Changes of myocardial enzymes related to glycolysis and fatty acid metabolism in chronic myocardial ischemia: experiment with pigs

Abstract

To investigate the changes myocardial enzymes related to glycolysis and fatty acid metabolism in chronic myocardial ischemia and to evaluate the relationship between the gene expression of glycolytic metabolism related enzymes and myocardial viability. Fourteen Chinese experimental pigs underwent placement of arterial ring into the left anterior descending coronary artery so as to establish models of myocardial ischemia and infarction. (18)F-2-deoxy-2-fluoro-D-glucose single photon emission computed tomography was conducted to observe the viability of the myocardium. One week later the pigs were killed with their hearts taken out. Specimens of ischemic zone, infarction zone, and non-ischemic zone were obtained. RT-PCR was used to detect the mRNA expression of glucose transporter (GLUT) 1, GLUT4, medium-chain acyl-CoA dehydrogenase (MCAD), and heart-fatty acid binding protein (H-FABP). Immunohistochemistry was used to examine the protein expression of Glut1 and Glut4. Periodic Acid Schiff-hematoxylin staining was conducted to detect the glycogen. Pathological examination showed 5 pigs with myocardial infarction and 5 pigs with ischemia. In the pigs with ischemia, the mRNA expression levels of GLUT1 and GLUT4 in the ischemic zone were 9466 +/- 9033 and 60 398 +/- 64 699 respectively, both significantly higher than those in the control zone (5854 +/- 5287 and 34 188 +/- 44 714 respectively, P = 0.043, P = 0.043). the RNA expression of H-FABP in the ischemic zone was 18 123 +/- 15 925, significantly lower than that in the control zone (50 718 +/- 62 412, P = 0.043), and there was no significant difference in the mRNA expression level of MCAD. In the pigs with infarction the mRNA expression of level of H-FABP in the infarction zone was 21 919 +/- 15 224, significantly lower than that in the control zone (87 545 +/- 92 990, P = 0.043), and there were not significant differences in the mRNA expression levels of the GLUT1, GLUT4, and MCAD genes (all P > 0.05). The mRNA expression of GLUT1 in the myocardial segments with perfusion/metabolism mismatch was significantly higher than that in the myocardial segments with perfusion/metabolism match (19 794 20 454 vs 5134 + 6022, P = 0.046). The ischemic cardiac myocytes showed hypertrophy and positive staining of anti-GLUT1 polyclonal antibody. The changes of mRNA and protein expression of enzymes related to glycolysis and fatty acid metabolism after myocardial ischemia play an important role in glycolytic metabolism during myocardial ischemia.