Dihydroergotamine as a pharmacologic euglycemic clamp in the surgically traumatized rabbit

We assessed the utility of a pharmacologic euglycemic clamp technique by examining the metabolic and hemodynamic changes brought about by administration of dihydroergotamine (DHE) prior to anesthesia and operative trauma in the rabbit. New Zealand white rabbits received an intramuscular injection of 0.15 mg DHE/kg body weight 20 minutes before general anesthesia and minor surgical trauma, which consisted of carotid artery and jugular vein catheterizations followed by femoral artery and vein cannulations. Arterial blood was sampled every 20 minutes and assayed for glucose, lactate, nonesterified fatty acids (NEFA), and insulin. Rates of hindlimb skeletal muscle glucose uptake (Rg) and blood flow were determined 2 hours after the initial administration of DHE. DHE did not produce any effects on heart rate, blood pressure, blood flow, and Rg when compared with control animals. Liver glycogen levels were significantly higher after DHE treatment (140 +/- 31.4 v 34 +/- 9.6 mumol/g dry weight, P less than .01). Those animals receiving DHE had significantly lower and more stable plasma glucose levels than untreated animals (ranges, 5 to 9 v 7 to 22 mumol/mL plasma) and circulating NEFA were also lower and less variable (ranges, 0.1 to 1.0 v 0.1 to 2.0 muEq/mL plasma). The results show that DHE prevents stress-induced hyperglycemia in vivo in the rabbit without altering glucose uptake by skeletal muscle. The technique provides control over circulating glucose levels during the study of skeletal muscle glucose uptake without apparent negative physiologic effects.