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Effect on verapamil on ventricular function: studies in denervated human heart
D S Schulman1, B A Herman, T Edwards
1Department of Internal Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
Insights
Verapamil directly reduces heart contractility (inotropic effect) and heart rate (chronotropic effect) in denervated ventricles. This study clarifies verapamil
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Verapamil's effects on heart function are complex, involving direct myocardial actions, vasodilation, and sympathetic nervous system responses.
- Understanding direct myocardial effects requires isolating them from reflex sympathetic stimulation.
Purpose of the Study:
- To determine the direct impact of verapamil on human ventricular function.
- To assess verapamil's effects independent of sympathetic nervous system reflexes.
Main Methods:
- Studied 13 heart transplant recipients with denervated ventricles.
- Administered intravenous verapamil and monitored hemodynamics and radionuclide angiograms.
- Analyzed left ventricular (LV) systolic function using pressure-volume relations (SPVR) and diastolic function via peak filling rate (PFR).
Main Results:
- Verapamil decreased blood pressure and heart rate, increasing right atrial and pulmonary artery wedge pressures.
- LV ejection fraction decreased, indicating negative inotropic effects.
- No significant change in peak filling rate (PFR) was observed, suggesting minimal diastolic impact.
Conclusions:
- In denervated ventricles, verapamil exhibits direct negative chronotropic and inotropic effects.
- Verapamil has minimal direct impact on diastolic function as measured by PFR in this population.
Abstract:
Verapamil has complex influences on ventricular function owing to its direct myocardial effects, vasodilation, and reflex activation of the sympathetic nervous system. To investigate the direct myocardial effects of verapamil in humans independent of reflex sympathetic stimulation, we administered the drug to 13 recent heart transplant recipients with denervated ventricles. Hemodynamics and radionuclide angiograms were recorded at baseline, with altered loading conditions, and after intravenous (i.v.) verapamil (median dose 4 mg). Left ventricular (LV) systolic and diastolic function was analyzed by systolic pressure-volume relations (SPVR) and peak filling rate (PFR), respectively. Verapamil caused a decrease in blood pressure (BP) and heart rate (HR) with increases in right atrial pressure (RAP 6 +/- 3-8 +/- 3, p < 0.01) and pulmonary artery wedge pressure (PAWP, 9 +/- 3-11 +/- 3 mm Hg, p < 0.01) pressures. LV ejection fraction (EF) decreased (69 +/- 7-66 +/- 8%, p < 0.02) in association with an increase in LV end-systolic counts (3.45 +/- 1.27 to 4.72 +/- 1.78 kcts, p < 0.001). In 11 of 13 patients, the SPV point after verapamil administration was decreased from the line established during altered loading conditions. PFR (4.05 +/- 0.81 to 4.11 +/- 0.76 EDV/s) was unchanged. In the denervated ventricle, verapamil has negative chronotropic and inotropic effects with minimal effects on PFR.