IN SPITE OF the widespread use of nitro-glycerin and amyl nitrite for relieving the pain of angina pectoris, considerable controversy still surrounds the mechanism of action of these two drugs. It has been proposed that they improve the relationship between coronary blood flow and the oxygen requirements of the heart by a direct dilating action on the coronary arteries, -4 or that they diminish the oxygen requirements of the myocardium by diminishing the external work of the heart.5'6 Much of the confusion concerning the actions of these drugs has arisen from the assumption that nitroglycerin and amyl nitrite have similar effects. Moreover, many studies on the peripheral circulatory effects of nitrites have been carried out with sodium nitrite, administered orally or intravenously, and it has generally been considered that the actions of this substance resemble those of nitroglycerin and of amyl nitrite. In order to determine whether the peripheral circulatory actions of nitroglycerin and amyl nitrite might play a role in their therapeutic effects, the actions of these drugs on both the resistance and capacitance vessels of the forearm of normal human subjects were determined, and the results of these studies are described in this report. The effects of nitroglycerin on ventricular dimensions are described elsewhere.7 The results of these two investigations suggest the manner in which the actions of these drugs on the peripheral circulation affect the heart, and they afford additional insight into the mechanism by which nitroglycerin and amyl nitrite provide relief of anginal pain.From the Cardiology Branch, National Heart Institute, Bethesda, Maryland.Circulation, Voluml7e XXXII, November 1965 Methods A total of 11 normal male subjects, ranging in age from 18 to 50 years, were investigated. Studies with both amyl nitrite and nitroglycerin were carried out on the forearms of nine of these subjects. All experiments were carried out with the subjects in the supine position, with the forearm elevated so that venous pressure was zero, and the possible effects of the drugs on the vessels of the hand were eliminated by inflating a wrist cuff to suprasystolic pressure levels before each measurement. A venous occlusion plethysmographic technic, employing the Whitney mercury-in-rubber strain-gauge plethysmograph,8 placed on the midforearm, was used for the measurement of forearm blood flow, as described previously.9' 10 A sphygmomanometric cuff was placed around the upper arm and venous outflow from the forearm was occluded by suddenly inflating this cuff to a pressure below the diastolic arterial pressure. Forearm blood flow was calculated from the change in forearm circumference during venous occlusion, and was expressed in ml. per 100 Gm. tissue per minute.8-10 Arterial pressure was measured through an indwelling needle placed into the brachial artery of the opposite forearm, and forearm vascular resistance was calculated as the ratio of mean arterial pressure to forearm blood flow and expressed in mm. Hg units of ml....

Although the therapeutic action of digitalis is generally agreed to result largely from its ability to stimulate the contraction of the myocardium, there has been considerable suspicion that cardiac glycosides may also act directly upon the systemic vascular bed. Excised arterial and venous strips contract when exposed to digitalis glycosides (1-4), and generalized systemic arteriolar and venous constriction has been induced by digitalis in-anesthetized open-chest dogs on cardiopulmonary bypass (5, 6). In normal human subjects digitalis glycosides elevate arterial pressure and either have little effect on or diminish cardiac output, thus augmenting the calculated systemic vascular resistance (7). More direct evidence that digitalis acts upon vascular smiiooth muscle was provided by the observation that the drug elevated systemic vascular resistance in patients on total cardiopulmonary bypass, in whom the systemic perfusion rate was held constant, and in whom the cardiac effects of the drug could not influence arterial pressure directly (8). Little information is available, however, concerning the extracardiac actions of digitalis glycosides when given in the usual clinical doses to intact human subjects. The present investigation was undertaken to characterize the effects of ouabain on a specific vascular bed, that of the forearm. The effects of the drug on both the resistance and capacitance vessels were examined in normal subjects and in patients with congestive heart failure. Materials and MethodsThe effects of ouabain were determined in 12 normal subjects, between 18 and 49 years of age, and in 6 patients with congestive heart failure, between 34 and 52 years in age. Four of these patients had rheumatic mitral

A REPORT on reactions of the fluoride ion with synthetic hydroxyapatite was presented recently.1 It was shown that with relatively pure hydroxyapatite there is a gradual change in the type of reaction as the fluoride concentration increases. With a high ratio of liquid phase to solid (10 L. of solution to 2.5 Gm. of apatite), fluorapatite is formed at the lowest concentrations of F-and gradually, as the fluoride concentration increases beyond 100 ppm, more and more of the fluoride is converted to calcium fluoride. With a low ratio of liquid to solid (100 ml. of solution and 2.5 Gm. of apatite), the formation of fluorapatite is the chief reaction up to a concentration of 0.2 per cent fluoride; beyond this point, more and more calcium fluoride is formed.Several mechanisms for the reaction of fluoride with enamel, dentin, and bone have been suggested. Neuman, Neuman, Main, O'Leary, and Smith2 have shown that fluorapatite is formed below the solubility product of calcium fluoride. Falkenheim and Hodge,' and Volker, Hodge, Wilson, and Van Voorhis4 have shown that surface adsorption of fluoride takes place. The double decomposition of apatite with high levels of fluoride has been demonstrated by Gerould,5 Scott, Picard, and Wyckoff," and others. This paper presents the results of the extension of the work on synthetic hydroxyapatite to powdered enamel and dentin and an attempt to correlate these findings with those of other workers.

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