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Respiratory control in the glucose perfused heart

作者:L. A. Katz, Alan P. Koretsky, Robert S. Balaban · 发表于:FEBS Letters · 年份:1987 · DOI:10.1016/0014-5793(87)80939-0 · 被引用次数:143 · 研究领域:Cardiovascular Function and Risk Factors、Mitochondrial Function and Pathology、Cardiac Ischemia and Reperfusion

The phosphate metabolites, adenosine diphosphate (ADP), inorganic phosphate (Pi), and adenosine triphosphate (ATP), are potentially important regulators of mitochondrial respiration in vivo. However, previous studies on the heart in vivo and in vitro have not consistently demonstrated an appropriate correlation between the concentration of these phosphate metabolites and moderate changes in work and respiration. Recently, mitochondrial NAD(P)H levels have been proposed as a potential regulator of cardiac respiration during alterations in work output. In order to understand better the mechanism of respiratory control under these conditions, we investigated the relationship between the phosphate metabolites, the NAD(P)H levels, and oxygen consumption (Q02) in the isovolumic perfused rat heart during alterations in work output with pacing. ATP, creatine phosphate (CrP), Pi and intracellular pH were measured using 31P NMR. Mitochondrial NAD(P)H levels were monitored using spectrofluorometric techniques. Utilizing glucose as the sole substrate, an increase in paced heart rate led to an increase in Q02 from 1.73 +/- 0.09 to 2.29 +/- 0.12 mmol Q2/h per g dry wt. No significant changes in the levels of Pi, PCr, ATP, or the calculated ADP levels were detected. Under identical conditions, an increase in heart rate was associated with a 23 + 3% increase in NAD(P)H fluorescence. Thus, under the conditions of these studies, an increase in Q02 was not associated with an increase in ADP or ...