Abstract

Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.

Highlights

  • Myocardial ischemia occurs when blood flow to the heart muscle is reduced by a partial or total there was a decrease of 10% to 50% of myocardial oxygen consumption, as well as a reduction of fatty acids and an increase of anaerobic glucose, glycogen depletion and lactate production

  • In this study, we demonstrate more details of metabolic changes associated to ischemia/ reperfusion injury, associating the glycogen metabolism with gluconeogenesis, aiming at a better understanding in the homeostasis of glucose metabolism during these processes

  • Such decrease in glycogen content was observed after ischemia induction at the same moment of increased pyruvate kinase transcription (Figure 3)

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Summary

Introduction

Myocardial ischemia occurs when blood flow to the heart muscle is reduced by a partial or total there was a decrease of 10% to 50% of myocardial oxygen consumption, as well as a reduction of fatty acids and an increase of anaerobic glucose, glycogen depletion and lactate production. This damage may be reversible, depending on the metabolic demands and the time of reduction of coronary flow (Ferrari et al 1998), because what determines the ischemic damage to the heart are the severity, the duration, the temporal sequence of ischemia, physical and metabolic state, myocardial glycogen content and free fatty acids (Vanoverschelde et al 1994). The reversibility of this process directly depends on the duration of ischemia and the main way to prevent this is establishing reperfusion as soon as possible (Braunwald and Kloner 1985)

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