In experiments previously reported (1) it was found that platinum electrodes for polarographic measurement of oxygen availability have given fairly steady control readings in the left ventricular muscle of the dog. When the animals breathed pure oxygen, electrode readings rose 50-200%o. When a coronary branch was occluded they declined considerably at the borders of the ischemic area, approached zero at its center, and returned to the base line shortly after release of the ligature. If the artery was occluded with the dog breathing room air, pure oxygen breathing did not change values at the center of the ischemic area. However, it did cause a rise in the readings at the "borders" before the occlusion was released. These conclusions were based on studies of 12 anesthetized dogs using two or three electrodes simultaneously in each experiment.We have since developed a more stable dog preparation, using larger numbers of electrodes and obtaining more frequent readings which give a more complete description of the changes in local oxygen availability during short periods of coronary occlusion. Our particular concern has been to learn the size of the "border" areas that may be favorably affected by oxygen inhalation as well as the magnitude and regularity of the oxygen effect. This paper will describe the method we now use, and present a statistical analysis of the results of the first seven experiments in which we have used it. These studies would seem to have a bearing on the 1 This investigation was supported by research grants from the National Heart Institute, of the National Institutes of Health, Public Health Service (USPH-398 and 392) and from the Life Insurance Fund for Medical Research.use of oxygen inhalation for the treatment of acute myocardial infarction in man. METHODApparatus. In our earliest experiments we used the polarographic apparatus described by Montgomery and Horwitz (2) for use in the skin. Since then certain modifications have been made. We now use continuous electrolysis with six to 10 electrodes in the circuit at all times, their individual current variations being recorded when desired on a D'Arsonval galvanometer with a sensitivity of 5 X 10' amps./mm. The circuit modification is shown in Figure 1 and described in its legend. Open tip platinum electrode construction and the principles of polarography as applied to animal tissues have been described by Davies and Brink (3) and Montgomery and Horwitz (4). For the indifferent electrode we have found it necessary to immerse the dog's entire hind foot in a glass dish of saturated NaCl solution from which contact is made to the salt bridge of a calomel half cell. For electrode connections to the switch box No. 30 plain enameled wire was further insulated by placing it inside vinyl tubing. Anesthesia and gas administration. Healthy dogs weighing [15][16][17][18][19][20][21][22] Kgms. were given morphine sulfate intramuscularly (3 mg./Kgm.) followed in 45 minutes by slow intravenous injection of 0.25 cc./Kgm. of a mixture containing equal parts...
SUBSEQUENT to the observation that the intravenous infusion of fat emulsion caused a decrease in the nmyocardial oxygentension of dogs having anl experimentally produced nmyocardial infaretion, it was shown that the hyperlipemia following a large fat meal may precipitate an attack of angina pectoris in patients with severe coronary artery disease. 1-3 These attacks of angina developed about 5 hours after the fat meal, when lipeinia was near its peak. Although sublingual nitroglycerin gave subjective relief, the lipemia-induced angina could also be relieved by the intravenous injection of heparin. The plasma turbidity and triglyeeride level decreased followillg heparin, as expected, due to lipoprotein lipase activity.48 Therefore, it appeared that the level of lipemia had an effect upon the myocardium, i.e., anginal attacks developed at the time of hyperlipemia and were relieved by heparin, which induced "clearingo" of plasma. Since increasing the blood fat level in the dog decreased myoeardial oxygen tension, the present study was undertaken in order to determine whether the level of lipemia affects tissue oxygen tenision in man.The polarographic method of oxygen tension determination, which was used in the study of the dog niyocardium during fat infusion, is also a useful tool for investigation of oxygen tensioni in accessible tissue of man. It has been particularly adaptable to detern-iinations of skin oxygen tension, and thus used extensively in the study of peripheral Supported by a grant from the Lycomning County (Pennsylvania) Heart Association and the Heart Association of Southeasterni Pennsylvania.Presented in part at the Scientific Sessions of the American Heart Association, Philadelphia, Pa., October 25, 1959. Circulatzon, Volume XXII, November 1960 vascular disease. The limitations of the polaroraphic method, and the considerable information that has been obtained by its use, have been well summarized by Montgomery.9In preliminary experiments we had attempted to measure oxygen tension of the skin as lipemia developed following a fat meal. As might be expected, valid determinations of oxygen tension over the several hours of inereasing lipemia after fat ingestion were difficult to make. The polarographic method is most accurate when the subjects remain quiet, the electrode position is not disturbed, and the experiment is brief enough so that the slight downward " drift " of readings which always occurs when electrodes are in place for long periods will not hamper interpretation of data. The following procedure was therefore adopted in which oxygen tension determinations were made over reasonably brief periods during which plasma turbidity either remained at a constant level or decreased after heparin administration.
Prolonged exposure of a limb to cold water causes the disease known as immersion foot. The widespread literature has been reviewed elsewhere (1). Neuromuscular dysfunction and histopathological changes in nerve, muscle, and other tissues are readily demonstrated after such exposure. The question of how cold short of freezing damages the tissues has not been settled. Goldschmidt and Light (2) and Lewis and Love (3) suggested that the poor dissociation of oxygen from cold hemoglobin may make the tissues anoxic. It is true that the supply of oxygen by cold hemoglobin is meager (4) but it is also true that the utilization of oxygen by tissues is conspicuously lowered at such reduced temperature (5). We have demonstrated in short term experiments a reduced oxygen tension of the skin of man exposed to cold (6). The present experiments were carried out in order to learn to what extent, if any, prolonged exposure to cold lowers the oxygen tension of muscle and of the subcutaneous space, and whether oxygen inhalation will increase the oxygen tensions. Preliminary experiments on the effect of cold on the skin of human extremities were abandoned because of the danger involved. Rabbits were chosen because there has been some experience in producing immersion foot in that animal (7). Parallel studies were made of the temperatures of the muscle and of the subcutaneous tissue in order to learn the degree of chilling of tissues and in order to get some idea of the rate of blood flow through the tissues during prolonged chilling. METHODThe open tip platinum electrode (8) for estimating oxygen tension was utilized as previously described (6) except for several modifications. The electrode consists of the sharpened tip of a 0.2 mm. platinum wire, the rest of the wire electrically insulated. At voltage 0.6V. the current measured is linearly proportional to the rate of diffusion of oxygen to the electrode. For greater sensitivity to lower oxygen tension in these studies, electronic amplification was substituted for the galvanometer used in previous studies. The circuit was a modification of that used by Moody for ionization chamjer work (9).The electrodes and their wire connections were insulated to minimize electrical leakage in the special condition of underwater work. In spite of this, electrical leakage was not abolished in all experiments. When it occurred the data had to be discarded as were data from an occasional unresponsive electrode. The electrodes were placed in subcutaneous areas rather than in skin because rabbit skin is so thin as perhaps to allow its oxygen tension to be influenced by oxygen of the surrounding water and of the subcutaneous space. All data were corrected for direct temperature effect on electrical current as previously found for these electrodes (6). Measurements were made without calibrating (6) the electrodes, and the data are presented as relative (Figure 3) since the absolute values of oxygen tension are not known. We were especially interested in the changes in oxygen tension in muscle becaus...
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