Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo

Although chronic diarrhea affects heart function and morphology, the pathog enic mechanisms are unknown. It was our hypothesis that diarrhea imposes me tabolic stress to inhibit the synthesis of new contractile proteins. To tes t this hypothesis, we investigated the effects of lactose-induced diarrhea in rats. The groups were: 1) freely fed controls, 2) rats with lactose-indu ced diarrhea or 3) pair-fed rats. After 1 wk, hearts from the rats were sub jected to subcellular fractionation techniques to isolate the major protein fractions, including myofibrillar proteins. The rates of protein synthesis were measured with concomitant assay of cardiac composition and plasma ana lytes. In comparison with the control group, diarrhea induced the following changes (P < 0.05). a decrease in heart weight, reduced RNA and mixed prot ein contents and a reduction in the fractional rate of mixed protein synthe sis. There was a reduction in the content of all protein fractions. The fra ctional synthesis rate was reduced only for the myofibrillar fraction. Plas ma insulin-like growth factor-1, but not corticosterone, was reduced. Plasm a cholesterol and triglyceride concentrations were also reduced. In compari son with the pair-fed group, diarrhea induced the following changes (P < 0. 05): a reduction in heart weight and fractional rate of mixed protein synth esis, reduced myofibrillar absolute synthesis rate and increased sarcoplasm ic/myofibrillar fractional synthesis rate ratio. Plasma bicarbonate, trigly ceride and urea concentrations were reduced, with an increase in albumin. D iarrhea impaired cardiac biochemistry, including a reduction in protein con tent and synthesis. A substantial proportion of these changes is due to ano rexia, but the selective reduction in the synthesis of contractile proteins is a feature exclusive to the diarrhea group and may be due to reductions in plasma insulin-like growth factor-1.