D. Rourke Gilligan

Experimental studies on the effect of temporary occlusion of coronary arteries

Abstract 1. 1. Experiments were performed on thirty-nine dogs to learn whether temporary occlusion of a coronary artery would produce myocardial infarction and persistent electrocardiographic changes characteristic of myocardial ischemia. 2. 2. In twelve of eighteen animals which were allowed to survive four or more days, electrocardiographic changes typical of myocardial ischemia, and of a character not observed in control experiments, were found during the first few days to weeks after occlusion of a coronary artery for five to forty-five minutes. The type, anterior or posterior, of these electrocardiographic changes varied according to whether the anterior descending or left circumflex artery was temporarily occluded. 3. 3. Eight animals died of ventricular fibrillation during the first five minutes of occlusion of the artery, or on re-establishment of the circulation after occlusions lasting fifteen to thirty minutes. 4. 4. No gross evidences of myocardial infarction were found in the seven animals which lived for four to forty days after occlusion of a coronary artery had been maintained for five to twenty minutes. 5. 5. There were gross evidences, proved subsequently by microscopic examination, of infarction in eight of eleven experiments in which occlusion of a coronary artery was maintained for twenty-five to forty-five minutes. 6. 6. In the hearts which showed infarction, the extent of the infarct was roughly in direct proportion to the duration of the arterial occlusion; the infarcted area in several of the hearts in which an artery had been occluded for forty to forty-five minutes was as large as that which occurs after permanent and complete occlusion of the artery. 7. 7. These observations afford evidence that temporary ischemia may cause irreversible myocardial changes, and, if the ischemia be of sufficient duration, may cause myocardial infarction of the same character and degree as that which occurs after permanent and complete occlusion of an artery. 8. 8. The electrocardiographic and myocardial observations on certain patients with coronary artery disease are discussed with reference to the information gained in this study.

The Experimental Production of Intercoronary Arterial Anastomoses and their Functional Significance

Animal experiments were done to learn the degree of coronary narrowing required to produce the larger intercoronary collateral channels, their speed of development, and the degree of protection afforded the myocardium. Twelve or more days of 75 per cent narrowing were required to produce sufficiently rich anastomotic communications to protect the myocardium from damage, and to permit survival after superimposed acute complete occlusion. The physiologic and pathologic significance of the intercoronary collateral communications and the clinical implications in coronary artery disease are discussed.

STUDIES OF HEMOGLOBINEMIA AND HEMOGLOBINURIA PRODUCED IN MAN BY INTRAVENOUS INJECTION OF HEMOGLOBIN SOLUTIONS.

Hemoglobinuria is a striking feature of several hemolytic disorders, such as blackwater fever, the various paroxysmal hemoglobinurias, and certain types of acute hemolytic anemia. Available information indicates that hemoglobinuria in these conditions results from intravascular hemolysis with liberation of hemoglobin into the plasma. Quantitative studies of the plasma and urine hemoglobin and of pigments derived from hemoglobin have been made recently in this laboratory on several patients with hemoglobinuria. It was thought that comparison of the findings in normal individuals in whom hemoglobinemia and hemoglobinuria were induced by intravenous injections of hemoglobin solutions, together with the findings in clinical cases showing hemoglobinuria, might clarify certain aspects of these clinical problems. Sellards and Minot (1), Duesberg (2), and Ottenberg and Fox (3) have demonstrated that small amounts of stroma-free solutions of human hemoglobin may be injected in man without serious toxic reactions. The findings of these authors will be discussed below.

THE RATE OF ATTAINMENT OF DIFFUSION EQUILIBRIUM FOR THIOCYANATE BETWEEN PLASMA AND TRANSUDATES FOLLOWING THE INTRAVENOUS INJECTION OF SODIUM THIOCYANATE IN PATIENTS WITH EDEMA

Estimations of the volume of extracellular fluid in man have been made by calculating the volume of body fluid through which thiocyanate is distributed after the intravenous administration of sodium thiocyanate (1, 2, 3). In the method as proposed, a known amount of sodium thiocyanate in solution is administered intravenously and blood is drawn for the measurement of the concentration of thiocyanate in the serum 1 or 2 hours after the injection (1, 2). It has been demonstrated in normal man that the distribution of thiocyanate is rapid and that diffusion equilibrium is attained within 1 hour after injection (1, 2, 3). The time required for the attainment of equilibrium for CNS after intravenous injection of NaCNS in patients with edema has not been established; the present report affords information on this problem. Measurement of the CNS concentrations of serum and edema fluid has been made on samples drawn simultaneously at various times after intravenous injection of NaCNS. To establish the time required for attainment of equilibrium by analyses of transudate and serum it was necessary to know what the concentration of CNS in a transudate should be, in relation to the concentration in the serum, in a given system at equilibrium. Lavietes, Bourdillon, and Klinghoffer (2) observed in a few experiments in edematous patients that the concentration of CNS in the serum was from 5 to 21 per cent higher than in the transudate at equilibrium, when samples were drawn 12 to 64 hours after the administration of CNS. These authors suggest that CNSmay combine in some manner with protein. Studies of the protein concentrations of serum and transudate have been made in each instance in the present study, and the difference in CNS concentration between serum and transudate in each case has been analyzed in respect to the difference in protein concentration.

EXPERIENCE WITH THE HAMILTON AND HIGHMAN TEST FOR PARATHYROID HYPERFUNCTION IN CHRONIC NEPHRITIS, TOXIC GOITER, AND PAGET'S DISEASE OF BONE

In 1932 Hamilton and Schwartz (1) described a method for the detection of small amounts of parathyroid hormone, three to five units, in preparations of the hormone and in blood. In 1936 Hamilton and Highman (2) presented certain modifications of this test designed to make the method particularly applicable to the detection of abnormally large amounts of parathyroid hormone in the blood of patients suspected of having increased parathyroid function. The test consists, briefly, in measuring the increase in the serum calcium of a rabbit at definite intervals after the rabbit has received an intramuscular injection of the blood or preparation containing parathyroid hormone, the animal being given amounts of calcium chloride solution by stomach tube at definite periods during the experiment. In this communication we present our results obtained with the Hamilton and Highman test, and related blood chemical studies, in patients with chronic nephritis. The parathyroid glands of some of the patients were examined postmortem. Results obtained in toxic goiter and Pagets disease of bone are also briefly presented and discussed.

Parathyroid Function in Hyperthyroidism

Summary Studies with the Hamilton and Highman test 1 of parathyroid function have been performed in 6 patients with hyperthyroidism. The results compared with those obtained in normal subjects indicate increased circulating parathyroid hormone in the blood of 5 of the 6 thyrotoxic patients. This investigation is being continued to evaluate the significance of the findings.