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Computational Analysis of Cardiac Energetics during Ischemia and Reperfusion in Buffer‐Perfused Rabbit Hearts
Author(s) -
Wu Fan,
Vinnakota Kalyan C,
Beard Daniel A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.763.4
Subject(s) - ischemia , oxidative phosphorylation , atp hydrolysis , mitochondrion , chemistry , metabolite , perfusion , adenosine , oxygen , high energy phosphate , adenosine triphosphate , oxidative stress , adenine nucleotide , medicine , biochemistry , biophysics , atpase , nucleotide , phosphocreatine , biology , energy metabolism , enzyme , organic chemistry , gene
To determine the mechanisms by which nucleotide concentrations change in the heart during ischemia and reperfusion, data from Kroll et al. [Am. J. Physiol. 272:H2567‐2576, 1997] were analyzed using a computational model of cardiac energy metabolism and metabolite transport. In the experiments of Kroll et al., rabbit hearts were subjected to 10 minutes of perfusion at basal conditions; then 45 minutes of ischemia with 95% flow reduction; and then reperfusion. Phosphate metabolite concentrations were measured by 31 P‐Magnetic Resonance Spectroscopy ( 31 P‐MRS) and oxygen flux by arterial‐venous differences in oxygen tension during the ischemia reperfusion protocol. Data were analyzed by integrating open adenosine kinetics into a previously developed computational model [Wu et al., J. Physiol. 586:4193‐4208, 2008]. Our analyses find that during ischemia/anoxia the heart actively down‐regulates ATP hydrolysis rate in the cytoplasm, while inhibiting mitochondrial ATP consumption. Down‐regulation of mitochondria ATP consumption during anoxia may be associated with inhibition of F 1 F o ‐ATPase reversal or reduction of mitochondrial proton leak. During the reperfusion period, the mitochondrial ATP synthesis capacity is largely restored, while mitochondrial proton leak is significantly magnified resulting in a slightly impaired efficiency of mitochondrial oxidative phosphorylation. The loss of adenosine nucleotides during ischemia does not limit the mitochondrial oxidative capacity during reperfusion.