Effects of the Selective H1and H2Histamine Receptor Antagonists Loratadine and Ranitidine on Autonomic Control of the Heart

Abstract

Background H1 and H2 histamine receptor subtypes are present throughout the heart and may be involved in disturbances of cardiac rhythm that occur during anaphylaxis. Although H1 and H2 receptor antagonists are used in the treatment of anaphylaxis, there have been reports implicating these drugs in the genesis of dysrhythmias. This study was designed to investigate the effects of the selective H1 and H2 receptor antagonists loratadine and ranitidine on physiologic autonomic control of the healthy cardiovascular system. Methods Using a double-blind, crossover design, 14 healthy volunteers completed the protocol and were randomized to receive one dose of loratadine (20 mg), ranitidine (300 mg), or placebo on each of three separate testing sessions. Continuous electrocardiogram and BP recordings were obtained before and 3 h after administration of study drug. Effects on cardiac autonomic control were quantified using power spectral analysis of heart rate variability and calculation of spontaneous baroreflex sensitivity. Results Neither placebo nor loratadine significantly altered indices of autonomic cardiovascular control. Conversely, H2 antagonism with ranitidine resulted in a 23.3% decrease in baroreflex sensitivity (P < 0.05) and a corresponding 25.0% decrease in the ratio of high frequency to total power of heart rate variability, both indices of parasympathetic modulation (P < 0.01). Furthermore, ranitidine evoked a concomitant 103.8% increase in the ratio of low to high frequency power of heart rate variability, an index of sympathetic control (P < 0.01). Conclusions H1 receptor antagonism with loratadine does not influence physiologic cardiovascular control in young healthy subjects. However, the altered cardiac sympathovagal balance after oral administration of the H2 receptor antagonist ranitidine indicates a shift toward sympathetic predominance in heart rate control. The authors postulate that this could have implications regarding susceptibility to arrhythmias in conditions of heightened sympathetic stimulation.