Pyruvate improves mitochondrial bioenergetics in an ex-vivo animal model of myocardial ischemia.

Abstract

Pyruvate is an energy substrate with known cardioprotective activity. We know now that this is due not only to its antioxidant activity, but also to its reduction of intracellular acidosis, modulation of intracytosolic calcium and improvement of cardiomyocyte contractility. However, the role of cardiac mitochondria in such positive effects has only recently begun to be understood and the exact mechanisms of the effect of pyruvate on mitochondria are still largely unknown. Aiming to study the effect of pyruvate on cardiac mitochondrial function during acute ischemia, we used an ex-vivo animal model, perfused in a Langendorff system and then subjected to ischemia in the presence and absence of pyruvate. We evaluated the mitochondrial membrane electrical potential, the respiratory chain O2 consumption (and respiratory control ratio) and the energy charges generated with different energy substrates. We conclude that pyruvate has some effect on the mitochondrial oxidative system (by non-significantly improving the respiratory control ratio), but its main action is on the phosphorylation system, significantly decreasing the time taken to complete a phosphorylation cycle (lag phase) and improving ATP production (increase in energy charge), thus allowing better maintenance of mitochondrial membrane structure, with consequent improvement of the electrical potential after a phosphorylation cycle. These findings have enabled better understanding of the mechanisms behind pyruvate cytoprotection in ischemic cardiomyopathy, clearly highlighting the essential role of cardiac mitochondria in this process.

• Authors: Pedro Monteiro, Ana Duarte, António Moreno, Lino Gonçalves, Luís A Providência
• Journal: Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology (Rev Port Cardiol) Vol. 22 Issue 1 Pg. 79-88 (Jan 2003) ISSN: 0870-2551 [Print] Portugal
• PMID: 12712812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Malates
• Glutamic Acid
• malic acid
• Pyruvic Acid
• Succinic Acid
• Oxidoreductases, N-Demethylating
• tetramethylphenylenediamine oxidase
• Ascorbic Acid

Topics

• Animals
• Ascorbic Acid (metabolism)
• Chemotherapy, Cancer, Regional Perfusion
• Female
• Glutamic Acid (metabolism)
• Intracellular Membranes (drug effects, physiology)
• Malates (metabolism)
• Male
• Membrane Potentials (drug effects)
• Mitochondria, Heart (drug effects, physiology)
• Models, Animal
• Myocardial Ischemia (chemically induced)
• Oxidoreductases, N-Demethylating (metabolism)
• Oxygen Consumption (drug effects)
• Phosphorylation (drug effects)
• Pyruvic Acid (pharmacology)
• Rats
• Rats, Wistar
• Succinic Acid (metabolism)