Methylprednisolone and gentamicin effects on hepatosplanchnic blood flow and carbohydrate metabolism in endotoxemic Yucatan miniature pigs.
Conjoint therapy of a glucocorticoid and aminoglycoside antibiotic have been recommended for septic shock. These studies examined the hemodynamic and metabolic effects of methylprednisolone sodium succinate (MPSS) with and without gentamicin sulfate in a nonanesthetized model of nonseptic endotoxemia in Yucatan miniature pigs. Methylprednisolone sodium succinate alone had no effect on endotoxin-induced systemic hypotension. Endotoxemic pigs treated with MPSS in combination with gentamicin sulfate had lower mean arterial pressures than did MPSS-treated and nontreated endotoxemic pigs. Methylprednisolone sodium succinate alone and with gentamicin sulfate improved portal and hepatic venous blood flows moderately. Net hepatic lactate extraction, glucose production, and whole body [6-3H]glucose-derived rates of glucose appearance were also improved, but [6-3H]glucose-derived rates of glucose disappearance and blood lactate concentrations were increased, leading to no improvement in plasma glucose concentration. Pancreatic insulin secretion was higher in treated groups, which may have contributed to greater glucose utilization rates. Hepatic oxygen extraction efficiency was not affected by treatment, but increased in all groups to maintain hepatic oxygenation at base-line values. Although a calcium-antagonistic activity of gentamicin has been reported to synergize with endotoxin, thereby adversely affecting cardiovascular function, such effects did not complicate the metabolic response to steroid in the present studies.
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005839:Gentamicins / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008775:Methylprednisolone / Q000031:analogs & derivatives*; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology* / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013556:Swine, Miniature
D005839:Gentamicins; D007328:Insulin; D007773:Lactates; D008776:Methylprednisolone Hemisuccinate; D005947:Glucose; D010100:Oxygen; D008775:Methylprednisolone