Minoxidil: right atrial cardiac pathology in animals and in man.

tion of several methods for computing stroke volume from central aortic pressure. Catheter-flush system for continuous monitoring of central arterial pulse wave form. Characteristics of aortic diastolic pressure decay with application to the continuous monitoring of changes in peripheral vascular resistance. SUMMARY Minoxidil is a clinically effective vasodilator with a low order of toxicity, except for a canine-specific lesion of the right atrium of the heart of dogs after they are given daily doses of 1 mg/kg or greater for 30 days. In these experiments the canine right atrial lesion was generally located adjacent to the second of the three atrial branches of the right coronary artery and had grossly red or yellowish thickening of the atrial wall. Microscopically there was extravasation of a few intact red cells, atrophy of myocardial cells adjacent to the subepicardium, the presence of mast cells and macrophages containing hemosiderin with subsequent proliferation of angioblasts and connective tissue cells. Cytoplasmic loss in myocardial cells of the left ventricular papillary muscle identical in all respects to that seen after other hypotensive agents and fi-adrenoceptor agonists was also observed in minoxidil-treated rodents and dogs. Seventy-nine of 158 patients who died secondary to severe hypertension but who received minoxidil were autopsied. Six cases had significant right atrial pathology not related to gross and histologic changes found in the right atrial lesions of dogs. A prospective study of the right atrium of normotensive and hypertensive patients not treated with minoxidil shows an increasing frequency of histologic changes, such as myocardial fibrosis and hydropic vacuolization that are related to age and the presence of hypertension. MINOXIDIL (Loniten, Upjohn) is a chemically unique (fig. 1), orally active vasodilator drug that profoundly and consistently reduces mean blood pressure in rats, miniature pigs, rhesus monkeys, nor-motensive mongrel and beagle and hypertensive mongrel dogs.' Several clinical trials have reconfirmed its efficacy;2 3 a controlled trial by Dargie et al.4 showed that minoxidil, in combination with pro-pranolol and diuretics, lowers the blood pressure of hypertensive patients resistant to treatment with large doses of standard antihypertensive drugs. The therapeutic importance of chronically administered minoxidil in man stimulated comprehensive toxicologic studies. In general, the drug has little toxicity when given intraperitoneally or orally and causes minimal pharmacologic effects except in the-cardiovascular system. The drug does produce hir-sutism in humans, an annoying side effect, especially in women. Teratology studies in pregnant rats and rabbits were negative. Daily doses …