Effect of verapamil on baroreflex sensitivity and on cardiovascular variability.
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.
Gmitrov
J
J
Department of Physiological Hygiene, National Institute of Public Health, Tokyo, Japan.
Andrejko
S
S
D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000209:etiology / Q000401:mortality; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D011817:Rabbits; D012307:Risk Factors; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D014700:Verapamil