Adrenal medullary counterregulatory response to hypoglycemia in dogs with hepatic cross perfusion

The present study was conducted to investigate adrenal medullary responses to cross perfusion of the liver in postabsorptive anesthetized dogs. The liver of the first dog (recipient) was perfused with vena caval and aortic blood of the second dog (donor) through the portal vein and hepatic artery, respectively. Hepatic venous blood was returned to the donor through an intracaval double-lumen hepatic catheter placed in the vena cava of the recipient. A portacaval shunt was made through the right femoral vein in the recipient. Upon the cross perfusion, normoglycemic clamp in the recipient was started to compensate the loss of hepatic glucose input into the systemic circulation. When the glucose infusion was discontinued, aortic glucose level rapidly declined, within 45 min, from 125.2 ± 10.2 to 30.3 ± 4.6 mg% (p < 0.05, n = 6) along with a similarly rapid decline of aortic insulin level. Inversely, both adrenal venous epinephrine and norepinephrine increased significantly (163.2 ± 88.0 vs. 794.9 ± 55.7 ng/mL (p < 0.05) and 36.6 ± 22.4 vs. 119.7 ± 15.3 ng/mL (p < 0.05), respectively; n = 6) during this hypoglycemic period. However, in the donor, glucose level did not change either in aortic or vena caval blood, indicating that the recipient's liver was perfused with normal blood glucose levels. In the control group in which the normoglycemic clamp in the recipient was continued during the cross perfusion, both aortic glucose and adrenal venous catecholamines remained unchanged. The results indicate that the hepatic cross perfusion caused a rapid and severe hypoglycemia, resulting in a significant increase in adrenal medullary secretion, due most probably to the activation of central glucoreceptor-mediated mechanisms. This model may be useful for studying interactions between hepatic and central glucoreceptors implicated in regulatory mechanisms of glucose homeostasis.