Cardiac cachexia -pathophysiology and its mechanisms-

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1) Insulin resistance in cardiac patientsEuglycemic hyperinsulinemic glucose clamp was performed in 14 cardiovascular patients, 7 with valvular disease, 3 with arteriosclerotic disease and 4 with is ischmic heart disease and compared with nomal volunteer. Metabolic rate of insulin (MCRi) in cardiac patients were not significantly different from that of control, 464.3(]SY.+-。[)92.8vs. 419.1(]SY.+-。[)60.7ml. min. m<@D12@>D1. M value or glucose metabolized in cardiac patients was significantley lower than that of control, 5.34(]SY.+-。[)1.80 and 8.56(]SY.+-。[)0.75 mg/kg/min, respectively. Those were not dependent upon the difference in disease.2) Intracellular glucose metabolismREE of the control was 1265+127 kcal was not different from 1270+150kcal of patients. REE/BMR was correlated with M value with r=0.63 and p<0.05. Although glucose oxidation was not different, glucose storage was significant ly decreased in patient group, 2.31(]SY.+-。[)1.37 and 4.94(]SY.+-。[)0.43 mg/kg/min, respectiv … More ely. Glucose oxidation and M value were strongly correalted with r=0.88 and p<0.001.3) Glycogen contents in the myocardiumWe have established the method to measure tissue glycogen contents from a small amount of biopsied samples. In the cancer patients, glycogen contents in the skeletam muscle was positively correlated with M value obtained from clamp study, more strongly with glucose storage. In the cardiac patients, those strong correlation was not observed (currently reexamied). Energy substrates, ATP,ADP and AMP,were measured by HPLC and now under analysis.4) Relation with IL-6IL-6 in the peripheral blood was measured by ELIZA.Significant elevation of IL-6 was observed in only 2 out of 14 patients. Those were not the patients with decreased M values.5) Glucose transporters in the cardiac muscleImmunohistochmically glucose transporter4 was documented in the human cardiac muscle. We constructed primers of Glut4 and examined the presence of mRNA of Glut4 in the cardiac muscle. Recently we clearly documented the presence of Glut4 mRNA in the cardiac muscle and are now continuously investigating the quantity by competitive RT-PCR. Less