Neurogenic Control of Cerebral Blood Flow in the Baboon. Effects of Alpha Adrenergic Blockade With Phenoxybenzamine on Cerebral Autoregulation and Vasomotor Reactivity to Changes in Pa CO ₂

Abstract

Abstract• Cerebral autoregulation was studied in the baboon by increasing and decreasing cerebral perfusion pressure (CPP) before and after intravenous administration (1..5 mg per kilogram) of a long-acting alpha adrenergic blocker, phenoxybenzamine (PBZ). Likewise, cerebral vasomotor reactivity to changes of arterial carbon dioxide tension (Paco 2 ) was examined before and after PBZ.In order to permit quantitative analysis, cerebral autoregulation (A.I.) and chemical vasomotor reactivity (C.I.) were expressed as indices whereACPP " ' " ""*• APaco 2 ' Following the intravenous injection of PBZ, cerebral auioregulatory vasoconstriction was impaired as CPP was increased. Cerebral vasomotor reactivity to changes in Paco 2 was altered both during hyperventilation hypocapnia (HV) and hypercarbia induced by inhalation of 5% carbon dioxide if alterations of CPP brought about by these procedures were taken into consideration. During hypocapnia C.I. was reduced 30% and during hypercarbia C.I. was increased 10%.It is concluded that PBZ reduces the vasoconstrictor tonus of cerebral vessels during hypocapnia and raised CPP. It also enhances the vasodilator response to CO, inhalation. Additional Key Words

Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation

“…For example, in primates, both unilateral superior cervical ganglionectomy and alpha adrenergic blockade with intravenous r------l 12 phenoxybenzamine enhance the maintenance of CBF in the face of hypotension, shifting the autoregulation curve acutely to the left (7,14) and impairing the autoregulatory response to acute increases in BP (14,44). However, these effects are mainly reversed after chronic sympathectomy (7,11).…”

Parasympathetic cholinergic control of cerebral blood flow in dogs.

“…For example, if the cerebral metabolism increased, then cerebral venous oxygen tension would either remain the same (if the flow exactly matched the metabolism) or would decrease (if the increased metabolism exceeded the increase in flow). Recent studies of intra-arterial infusion of atropine 5 and neostigmine" indicate that cholinergic blockade or cholinesterase inhibition do not alter cerebral metabolic rate for oxygen. It is therefore unlikely that intra-arterial acetylcholine infusion would increase the cerebral metabolic rate for oxygen.…”

“…4 More recently, intravertebral atropine was shown to suppress the dilation resulting from inhalation of 5% CO 2 , 5 and intravertebral neostigmine enhanced cerebral vasodilator reactivity to CO 2 .…”

Cerebral infarction in the Mongolian gerbil exacerbated by phenoxybenzamine treatment.

“…The low dose (2 mg per kilogram) of phenoxybenzamine is slightly higher than the 1.5 mg per kilogram dose given intravenously by Kawamura et al 29 to decrease vasoconstrictor tone in cerebral vessels during hypocapnia and increased cerebral perfusion pressure, and slightly higher than the 0.7 mg per kilogram dose given via the carotid artery to stroke patients by Meyer et al, 1 * which appeared to decrease hemispheric metabolism. We slightly increased the dosage to compensate for any loss due to our use of an intraperitoneal route.…”