title: Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO2 during reperfusion of ischemic hearts.
abstract: In this study we determined whether contractile function becomes uncoupled during reperfusion of ischemic hearts from mitochondrial tricarboxylic acid (TCA) cycle activity or myocardial O2 consumption (MVO2). Isolated working rat hearts perfused with buffer containing 1.2 mM palmitate and 11 mM glucose were subjected to 30 min of global ischemia followed by 60 min of aerobic reperfusion. During reperfusion, cardiac work recovered to 26.5 +/- 5.4% (n = 29) of preischemic levels, even though TCA cycle activity, fatty acid beta-oxidation, glucose oxidation, glycolysis, and MVO2 rapidly recovered. As a result, the efficiency of coupling between cardiac work and TCA cycle activity and between cardiac work and mitochondrial respiration decreased during reperfusion. In contrast, coupling of TCA cycle activity to MVO2 during reperfusion recovered to preischemic values. Addition of 1 mM dichloroacetate at reperfusion resulted in a significant increase in both cardiac work and cardiac efficiency during reperfusion. This was associated with a significant decrease in H+ production due to an improved balance between glycolysis and glucose oxidation. These data demonstrate that mitochondrial function and overall myocardial ATP production quickly recover in rat hearts after a 30-min period of global ischemia. However, mitochondrial ATP production is not efficiently translated into mechanical work during reperfusion. This may be due to an imbalance between glycolysis and glucose oxidation, resulting in an increase in H+ production and a decrease in cardiac efficiency.
authors.affiliation: Department of Pediatrics and Pharmacology, University of Alberta, Edmonton, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: el Alaoui-Talibi
authors.forename: A S
authors.initials: AS
authors.lastname: Clanachan
authors.forename: R
authors.initials: R
authors.lastname: Schulz
authors.forename: G D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002952:Citric Acid Cycle / Q000502:physiology*; D003999:Dichloroacetic Acid / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006859:Hydrogen / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011522:Protons; D006859:Hydrogen; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid; D005947:Glucose