Glucocorticoid effect on glycolytic intermediates in septic rat heart.

Glycolytic intermediates in rat liver show similar changes in both endotoxic and peritonitis shock models suggesting a common etiology. To determine if this parallelism exists for other organs, adult rat hearts were analyzed 5 hours after E. coli endotoxin injection (2 mg/100 gm rat weight) or after sepsis produced by cecal incision. Tissue obtained by freeze-clamp biopsy was deproteinized and the metabolites were enzymatically assayed. Glucocorticoids were injected IV: 1 mg dexamethasone sodium phosphate (DMS) and 3 mg methylprednisolone sodium succinate (MPS) per 100 gm rat weight at time of operation. Glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) in septic hearts (N = 10) declined 36% and 37% from sham-operated control values (N = 11) of 640 nmole and 136 nmole per gm wet tissue. This finding is consistent with accelerated glycolysis. No changes of other metabolites indicative of severe hypoxic conditions were noted. A 2.5-fold increase in lactate was observed. This may reflect a shift to anaerobiosis in peripheral muscle and greater extraction by heart. Confirming earlier endotoxin rat heart data, glucocorticoids did not prevent decreases in G6P and F6P in septic hearts which declined 37% and 36% below sham controls (N = 10 for pooled glucocorticoid data). Hexose monophosphates in sham animals treated with GC alone were also found to be lowered. Glucocorticoids were synergistic with endotoxin in lowering beta-hydroxybutyrate in heart samples. It is concluded that endotoxin and sepsis produce identical responses on myocardial carbohydrate metabolites and that glucocorticoids do not counter these effects, which reflects the lack of gluconeogenic potential in this organ.