Cerebral blood flow and metabolism in dogs with chronic diabetes

Previously, the authors found that anesthetized diabetic dogs had increased cerebral blood flow (CBF) and oxygen consumption (CMRO2). These results may have been influenced by anesthesia or surgery. The aim of this study was to determine whether CBF and CMRO2 are increased in the awake or anesthetized state in the absence of acute surgical stress in diabetic dogs. A second aim was to determine whether increased CBF and CMRO2 in diabetic dogs are mediated through beta-adrenergic mechanisms. Diabetic dogs (n = 8) underwent total surgical pancreatectomy followed by 4 months of insulin management (16 +/- 0.4 units/day, mean +/- SE) to maintain fasting and 3 PM blood glucose 10-17 mM. Control dogs (n = 8) underwent sham operation followed by a 4-month convalescence. Using previously inserted catheters, CBF (radiolabelled microspheres) and CMRO2 (sagittal sinus sampling) were measured before and after propranolol (2 mg/kg) in both the awake and anesthetized states. During the 4 months before CBF studies, the fasting blood glucose was greater in diabetic group than in the control group (11.0 +/- 0.3 vs. 4.0 +/- 0.1 mM, respectively). No difference occurred between groups in CBF or CMRO2. In the awake state, propranolol administration caused no CBF or CMRO2 changes. However, during anesthesia with 50 micrograms/kg fentanyl plus 10 mg/kg pentobarbital, propranolol administration decreased CBF in control, but not in diabetic, dogs. The authors' previous results showing increased CBF and CMRO2 with diabetes may be secondary to a differential response to acute surgical stress, a factor that was eliminated in this study. These results indicate that diabetes is associated with changes in the beta-adrenergic system that become evident under fentanyl/pentobarbital anesthesia.