Early studies on the heart by histological techniques, as recently reviewed by Schiebler, 1 have indicated a higher concentration of glycogen in the conduction system, than in the rest of the heart. The distribution of cardiac glycogen has been studied by chemical determination in whole atria and ventricles by Davies et al. 2 and by Weisberg and Rodbard. 3 They showed that in mammals the atria contain a higher concentration of glycogen than the ventricles.A different approach to the regional metabolism of the heart was initiated in the studies presented in this paper. An analysis of the spatial distribution of glycogen at various sites from endocardium to epicardium was made in four species of mammal. 4 In addition, the concentration of glycogen in the conduction system (A-V node and bundle of His) of heart was compared with that of the myocardium. A large diminishing gradient of glycogen concentration was observed proceeding from endocardium to epicardium of right and left ventricles. These observations led to a comparison of glycogen distribution and phosphorylase distribution, since phos-202 phorylase is one of the enzymes essential for the hydrolysis of glycogen. The finding of a concentration gradient of glycogen and phosphorylase across the cardiac walls raised the question as to whether during contraction the glycogen of a particular region is utilized preferentially over any other. To test this, contracting rabbit hearts were perfused with Feigen's solution, without glucose, and the walls were then sectioned and analyzed for glycogen content to determine glycogen disappearance. MethodsFour groups of experiments were conducted as follows: GROUP I. GLYCOGEN DISTRIBUTION IN THE LAYERS OF THE MYOCARDIUMThe opposite sides of ventricular walls of rabbit hearts were compared with respect to glycogen concentration. Rabbits were rendered unconscious by a blow on the head. In all experiments to be described, hearts were excised rapidly and plunged immediately into ice water; this produced cardiac arrest within 10 seconds of immersion. Right and left ventricles and septa were removed as rapidly as possible. In this group of experiments ventricles were divided transversely into "apex," "mid," and "base," and each section was then cut longitudinally in the center between endocardium and epicardium. All parts were weighed and glycogen concentration was determined as described below.In a more detailed study of glycogen distribution, determinations were made in hearts of nine rats, five rabbits, five dogs, and three oxen. Rats were either decapitated or, to study the effects of anesthesia on cardiac glycogen, anesthetized with ether or sodium pentobarbital (5 mg/100 g, intraperitoneally). Again rabbits were rendered

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The effects of coronary perfusion on ventricular function have been studied in isolated ventricle preparations working under different conditions. Coronary flow, oxygen consumption, ventricular stroke work, rate of ventricular pressure change during isovolumetric contraction (dPC), and diastolic ventricular pressure (DVPm) and pressure/inflow ratio were determined. Maintenance of coronary flow and oxygen consumption in 5 experiments did not prevent irreversible changes in DVPm, stroke work, and dPC when the right ventricle was acutely overloaded. These ventricles did not accumulate water. Decreasing coronary perfusion pressure at constant arterial oxygen content in 11 experiments led to inconsistent changes in DVPm, stroke work and dPC. Decreasing arterial oxygen content at constant coronary perfusion pressure in 10 experiments led to increased DVPm but inconsistent changes in stroke work and dPC. There was an inverse relationship between DVPm and oxygen consumption in the variable perfusion experiments, but not in the overloading experiments. Ventricular function did not change significantly with time in 6 experiments in which the conditions of workload and coronary perfusion were kept constant. It was concluded that irreversible changes in performance of acutely overloaded ventricles could be independent of coronary flow, myocardial water content, or duration of experiment.

Glycogen utilization in working and nonworking ventricles was studied at high (over 70 mg/100 ml) and low (27 to 61 mg/100 ml) arterial glucose concentrations and after insulin or epinephrine addition in 16 isolated ventricle preparations of dog hearts. Coronary perfusion and hemodynamic determinants of right ventricular work were controlled, and the left ventricle was kept unloaded. Time courses of change in ventricular glycogen concentration were determined during monitoring of heart rate, workload, arterial oxygen saturation, and coronary perfusion pressure. Epicardial samples for glycogen analysis were taken from each ventricle, and glucose uptake from circulating blood was determined. Glycogen loss was greater in working right than in nonworking left ventricles. In spontaneously fibrillating hearts, this difference was not observed, and there was greater glycogenolysis than during coordinated contraction. Insulin administration early in-experiments-led-to equivalent glycogen loss in working right and nonworking left ventricles. There was glycogen preservation in both ventricles of fibrillating hearts. Epinephrine augmented glycogen loss in fibrillating hearts; depletion was never complete. Myocardial glucose uptake, corrected for red cell glycolysis, was proportional to initial arterial glucose concentration. ADDITIONAL KEY WORDS myocardial glucose consumption fibrillationinsulin red cell glycolysis epinephrine • It has not yet been established whether the heart, when supplied with energy-yielding substrates in its coronary perfusate, utilizes glycogen for its energy requirements as well. We studied this question in a preparation that permitted simultaneous comparison between a working right ventricle that was pumping blood and a nonworking left ventricle that was merely contracting in the same dog heart. The metabolic pattern of glycogen was studied also in the fibrillating heart and, in another study (1), in the Langendorff preparation in which both ventricles were contracting.Glycogen concentration in each ventricle was determined in subepicardial tissue samples removed at intervals during experiments lasting 90 min. Throughout each experiment, the hearts were perfused via the coronary arteries with oxygenated whole blood or a partly synthetic medium at constant perfusion pressure, and the physiologic performance of the working right ventricle was monitored.