Effects of intravenous or subarachnoid morphine on cerebral and spinal cord hemodynamics and antagonism with naloxone in dogs.

In order to elucidate the possible mechanism(s) by which opiates may affect cerebral and spinal circulation, and cerebral metabolism, cerebral blood flow (CBF) and spinal cord blood flow (SCBF) were measured simultaneously following intravenous or subarachnoid administration of morphine in dogs lightly anesthetized with halothane. The mean values of CBF and SCBF, using hydrogen clearance methods, were 52.3 +/- 14.7 ml . 100 g-1 . min-1 (mean +/- 1 SD) and 22.3 +/- 9.0 ml . 100 g-1 . min-1, respectively. Morphine hydrochloride, 1 mg/kg, when given intravenously, reduced both CBF and SCBF to approximately 73% of the control values (P less than 0.01). These changes were accompanied by decreases in the cerebral metabolic rates for oxygen (CMRO2) and glucose (CMRglucose). The circulatory effects and, in part, the metabolic effects, were reversed by naloxone 40 microgram/kg iv. Prior administration of naloxone blocked the morphine effects on CBF and SCBF and suppressed the effects on CMRO2 and CMRglucose. The decreases in blood pressure (MAP) and heart rate (HR) were similar following morphine iv with or without prior administration of naloxone. However, when 0.2 mg morphine was injected into the spinal subarachnoid space, the above variables remained unaffected. Neither naloxone alone, nor its subsequent intravenous administration following spinal morphine, affected cerebral and spinal circulatory or cerebral metabolic indices. These results indicate that intravenous morphine affects both cerebral and spinal cord blood flow via the opiate receptors at supraspinal sites of action.