Cerebral blood flow and metabolism in dogs with chronic diabetes

Background: 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 β-adrenergic mechanisms. Methods: 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. Results: 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 μg/kg fentanyl plus 10 mg/kg pentobarbital, propranolol administration decreased CBF in control, but not in diabetic, dogs. Conclusions: 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 β-adrenergic system that become evident under fentanyl/pentobarbital anesthesia.