Circulatory and Respiratory Effects of Guanethidin

Guanethidin has been shown by Maxwell et al. (1959) to be a potent antihypertensive agent in dogs, and by Page and Dustan (1959) and Leishman et al. (1959) to be hypotensive in human patients.It selectively inhibits sympathetic activity, probably by blocking postganglionic adrenergic neurones.The intention of this study is to examine the acute effect of guanethidin in patients with increased pulmonary vascular resistance.Besides the possible practical implications, the subject may also be of theoretical interest as the nervous regulation of the pulmonary circulation is little known.Taylor and Donald (1960) found in hypertensive patients that bretylium tosylate, another sympathetic inhibitor, caused a rise in pulmonary vascular resistance, and they concluded that it appeared to be contra-indicated in patients with heart disease.Guanethidin, 2040 mgm.intravenously, gave in five hypertensive patients no consistent change in pulmonary artery pressures or cardiac output.Lichtlen et al. (1960) observed that 20-30 mgm.guanethidin in five hypertensive patients caused a decrease in systemic blood pressure, peripheral vascular resistance, and pulmonary artery pressure after tilting feet down, while the cardiac output was little changed.In the horizontal position the pulmonary artery pressure again rose to previous values while the cardiac output increased above the initial value, and the peripheral resistance remained low.They attribute the fall in blood pressure to a reduction of peripheral vascular resistance.Dollery et al. (1961), studying the hemodynamic response to guanethidin, noted in 7 of 11 patients a fall in blood pressure accompanied by a fall in cardiac output, when they were tilted feet down.The clinical use of adrenergic blocking agents presents many problems.Besides sudden hypo- tension, and syncope during exercise, unexplained dyspncea and severe muscular fatigue may be met with during treatment.On the other hand there are clinical reports of a beneficial effect on pulmonary cedema in hypertensive patients (Dollery et al., 1960). MATERIAL AND METHODSWe studied 22 patients during routine diagnostic heart catheterization.Seventeen had mitral stenosis, one had myxoma of the left auricle and three had pulmonary hypertension from other causes.In one patient the pressures in the pulmonary circulation were normal.There were 16 women and 6 men, aged 31 to 56 years.Two patients had a diastolic pressure above 100 mm.Hg, the others were normotensive.They were examined in the supine position before breakfast and after having taken a barbiturate, 0*l0 gm.allypropymal at least one hour previously.Pressures in the pulmonary circulation were recorded by means of an Elema strain gauge electromanometer and four-channelled direct writing electrocardiograph.The zero level was the fourth intercostal space in the anterior axillary line.A Cournand needle was placed in the femoral artery, and the cardiac output was estimated in 17 patients, using the Fick principle, after stabilization of blood pressure and 195 on August 21,