This study is the first attempt to correlate nivocardial oxygen availability by the polarographic method with direct electrocardiographic leads and cinematographic records of muscle contraction during experimental acute coronary branch occlusion and narrowing. The comparative insensitivity and slowness of the epicardial electrocardiogram as an index of acute regional ischemia is demonstrated. Special attention is given to the rates of myocardial oxygen change immediately following attainment of a significant degree of coronary obstruction, the effects of pure oxygen inhalation on the experimental situations, and alterations in coronary vein color following release of arterial occlusion. IN PREVIOUS studies 1 ' 2 it has been shown that measurements of oxygen availability by the platinum electrode provide stable values in nonischemic myocardium as well as sensitive indices of ischemia produced by coronary occlusion. The borders of ischemic areas responded to oxygen inhalation by significant rises of myocardial oxygen, whereas the centers failed to show such a response. A "physiologic" classification for ischemic muscle, based on the depth of myocardial oxygen fall, distinguished central zones (levels 25 per cent or less of the control) from border zones (levels 25 to 85 per cent of the control). This classification was roughly consistent with the anatomic extent of the ischemic area as judged from inspection. In these experiments we did not attempt to determine the rate of change in myocardial oxygen or to correlate electrocardiographs or muscle contraction changes with the polarographic findings. Supported by a grant no. 11-398 from the National Heart Institute, Xntionnl Institutes of Health, I'. S. Public Health Service.Keceived for publication .Tune 1, 19f)8.The present communication will describe the sequence of events that follow acute obstruction of a coronary branch as reflected by rapid, semicontinuous polarographic oxygen determinations, epicardial electrocardiographic records and cinematographic color records of muscle contraction. The behavior during ischemia and oxygen inhalation of each of these parameters of myocardial function will fii-st be described and commented on individually. Their interrelationships and the general implications of the experiments will then be considered. METHODSAcute regional ischemia was produced in 22 dogs weighing from 15 to 20 Kg. by an experimental teehnic previously described.1 Under morphinepentobarbital-dial-urethane anesthesia, 1 the heart wns exposed, a coronary branch isolated, and an array of oxygen electrodes inserted, so as to sample muscle within and, insofar as possible, beyond the vessel's apparent left ventricular distribution. We utilized medium-sized or small arterial branches, which in these experiments were always derivatives of the left anterior descending. We considered a small branch to be any of the terminal surface rami beyond the last major bifurcation, and a medium-sized branch to be a ranius just proximal to such a bifurcation. Larger branches we...

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...

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E HAVE previously shown that the enicardial-surface electrocardiogram is an inadequate index of localized myocardial ischemia. While striking chanares of polarographic oxygen and contractility regularly occur a few seconds after coronary arterial branch occlusion, epieardial electrocardiographic changes are delayed and sometimes absent.1 Intramyocardial electrocardiographic studies, on the other hand, reveal that localized ischemia disturbs myocardial electrical activity at least as early as either oxygenation or contractility, and over a more extensive area.We have developed a technique for amplification and recording of oxygen-reduction currents and electrocardiograms simultaneously from the same lead-point 2 "4 in the myocardium. This technique was combined with motion-picture records of muscle contraction 5 and epicardial-surface color. Thus, simultaneous information about electrical activity, oxygenation, and contractility in locally altered myocardium and adjacent, undisturbed muscle became available. This makes possible, as we will show in the present paper, an assessment of the limitations of Supported by Eesearch Grant H-398 from the National Heart Institute, National Institutes of Health, V. S. Public Health Service.Dr. Katcher is a Postdoctoral Eesearch Fellow, National Heart Institute (HF-7812 C3).Eeeeived for publication July 11, 1961. epieardial heart-body leads, which are still indispensable links between open-chest situations and the body-surface electrical phenomena of concern to the clinician. We consider such an assessment to be elementary for understanding the behavior of the heart muscle and the electrocardiogram in coronary heart disease.6 Methods In 28 dogs, weighing 15 to 23 Kg., the heart was exposed under morphine-Dial-urethane-pentobarbital anesthesia.7 A branch of the left anterior descending coronary artery was isolated. Eight to 10 glass-insulated platinum electrodes were inserted in the left ventricle as previously described. 1The construction of electrodes had been modified from those used in our earliest work. 7 The relatively heavy shank was eliminated and the entire shaft was made of light glass fused to a 0.2-mm. platinum wire which was connected at a plasticinsulated junction to a very light lead wire (no. 42 copper enameled) insulated by polyethylene tubing ( fig. 1). A white glass bead, cemented to the shaft at the level desired, acted as a depth stop and as a marker for cinematographic studies of muscle contraction. These electrodes were made the cathodes of an electrolytic circuit measuring changes in oxygen polarographically according to the method of Davies and Brink 8 and Montgomery and Horwitz. 9 The electrodes were also used as exploring lead-points for direct heart-body electrocardiograms. The platinum tips in the myocardium have an electrolytic capacitance of approximately 0.5 microfarad, which makes it possible to use them for simultaneous measurement of extracellular electrical activity. The reference electrode for both systems consisted of approximately two f...

In open-chest dogs it was found that levarterenol produced primary KS-T segment depression in epicardial surface electrocardiograms together with increases of ventricular muscle contractility. These effects occurred in nonischemic, regionally ischemic, and hypoxic myocardium and were accompanied by rises of polarographic myocardial oxygen and a reddening of coronary venous blood in all but the lowest dosages. The findings are discussed in the light of the pertinent experimental literature.