. Fifteen hypertensive patients (mean blood pressure 127 ± 15 mm Hg) were studied with Doppler echocardiography and calibrated subclavian pulse tracings while receiving placebo and 1 week after randomization to treatment with oral nifedipine (20 mg three times daily; n = 7) or nicardipine (30 mg three times daily; n = 8). Left ventricular circumferential end-systolic wall stress versus rate-corrected velocity of shortening (Vcfc) relations were generated over a range of loads using nitroprusside. Data were acquired before and during esmolol infusion, thereby allowing assessment of hemodynamic responses with the sympathetic nervous system functionally intact as well as ablated. The adequacy of sympathetic blockade was confirmed with isoproterenol challenges. In each case, left ventricular contractile state was measured relative to placebo and esmolol data as ΔVcfcat a common end-systolic wall stress. Increased and decreased contractility were defined as ΔVcfc> 0 and ΔVcfc< 0, respectively.
Results. Nifedipne and nicardipine equally decreased blood pressure and end-systolic wall stress and increased left ventricular percent fractional shortening and stroke volume. Neither drug alone consistently altered ventricular contractility compared with placebo. Ablation of reflex sympathetic tone with esmolol unmasked a negative intropic effect for nifedipine (p = 0.03 vs. esmolol alone) but not nicardipine (p = 0.68 vs. esmolol alone). The difference between the contractility effects of nifedipine plus esmolol versus those of nicardipine plus esmolol approached statistical significance (p = 0.07).
Conclusions. Totally noninvasive techniques showed a differential effect on left ventricular contractility between nifedipine and nicardipine when alterations in afterload and reflex sympathetic responses were eliminated as confounding variables. This diagnostic approach, based on the use of pharmacologic probes, should have wide applicability for assessing the direct inotropic effect of any agent, even in the presence of complex primary and secondary physiologic modes of action.
☆ This study was supported in part by a research grant from Syntex Laboratories, Inc., Palo Alto, California and a grant-in-aid from the Chicago Heart Association, Chicago, Illinois.
- Received May 1, 1992.
- Revision received September 9, 1992.
- Accepted September 18, 1992.