Naloxone reversal of ischemic neurologic deficits in baboons is not mediated by systemic effects

A primate model was used to test the effects of opiate agonists and antagonists on neurologic function in conditions of acute and subacute cerebral ischemia. Fourteen baboons (Papio papio) underwent unilateral transorbital microsurgical occlusion of the middle cerebral artery. Blood pressure, heart rate, and core temperature were monitored continuously, and frequent arterial blood gas measurements were made. In selected baboons, cardiac output, cardiac filling pressures, and regional cerebral blood flow were also measured. Naloxone, administered intravenously, consistently reversed hemiparesis and hemiplegia for a period of 30 minutes in all baboons tested. The animals were tested over a period ranging from 4 hours to 8 days after occlusion. Morphine, administered intravenously to the hemiparetic baboons, rendered them totally hemiplegic; this effect also was reversed with naloxone. There were no significant changes in heart rate, blood pressure, core temperature, or arterial blood gas values after the administration of naloxone or morphine. Elevation of the mean arterial pressure with phenylephrine did not alter hemiplegia, despite elevation of the mean arterial pressure to a level 20 mm higher than the pressure measured after naloxone administration. Cardiac catherization studies showed no significant change in cardiac filling pressures or cardiac output after naloxone or morphine was administered. Isoproterenol, used to elevate cardiac output to 1 liter/min higher than the highest level measured after naloxone administration, produced no change in neurologic function. Regional cortical blood flow in the ischemic hemisphere did not change after naloxone administration. These studies indicate that naloxone can reverse, and morphine can exacerbate, focal ischemic neurologic deficit produced in baboons by contralateral occlusion of the middle cerebral artery. The observed change in neurologic function was not associated with or mediated by alterations in core temperature or cardiopulmonary function.