Ventricular muscle and lung protein synthesis in vivo in response to fasting, refeeding, and nutrient supply by oral and parenteral routes

Abstract

Background: Fasting and other catabolic states are characterized by reductions in the rate of protein synthesis. Most studies have investigated tissues such as skeletal muscle or liver, but impairments in the biochemistry of cardiovascular tissues also contribute to enhanced morbidity. The objectives of the present study were (1) to determine the response of protein synthesis in the heart and lung of young rats to overnight fasting; and (2) to determine whether protein synthesis could be ameliorated or modulated by refeeding or provision of enteral or parenteral nutrition.

Methods: Fractional rates of protein synthesis (ie, the percentage of tissue protein renewed each day, ks) were measured in vivo in the ventricular muscle and lungs of young male Wistar rats (body weight, 100 to 130 g) with a "flooding" dose of L-[4(3)H]phenylalanine. Rats were fed ad libitum or fasted overnight. Fasted rats were subjected to various treatments.

Results: When nutrient supply in fasted rats recommenced by refeeding for 1 hour, there were small but significant increases in the rates of ventricular protein synthesis, although the infusion of amino acids and glucose for 1 hour had no significant effect. Increases in ventricular ks were also obtained when amino acids were infused for 6 hours. Infusion of glucose alone for 6 hours did not cause a significant increase in ventricular ks. The effect of infusing a mixture of glucose plus amino acids for 6 hours was similar to the effects of amino acids alone. In all instances, ventricular ks in rats infused with amino acid for 6 hours did not attain rates observed in fed rats. ks was reduced in the lung after overnight fasting but was unresponsive to refeeding or to acute or chronic provision of amino acids and glucose by either IV or oral routes. Measurements also suggested that changes in neither insulin nor glucagon per se were responsible for the amino acid-induced increases in heart protein synthesis. However, acute treatment of rats with anti-insulin serum reduced rates of ventricular ks below values observed in fed rats. Anti-insulin serum also increased lung ks.

Conclusions: It was concluded that rates of heart protein synthesis could be increased by the chronic provision (ie, 6 hours) of nutrients by oral or IV routes. In contrast, the lung was insensitive to these treatments. The observations have important implications for clinical situations, which are characterized by diminished cardiopulmonary protein synthesis.