Role of Adenosine in Acute Hibernation of Guinea-Pig Myocardium

dc.contributor.advisorH. Fred Downey
dc.contributor.committeeMemberJames L. Caffrey
dc.contributor.committeeMemberPatricia A. Gwirtz
dc.creatorGao, Zhi-Ping
dc.description.abstractGao, Zhi-Ping, Role of Adenosine in Acute Hibernation of Guinea-Pig Myocardium Doctor of Philosophy (Biomedical Sciences), August, 1995; 111 pp; 3 tables; 15 figures, bibliography, 158 titles. Myocardial hibernation is a state of depressed contractile function and energy demand during chronic ischemia. When coronary flow is restored, depressed contractile function can partially or completely recover to the pre-ischemic level, and ischemic injury of the myocardium in not evident. This project tested the hypothesis that endogenous adenosine mediates hibernation in guinea-pig myocardium. Isolated working guinea-pig hearts, perfused with glucose fortified Krebs-Henseleit buffer, were subjected to global low-flow ischemia. Left ventricular performance and cytosolic energy level were assessed. Lactate and purine nucleotides were measured in venous effluent. Heart were perfused with [U-14C]glucose to investigate the role of adenosine on glucose metabolism in myocardium. Left ventricular function in untreated hearts decreased by 80% and remained stable during ischemia, and completely recovered upon reperfusion. Neither adenosine receptor blockade with 8-p-sulfophenyl theophylline (8-SPT; 20 μM) nor ecto 5’-nucleotidase inhibitor αβ-methylene adenosine 5’-diphosphonate (AOPCP; 50μM) affected left ventricular function either ischemia or during reperfusion. Cytosolic energy level fell by 67% at 10 min ischemia in untreated hearts, but subsequently recovered to the pre-ischemic level despite continued ischemia. Adenosine receptor blockade increased cytosolic energy level at 10 min ischemia relative to untreated hearts, but blunted the subsequent rebound of phosphorylation potential. Moreover, 8-SPT doubled ischemic lactate release. Adenosine receptor blockade also increased glucose uptake during pre-ischemia and hypoperfusion, but did not stimulate glucose oxidation. Crossover plots of glycolytic intermediates revealed that phosphofructokinase, a key rate-controlling step in glycolysis, was activated by adenosine receptor blockade in both pre-ischemic and hibernating myocardium. We conclude that 1) activation of adenosine receptors results in recovery of cytosolic energy level of moderately ischemic working myocardium, but this energetic recover is not solely responsible for post-ischemic contractile recovery; 2) endogenous adenosine attenuates anaerobic glycolysis during myocardial hibernation by blunting phosphofructokinase activity.
dc.subjectAnimal Sciences
dc.subjectBehavior and Behavior Mechanisms
dc.subjectCardiovascular System
dc.subjectComparative and Laboratory Animal Medicine
dc.subjectFood Microbiology
dc.subjectLife Sciences
dc.subjectMedical Nutrition
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjectMotor Control
dc.subjectNeuroscience and Neurobiology
dc.subjectNutritional and Metabolic Diseases
dc.subjectOther Kinesiology
dc.subjectPhysiological Processes
dc.subjectSmall or Companion Animal Medicine
dc.subjectSystems and Integrative Physiology
dc.subjectSystems Biology
dc.subjectVeterinary Pathology and Pathobiology
dc.subjectVeterinary Physiology
dc.subjectacute hibernation
dc.subjectguinea pig
dc.subjectglucose metabolism
dc.subjectglucose oxidation
dc.subjectanaerobic glycolysis
dc.subjectphosphofructokinase activity
dc.titleRole of Adenosine in Acute Hibernation of Guinea-Pig Myocardium
dc.type.materialtext School of Biomedical Sciences Sciences of North Texas Health Science Center at Fort Worth of Philosophy


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