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Electrophysiologic assessment of calcium channel blockers in transplanted hearts: an experimental study
L Alvarez1, C Escudero, A Torralba
1Department of Experimental Surgery, Clínica Puerta de Hierro, Madrid, Spain.
Abstract:
The effects of calcium channel blockers on automaticity, conduction, and refractoriness were studied in a model of heterotopic heart transplantation in dogs, which combined an innervated heart (recipient) and a denervated one (donor). Following the surgical procedure, 0.2 mg/kg verapamil (n = 10), 0.15 mg/kg diltiazem (n = 10), or 5 microg/kg + 30 microg/kg/h nifedipine (n = 10) was administered intravenously. In basal situation and after drug administration, each heart was assessed for AV interval, cycle length, sinoatrial conduction time, atrioventricular node antegrade block point, and atrioventricular node and ventricular refractory periods; electrocardiographic PR and QT intervals and QRS complexes; systemic arterial, pulmonary artery, central venous, and pulmonary capillary wedge pressures; and cardiac output. The depressor effects of these calcium channel blockers on automaticity, refractoriness, and conduction were more intense in the transplanted hearts, very possibly because of the absence of adrenergic reflexes mediated by the autonomic nervous system; in particular, verapamil produced a great depression of sinus automaticity in a large number of cases.
Insights
Calcium channel blockers like verapamil and diltiazem more intensely affect heart function in transplanted hearts. This is likely due to the absence of autonomic nervous system reflexes in the denervated donor heart.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Electrophysiology
- Transplantation Medicine
Background:
- Calcium channel blockers are widely used for cardiovascular conditions.
- Understanding their effects on transplanted hearts is crucial for patient management.
- Autonomic nervous system influences on cardiac function are significant.
Purpose of the Study:
- To investigate the impact of calcium channel blockers on cardiac automaticity, conduction, and refractoriness.
- To compare the effects of verapamil, diltiazem, and nifedipine in a heterotopic heart transplantation model.
- To assess the role of autonomic nervous system reflexes in mediating these drug effects.
Main Methods:
- Utilized a canine heterotopic heart transplantation model combining innervated (recipient) and denervated (donor) hearts.
- Administered intravenous verapamil, diltiazem, or nifedipine.
- Assessed electrophysiological parameters (AV interval, cycle length, refractory periods), electrocardiographic intervals (PR, QT, QRS), and hemodynamic pressures and cardiac output.
Main Results:
- Calcium channel blockers exhibited more pronounced depressor effects on automaticity, refractoriness, and conduction in the transplanted (denervated) hearts compared to the innervated hearts.
- Verapamil significantly depressed sinus automaticity in a substantial number of cases.
- The heightened drug effects in transplanted hearts are possibly attributed to the absence of adrenergic reflexes.
Conclusions:
- The autonomic nervous system modulates the cardiac effects of calcium channel blockers.
- Denervated transplanted hearts are more sensitive to the electrophysiological and hemodynamic effects of calcium channel blockers.
- Clinical implications for managing heart transplant recipients on these medications should consider the absence of autonomic regulation.