Beta-adrenergic receptor blocking agents have had wide application since they were first introduced into clinical practice (Prichard et al., 1963 ;Stock, 1966), particularly in the treatment of angina pectoris (Prichard et al., 1963 ;Wolfson et al., 1966;Gillam and Prichard, 1966;Hamer and Sowton, 1966). Unfortunately these drugs have had adverse effects on myocardial function in some instances (Chamberlain, 1966;Stephen, 1966), and this may often be due to the reduction in cardiac contractile force that they are known to produce (Shanks, 1966). A drug with a similar action in angina but without the deleterious effects on myocardial function would be a most valuable addition to those currently available. I.C.I. 50172 (4-(2-hydroxy-3-isopropylaminopropoxy) acetanilide) has been shown in animal experiments to have approximately 40% of the inhibitory effect of the same dose of propranolol on isoprenaline-induced tachycardia, and mobilization of free fatty acids (Barrett et al., 1968). It has, in addition, some intrinsic sympathomimetic action not shown by propranolol (Barrett, personal communication, 1967). Its haemodynamic effects in a group of patients with ischaemic heart disease are reported here. , Materials and MethodsResults were obtained from 14 male patients whose ages ranged from 36 to 67 years (mean 54.6). Five had proved myocardial infarction from one to six days previously and were being treated in the coronary care area of the National Heart Hospital. In all these patients haemodynamic monitoring was being performed in addition to the usual electrocardiographic monitoring, to provide information of immediate therapeutic value. The drug was given only when haemodynamic values had returned to the normal range. Nine subjects had typical severe angina pectoris and were being assessed for possible surgical treatment of their coronary artery disease by internal mammary artery implants. Included in this assessment was a study of cardiac function and degree of ventricular ischaemia which involved haemodynamic measurements, and the drug was given under these circumstances.In all cases the technique of study was the same. The patients were studied in the morning after their usual breakfast and without premedication. Pulmonary artery pressure was recorded via either a fine nylon tube which was inserted percutaneously into an arm vein and guided by flow to the pulmonary artery or a No. 8 double-lumen catheter which was passed under fluoroscopic control so that the proximal lumen was in the pulmonary artery. A Teflon tube (outer diameter 1.6 mm., inner diameter 1.1 mm.) was inserted into the brachial artery percutaneously and passed to the aortic arch. Pressures were measured with Consolidated Electrodynamics straingauge transducers (type 4-326-L212) and recorded on a Sanborn (964) four-channel direct writer. Mean pressures were obtained by electrical integration. Cardiac output was measured by the dye dilution technique, 5 mg. of indocyanine green being injected into the pulmonary artery and blood withdrawn from...

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The hemodynamic effects of nitroglycerin on 20 patients with coronary arterial disease were assessed by using atrial pacing to invoke angina pectoris. This new technique also permitted study of the hemodynamics during pain without the interference of the effects of muscular exercise on the heart affected by coronary artery disease.The pain threshold of each patient was determined by successive pacing runs and the effects of nitroglycerin were evaluated both before and during the pacing up to the level of pain. With regard to the circulatory status at pain an abnormally elevated pulmonary capillary venous "wedge" pressure was an infrequent phenomenon. This difference from the data of studies in which muscular exercise is used is briefly discussed.Sublingual nitroglycerin decreased aortic, pulmonary arterial, right atrial, and pulmonary capillary venous pressures. Stroke volume and cardiac output were reduced and this reduction was accompanied by a compensatory rise in heart rate. Tension-time index was reduced and during pacing at identical rates never reached the level at which angina pectoris was experienced before nitroglycerin. End-diastolic heart size as estimated from conventional chest roentgenograms was reduced by nitroglycerin at every pacing step in all six patients studied by this method. The conclusions were that at all heart rates studied nitroglycerin (a) decreased atrial pressures, (b) decreased heart size, (c) caused peripheral vasodilatation, and (d) allowed the heart to be driven at a higher rate without production of anginal pain. These hemodynamic changes reflect a decreased oxygen requirement of the heart and are consistent with the pain-relieving properties of nitroglycerin.Additional

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