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Effect of verapamil on baroreflex sensitivity and on cardiovascular variability
1Department of Physiological Hygiene, National Institute of Public Health, Tokyo, Japan.
Insights
Verapamil significantly reduces baroreflex sensitivity and increases cardiovascular variability in rabbits. This effect, alongside its direct actions, may increase cardiac risk, warranting careful consideration in clinical practice.
Area of Science:
- Cardiovascular Physiology
- Autonomic Nervous System Regulation
- Pharmacology
Background:
- Depressed baroreflex sensitivity and heart rate variability are linked to reduced survival in coronary heart disease.
- Conflicting data exist regarding the impact of calcium channel antagonists on autonomic balance.
Purpose of the Study:
- To evaluate the effect of verapamil on heart rate and blood pressure variability.
- To assess verapamil's impact on baroreflex sensitivity in a rabbit model.
Main Methods:
- Baroreflex sensitivity assessed using steady-state and spectral analysis methods in sedated rabbits.
- Measurements included mean arterial blood pressure, heart rate, and microcirculation.
- Verapamil infusion (20 micrograms/kg/min) effects were measured before and after administration.
Main Results:
- Verapamil significantly reduced baroreflex sensitivity by both steady-state and transfer function methods (p < 0.001).
- Cardiovascular variability increased, indicated by elevated standard deviations in blood pressure and heart rate (p < 0.05).
- Verapamil decreased mean arterial blood pressure (-12%) and increased heart rate (+3%), with blunted blood pressure responses to phenylephrine.
Conclusions:
- Verapamil's suppressive effect on baroreflex sensitivity is significant.
- This suppression, in addition to its cardiodepressant and vasodilatory actions, may contribute to increased cardiac morbidity and mortality risk.
- Clinical consideration of verapamil's impact on baroreflex sensitivity is recommended.
Objective:
Epidemiological evidence indicates that depressed baroreflex sensitivity and heart rate variability are associated with reduced survival secondary to coronary heart disease as well as with an increased risk of developing coronary heart disease. In view of the conflicting data in the literature concerning the effect of calcium channel antagonists on autonomic balance, we evaluated the effect of verapamil on heart rate and blood pressure variability, and on baroreflex sensitivity.
Methods:
Baroreflex sensitivity was studied in 11 rabbits (27 series) under slight sedation induced by pentobarbital infusion (5 mg/kg/hour), both with a steady-state method using phenylephrine-induced blood pressure ramps, and by spectral analysis estimating the transfer function from mean arterial blood pressure to heart rate. Mean arterial blood pressure in the femoral artery, heart rate, and a microphotoelectric plethysmogram of the capillary network of rabbit's ears were simultaneously recorded during the entire experiment. Baroreflex sensitivity was measured before and after 30 min of verapamil infusion (20 micrograms/kg/min).
Results:
Verapamil-reduced baroreflex sensitivity measured by steady-state (2.6 +/- 0.2-1.7 +/- 0.2 beats/min/mmHg, mean +/- SEM) and transfer function methods (19.0 +/- 3.1-5.3 +/- 0.9; control vs. verapamil infusion, p < 0.001), and increased cardiovascular variability as estimated both by standard deviation in mean arterial blood pressure (2.0 +/- 0.1-4.0 +/- 0.4 mm Hg) and standard deviation in heart rate (6.5 +/- 1.0-9.8 +/- 1.1 bpm; p < 0.05). Verapamil increased heart rate (+3%; p < 0.05), reduced systemic mean arterial blood pressure (-12%; p < 0.05), and mean arterial blood pressure swings induced by increasing doses of phenylephrine bolus injections (-6% to -15%; p < 0.05). The reduction was larger for larger blood pressure ramps and exceeded the systemic arterial pressure reduction induced by verapamil infusion. A nonsignificant trend towards an increase in microcirculation was observed.
Conclusions:
Besides the direct cardiodepressant and vasodilatatory action of verapamil, its suppressive effect on baroreflex sensitivity should be taken into account, since this sensitivity might contribute to an increased risk of cardiac morbidity and mortality.