Highlights in cardiovascular effects of histamine and H-1-receptor antagonists

Despite numerous studies, the cardiac actions of histamine are still obscure. Yet, histamine could probably be clinically relevant. It is stored in large amounts in human cardiac tissue, where it is contained in the cytoplasmatic granules of mast cells (1). Mast cells are present in normal human heart tissue; they are more abundant in diseased human heart tissue where they lie in close proximity to blood vessels and between myocytes (2, 3). The histamine content of human heart mast cells is comparable to the histamine content of lung parenchymal and skin mast cells (4). Ultrastructural studies confirmed the presence of mast cells around vessels and between myocytes (2). Consequently, these cells are easily accessible to circulating antigens, drugs and stimuli that activate the cells to release vasoactive mediators which in turn can exert significant cardiovascular effects (5-7). Histamine possesses arrhythmogenic effects and once locally released, may enhance automaticity and induce triggering activity resulting in severe tachyarrhythmias. The major arrhythmogenic effects of histamine consist in increasing sinus rate and ventricular automaticity, and in slowing atrioventricular conduction (8). In addition, histamine may interfere with depolarization and repolarization through its effects on calcium and potassium currents. These effects are mediated by H2-receptor (9). Therefore direct activation of histamine receptor can induce cardiac arrhythmias. Consequently, the interference of these histaminergic effects may explain, at least in part, the arrhythmogenic effects described for some second-generation antihistamines, such as terfenadine and astemizole (10-25). In this brief review we will discuss the cardiac effects of histamine in experimental animal models and in man, and will review data on the safety of the new second-generation antihistamines, focusing on their cardiotoxic effects.