Effect of intracarotid and intraventricular morphine on regional cerebral blood flow and metabolism in pentobarbital-anesthetized dogs

Potent opiate analgesics, administered either epidurally, intrathecally, or intravenously, are a common adjunct to pain control in the perioperative period. Little is known, however, of the effects of opiate agonists on cerebral blood flow (CBF) and metabolism. Current studies are complicated by the hypotensive effects of these compounds and their route of administration. To circumvent these difficulties we studied the effects of intraventricular and intracarotid morphine sulfate, in doses that do not affect arterial blood pressure, on regional CBF and total cerebral oxygen consumption (CMRO₂) in pentobarbital-anesthetized dogs. Five dogs received 0.04 mg/kg morphine via intracarotid injection. Five additional dogs received 0.2 mg/kg morphine via ventricular cisternal infusion over 5 min, and five control dogs received mock cerebrospinal fluid at the same infusion rate. CBF was measured using the radiolabeled microsphere technique. Intracarotid morphine decreased neurohypophyseal blood flow to 58% of control, but it did not alter blood flow to any other brain region, except caudate nucleus, or cause a change in CMRO₂. Infusion of mock cerebrospinal fluid in the cerebral ventricles did not alter CBF or CMRO₂. Ventricular-cisternal perfusion of morphine caused a transient increase in CBF (24 ± 2 to 37 ± 6 mL min^-1 100 kg^-1) but had no effect on spinal cord blood flow or CMRO₂. Neurohypophyseal blood flow, however, decreased to 40% of control levels (480 ± 76 to 176 ± 42 mL min^{- 1} 100 kg^-1) after 2 min and gradually returned to control levels at 60 min. These data demonstrate that intracarotid and intraventricular morphine decreased blood flow to neurohypophysis, but only ventricular-cisternal perfusion of morphine altered blood flow to other brain regions, with the exception of caudate nucleus. Our results suggest a role for opiates in the control of CBF independent of changes in CMRO₂ when administered directly into the cerebrospinal fluid. This may have clinical implications when opiates are administered intrathecally or intravenously under conditions when the blood-brain barrier is disrupted. Opiates may also play a role in regulation of neurohypophyseal blood flow.