Sodium acetate-1-C14 was administered to anesthetized rats by continuous intravenous infusion, with simultaneous administration of d,l-α-amino-γ-phenylbutyric acid. Radioactivity measurements were made of respiratory CO2, cholesterol, fatty acids and urinary acetylamino acid. From the radioactivity data, calculations were made of rates of acetate turnover and of synthesis of cholesterol and fatty acids from acetate. Data on these metabolic functions are given for normal rats on a stock diet and for animals on a lipid-free ration. Similar experiments were carried out in rats fed thyroid powder and thiouracil. The rate of acetate turnover, and rates of synthesis of cholesterol and fatty acids from acetate, were found to be directly proportional to the basal oxygen consumption rates of the animals. The altered rates of lipid synthesis from acetate resulted, in the main, from absolute changes in rates of the reactions involved, and only to a small extent from shifts in the relative magnitudes of different pathways of acetate metabolism.
The increased physical effort necessary to breathe through a constricted orifice results in an instantaneous and uncomfortable sensation of dyspnea. The immediate sensation of difficulty in breathing is aroused by proprioceptive reflexes. The duration of inspiration and expiration becomes markedly prolonged, (1, 2) and in spite of the increased work entailed, the peak volume flow rates diminish. The minute ventilation has been shown by Cain and Otis (1) to decrease. Haldane and Priestley (3) and others (1, 4) also noted that hypoxia and retention of carbon dioxide develops due to the prolonged duration of the respiratory cycle and reduced alveolar ventilation, resulting from obstructed breathing. Furthermore, a lower or more negative intrapleural pressure develops during the inspiratory phase when breathing against a resistance. The pathological consequences of obstructed breathing, namely pulmonary congestion, have been demonstrated in animals by Moore and Binger (4, 5) and Barach and his associates (6)(7)(8).During the initial studies on the physiological effects of exsufflation, the principle of which is described in Methods, it was noted that the physical effort required to breathe against a resistance introduced at the mouth was markedly diminished (9, 10). Since exsufflation appeared subjectively to relieve dyspnea it was of interest to study its physiological effect on experimentally produced obstructed breathing in normal human subjects. METHODSTwo mechanical methods of simulating a cough in man were originally devised by Barach and his coworkers (9-11) as a means of eliminating secretions in patients who are unable to cough effectively. One of these methods, exsufflation, i.e., rapid movement of air from the lungs, is accomplished by enclosing the body of the patient in a conventional tank respirator. A negative intra-tank pressure of 40 mm. Hg, developed over a two-second period by a motor blower unit attached to the respirator, is followed by a rapid return to atmospheric pressure in 0.06 seconds by means of a swift-opening
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