Dipropionylcysteine ethyl ester compensates for the leakage of citric acid cycle intermediates in the pig heart with ischemia/reperfusion.

In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation assessed whether treatment with the anaplerotic medium-chain fatty acid heptanoate improves contractile function during ischemia and reperfusion. The left anterior descending coronary artery of anesthetized pigs was subjected to 60 min of 60% flow reduction and 30 min of reperfusion. Three treatment groups were studied: saline control, heptanoate (0.4 mM), or hexanoate as a negative control (0.4 mM). Treatment was initiated after 30 min of ischemia and continued through reperfusion. Myocardial CAC intermediate content was not affected by ischemia-reperfusion; however, treatment with heptanoate resulted in a more than twofold increase in fumarate and malate, with no change in citrate and succinate, while treatment with hexanoate did not increase fumarate or malate but increased succinate by 1.8-fold. There were no differences among groups in lactate exchange, glucose oxidation, oxygen consumption, and contractile power. In conclusion, despite a significant increase in the content of carbon-4 CAC intermediates, treatment with heptanoate did not result in improved mechanical function of the heart in this model of reversible ischemia-reperfusion. This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion.

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Triiodothyronine increases myocardial function and pyruvate entry into the citric acid cycle after reperfusion in a model of infant cardiopulmonary bypass

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00959.2011 ◽

2012 ◽

Vol 302 (5) ◽

pp. H1086-H1093 ◽

Cited By ~ 18

Author(s):

Aaron K. Olson ◽

Bertrand Bouchard ◽

Xue-Han Ning ◽

Nancy Isern ◽

Christine Des Rosiers ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Citric Acid ◽

Cardiac Function ◽

Citric Acid Cycle ◽

Ischemia Reperfusion ◽

Resonance Spectroscopy ◽

Acid Cycle ◽

Neonatal Piglets ◽

Group I ◽

Molar Percent

Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC), thereby providing the energy support for improved cardiac function after ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-13Carbon(13C)]pyruvate for 40 min (8 mM) during control aerobic conditions (control) or immediately after reperfusion (I/R) from global hypothermic ischemia. A third group (I/R-Tr) received T3 (1.2 μg/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-13C]pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C-nuclear magnetic resonance spectroscopy. When compared with I/R, T3 (group I/R-Tr) increased cardiac power and oxygen consumption after I/R while elevating flux of both PDC and PC (∼4-fold). Although neither I/R nor I/R-Tr modified absolute CAC levels, T3 inhibited I/R-induced reductions in their molar percent enrichment. Furthermore, 13C-labeling of CAC intermediates suggests that T3 may decrease entry of unlabeled carbons at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. T3 markedly enhances PC and PDC fluxes, thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occurs with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion.

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EFFECT OF SERUM GONADOTROPHIN ON DEHYDROGENASES OF THE CITRIC ACID CYCLE IN THE OVARY OF THE RAT

Acta Endocrinologica ◽

10.1530/acta.0.0420480 ◽

1963 ◽

Vol 42 (4) ◽

pp. 480-484 ◽

Cited By ~ 2

Author(s):

B. Eckstein ◽

R. Landsberg

Keyword(s):

Citric Acid ◽

Citric Acid Cycle ◽

Age Groups ◽

Succinic Dehydrogenase ◽

Immature Rat ◽

Acid Cycle ◽

Immature Rats ◽

Rat Ovary

ABSTRACT The succinic, malic and isocitric dehydrogenases in the ovary of immature and mature, normal and serum gonadotrophin injected rats were examined. The Qo2 of these enzymes were markedly enhanced in the gonadotrophin injected rats of both age groups, except in the case of succinic dehydrogenase in the ovary of the immature rats, where a slight non-significant decrease was noted. It is concluded that in the mature rat ovary, gonadotrophin administration stimulates the activity of all the examined dehydrogenases of the citric acid cycle, whereas in the immature rat ovary, at least the isocitric- and malic dehydrogenases are thus stimulated.

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