Glucose uptake and amino acid metabolism in perfused hearts from tumor-bearing rats

Abstract

The purpose of this study was to evaluate whether heart glucose metabolism can account for elevated heart oxygen consumption in a tumor-bearing host. This is the first report of altered metabolism in perfused hearts from tumor-bearing animals. Glucose, glycerol, lactate, and amino acid metabolism was examined under steady-state conditions in isolated perfused hearts from sarcoma-bearing rats and compared to the metabolism in hearts from starved (96 hr) and fed control rats. Heart dry weight was reduced by 10% in tumor-bearing rats and by 30% in starved rats when compared to freely fed control animals. Cardiac glucose uptake was decreased in tumor-bearing rats (206 ± 33 μmole/hr/g dry wt) compared to both starved (298 ± 18) and fed control rats (293 ± 25). Hearts from both fed and starved controls released lactate and glycerol at significant rates during perfusion which was not evident in hearts from tumor-bearing rats. The release of individual amino acids from working hearts during perfusion was different among the animal groups with a severe depression of both glutamine and alanine release in tumor-bearing rats. In starved rats alanine release was normal although glutamine release was depressed by more than 50%. The net release of all amino acids was lowest in hearts from tumor-bearing rats, intermediate in the starved animals, and highest in the control animals, while the nonmetabolized amino acids (phenylalanine, tyrosine, methionine) were released at increased rates only from tumor-host hearts, indicating an increased net breakdown of some cardiac proteins in tumor-bearing animals. The results demonstrate that increased heart metabolism in tumor-bearing rats is associated with depressed glucose utilization. This fact suggests that oxidized free fatty acids are the preferred substrate. It is also likely that cardiac glucose metabolism does not contribute to elevated glucose and lactate turnover frequently seen in tumor-bearing hosts.