Effects of ischaemia, blood loss and reperfusion on rat muscle protein synthesis, metabolite concentrations and polyribosome profiles in vivo

Abstract

In adult rat gastrocnemius muscles, on reperfusion after 45 min of tourniquet ischaemia, protein synthetic rates were depressed by over half for 1 h compared to normal (12%/day), and were at least one-third below normal for up to 5 h afterwards. Ischaemia caused muscle concentrations of phosphocreatine to be depressed by 70%, and those of lactate to be elevated by 350%; the proportion of ribosomes as polyribosomes was decreased by half. Unlike the rates of protein synthesis, all of these variables returned to normal after 35 min of reperfusion. When 25% of the blood volume was removed (for 10-45 min), there were falls in the rate of gastrocnemius protein synthesis and in phosphocreatine concentration, and an increase in lactate concentration. On blood replacement, protein synthesis and metabolite concentrations returned to normal within 15 min. Polyribosome profiles were unaffected by blood loss or replacement. There were highly significant correlations between the rate of gastrocnemius protein synthesis and both phosphocreatine concentration and 1/(lactate concentration), during blood loss and replacement, i.e. during both the fall and rise in muscle energy status. We conclude that the effects of ischaemia and blood loss on protein synthesis are not equivalent.

Regulation of protein turnover in skeletal and cardiac muscle

“…It is not clear whether decreases in purine nucleoside triphosphate concentrations influence protein turnover in these circumstances, although this is a strong possibility. A positive correlation between ks and PCr concentrations and an inverse correlation between k. and lactate concentrations have been detected [29,264,318]. We speculate that lactate may decrease pHi and that the changes in protein turnover and PCr concentrations result directly from this decrease (see above for a description of the effects of pH on PCr concentrations).…”

“…In vivo or in vitro, hypoxia or ischaemia decreases kRNA and kd in both heart and skeletal muscles [29,264,[315][316][317][318]. It is unclear which stage of translation is primarily affected.…”

“…In the perfused heart, ischaemia preferentially inhibits peptide-chain elongation/ termination whereas hypoxia additionally inhibits peptidechain initiation [315]. In contrast, in the hindlimb in vivo, ischaemia inhibits peptide-chain initiation [318]. It is not clear whether decreases in purine nucleoside triphosphate concentrations influence protein turnover in these circumstances, although this is a strong possibility.…”

Integrated analysis of protein and glucose metabolism during surgery: effects of anesthesia

“…It also seems possible to dismiss these changes as being the result of a contraction in the distribution space of infused leucine as a consequence of anesthesia and/or surgery-induced peripheral vasoconstriction, because surgical blood loss was minimal, patients were hemodynamically stable and well hydrated, and hypothermia as well as systemic hypoxemia were avoided throughout the study period. Because both ischemia and hypoxia have been shown to exert suppressory effects on muscle protein metabolism in animals, it is, however, a possibility that any decrease in peripheral muscle perfusion and subsequent regional depression of protein metabolism contributed to the overall effect in the whole body (29). However, a marked release of free amino acids from the leg was observed in patients undergoing cholecystectomy (28), which further emphasizes the notion that whole body protein turnover values obtained by tracer kinetics give only averages over the summation of all individual processes involved.…”

Métabolisme énergétique des muscles squelettiques chez les animaux producteurs de viande

“…Ainsi, au niveau cellulaire, une corrélation positive a été mise en évidence in vitro entre le taux de synthèse protéique et la teneur du muscle en ATP (Hedden et Buse 1982, MacLennan et Rennie 1989. Pour l'animal entier, un accroissement de l'énergie ingérée augmente davantage le taux de synthèse protéique que le taux de dégradation des protéines.…”