Further data are presented concerning the unusual hemodynamic effects of 1 -hiydraziniophthalazine. Previous observations demonstrating a marked increase in cardiac output in noimotensive subjects are confirmed in hypertensive patients. The splanchnic vascular bed is one of the sites of increased blood flow. The similarity between the hemodynamic effects of 1-bydr.azinophthalazine and pyirogens is pointed out and the pharmacologic basis for the clinically observed additive effects of 1-1yd)rdazinol)lpthalazine an(d hexamethonium is (liscusse(l. G ROSS and his co-workers, in animals, ' and Reubi, in man,2 were the first to demonstrate that 1-hydrazinophthalazine (Apresoline) produces a reduction of arterial pressure and simultaneously an increase in renal blood flow. Since then considerable attention has been directed toward the further elucidation of the hemodynamic effects of this agent. Moyer and his associates, working with dogs, noted a marked increase in cardiac output and decrease in total peripheral resistance following administration of 1-hydrazinophthalazine.3 This observation was confirmed in normal and hypertensive pregnant women by Assali and his co-workers using the ballistocardiographic method4 and in normal subjects by Wilkinson and his associates using the intra-

Until recently, patients with aortic insufficiency and congestive heart failure have been offered only the temporary palliation provided by rest, diet, cardiac glycosides, and diuretics. A more direct therapeutic approach would aim at correction of the basic hemodynamic defect, by mechanical reduction of the volume of regurgitation.Hufnagel (1) has devised a surgical procedure for altering the abnormal pattern of blood flow in aortic insufficiency. A plastic ball valve is inserted in the thoracic aorta, immediately distal to the left subclavian artery. This prosthesis prevents regurgitation of the blood traversing it, estimated to be approximately 75 per cent of the total cardiac output (2) (Figure 1). Blood flow above the valve, in the coronary, carotid, and subclavian systems remains regurgitant.To date, over twenty-five patients have been treated successfully in this manner (3, 4). Clinical observations suggest that patients with severe aortic insufficiency and varying degrees of cardiac decompensation benefit markedly by this operation, showing postoperatively increased exercise tolerance and clearing of the signs of heart failure. The present study was undertaken in order to demonstrate objectively the alterations in circulatory dynamics produced by the valvular prosthesis. MATERIAL AND METHODSNine patients (see Appendix) with severe aortic insufficiency as an isolated valve lesion were studied pre-

During recent years numerous investigations have been concerned with the rates of transfer or exchange of various substances across capillary beds (1-6). These studies, by analyzing curves of disappearance over several minutes from arterial plasma of intravenously injected tracer substances, have provided some information relative to all capillary beds combined. However, this type of experiment has not permitted a close analysis of the behavior of a substance during its first passage through a single organ capillary bed.Recently developed techniques (7-9) now permit the clinical investigator to examine the phenomena of transcapillary exchange of water and other diffusible substances in local vascular areas. This study was undertaken in an attempt to determine in vivo the diffusion characteristics of the pulmonary capillary bed in man with regard to deuterium oxide and an electrolyte, thiocyanate ion.Seven normal subjects and seven patients with pulmonary congestion due to heart failure were studied. The resulting data relating to the pulmonary capillaries were then compared to those previously obtained using similar tracer substances in the capillaries of the human forearm (7).

While searching for derivatives of d-tubocurarine, Barlow and Ing (1) and Paton and Zaimis (2) independently synthesized a series of polymethylene bistrimethylammonium salts. The latter investigators demonstrated that the pharmacological properties of this series were related to the length of the polymethylene chain; the decacompound produced neuromuscular block while the penta and hexa-compounds prevented the transmission of impulses across the synapses in all autonomic ganglia. They also carried out preliminary trials in man (3) but Arnold and Rosenheim were the first to use these agents in hypertension (4). Finally, Restall and Smirk demonstrated that it was possible to reduce blood pressure and obtain clinical improvement in hypertensive patients for long periods by the use of repeated parenteral doses of hexamethonium (5).Studies in this laboratory have confirmed the observations of Restall and Smirk and in addition have shown the potentiating effect of 1-hydrazinophthalazine (Apresoline) when alternated with doses of hexamethonium in patients with hypertension (6, 7). Our studies also suggested that hexamethonium may be useful in the treatment of

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