E. B. Chain

Abrupt reoxygenation of the anoxic potassium-arrested perfused rat heart: A study of myocardial enzyme release

Abstract Studies were undertaken, using the isolated perfused rat heart, into various aspects of anoxia-induced enzyme release from the potassium arrested myocardium. Profiles for release, over periods of up to 8 h anoxia, were obtained for protein, creatine phosphokinase, myokinase, glutamate oxaloacetate transaminase, glyceraldehyde-3-phosphate dehydrogenase and α-hydroxybutyrate dehydrogenase. Two distinct peaks of enzyme release were observed; phase 1 release, which occurred during the first 10 to 60 min of anoxia and phase 2 release which followed phase 1 release and lasted for at least 7 to 8 h. In phase 1, 2 to 5% of the enzyme was released. Reoxygenation of the heart during phase 1 had a marginal effect upon overall enzyme release. Reoxygenation during phase 2 of enzyme release resulted in an immediate and massive increase in the rate of protein and enzyme release from the myocardium.

Recovery from Cardiac Bypass and Elective Cardiac Arrest THE METABOLIC CONSEQUENCES OF VARIOUS CARDIOPLEGIC PROCEDURES IN THE ISOLATED RAT HEART

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 minutes. Various methods of arrest, either singly or in combination and with or without coronary perfusion, were studied. The functional recovery of the heart following the termination of arrest was related to the concentration of adenosine triphosphate (ATP) and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations depended on the method used to induce arrest. Normothermic ischemic arrest or electrical fibrillation led to a marked reduction in high-energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recovery. The energy status and the recovery associated with ischemic arrest were improved by combining the ischemia with potassium-induced arrest, intermittent coronary perfusion, or hypothermia. In the latter instance, a time- and temperature-dependent relationship was demonstrated. The results stress the importance of maintaining ATP and creatine phosphate levels during arrest; such maintenance requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.

REMINISCENCES OF SEVERO OCHOA FROM OUR OXFORD DAYS

Publisher Summary The first meeting between Severo and Ernst took place in the year 1933. Many of the discussions revolved around many problems concerning philosophy, human behavior, politics, art, and literature. It must be remembered that the years 1938–1940 that Severo spent at Oxford were approaching the end of the period of unsophisticated, cheap biochemistry and the beginning of the period of highly sophisticated and very expensive biochemical methodology. There were no isotopes, no chromatography, no mass spectrograph, no nuclear magnetic resonance, only the beginnings of infrared spectroscopy. Despite these methodological limitations, however, a number of important basic biochemical discoveries were made during the cheap era of biochemical research to which both Severo and Ernst were able to contribute. In the year 1940, at the beginning of the war, Spanish scientists at the Oxford decided to leave it and migrate to other countries. Severo went to the biochemistry department at St. Louis in the United States that, at that time, under Carl and Gerty Cori, was the most active laboratory in the field of carbohydrate metabolism and the study of its enzymes.