Regional Distribution of Glycogen and Phosphorylase in the Ventricles of the Heart

Abstract

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

Redox State of Nicotinamide-Adenine Dinucleotide in the Inner and Outer Layers of Canine Left Ventricle, and Effects of Coronary Dilators on the Redox State

“…This view corresponds with the findings that the level of glycogen, activity of phosphorylase, and lactate/pyruvate ratio of the inner layers are higher than those of the outer in the normal heart (11,13).…”

Subendocardial Distribution of Coronary Blood Flow and the Effect of Antianginal Drugs

“…However, with reduction in total coronary blood flow produced by coronary constriction, the subendocardial layers of the stressed (36,37) and nonstressed (38) left ventricle show metabolic signs of ischemia greater than those in the epicardium, as manifested by lactate accumulation and depletion of high-energy phosphate bonds. The high glycogen content of the inner layers of the dog heart due to the subendocardial distribution of Purkinje fibers (39) should not influence the finding of normal ratios of lactate to pyruvate in these layers in hearts with adequate coronary perfusion (36,37). However, it could accentuate the lactate accumulation found in hypoxic hearts (38).…”

Transmural high energy phosphate distribution and response to alterations in workload in the normal canine myocardium as studied with spatially localized 31P NMR spectroscopy

“…In consequence, oxygen tension within the LV wall decreases progressively toward the LV chamber ( 7 , 8) and the subendocardial region becomes most susceptible to insufficiencies of O2 supply that may occur even in the normal heart at elevated heart rates and workloads. This transmural heterogeneity in O2 supply and demand, coupled with the previously documented transmural diversity in the levels of enzymes involved in ATP synthesis (8,(13)(14)(15) raise the possibility that the concentrations of substrates for the oxidative phosphosphorylation process and high energy phosphates (HEP) may also be nonuniform across the LV wall and may show transmural variation in their response to alterations in heart rate and workload. We have examined this question by measuring the myocardial HEP and "free" ADP content with transmural differentiation at different workloads and phases of the cardiac cycle using a recently developed spatially localized NMR spectroscopy technique ( 1 6 ) .…”