Aktmct-Cortical monoamine changes during ischemic episodes of varied duration and their sequence of changes following cerebral reperfusion were studied in the gerbil. Forty-one percent of 280 animals exhibited signs of cerebral hemispheric ischemia (stroke) after unilateral common carotid artery occlusion. Norepinephrine (NE) levels decreased after 60 min in the occluded hemisphere of stroked animals but dopamine (DA) levels were unaltered. 5-Hydroxytryptamine (5-HT) levels became bilaterally reduced in both stroked and non-stroked animals as soon as 5 min after occlusion.Upon reperfusion after periods of 30 or 60 min of occlusion there was a bilateral rebound increase of cortical NE and DA levels to well above control values in stroked and non-stroked animals. 5-HT levels remained reduced in both groups.

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.

The incidence of ischemia induced by carotid occlusion decreased from 44% to 26% in PCPA-treated animals, which also suggests that depletion of 5-HT available for neuronal release prior to the induction of ischemia may reduce stroke incidence by limiting impairment of collateral vasocapacitance. PCPA pretreatment did not influence the development of edema in the occluded hemisphere of ischemic animals once ischemia was established.

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SUMMARY Cerebral hemispheric blood flow and metabolism were measured before and after therapy with intracarotid infusion of combined PBZ and PPL in IS patients with recent cerebral infarction. HBF was unaltered despite decrease in cerebral perfusion pressure. Cerebral hemispheric oxygen consumption and carbon dioxide production decreased while cerebral hemispheric lactate production increased.Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion. CSF HVA increased, indicating altered DA turnover. CSF SHIAA levels also increased, suggesting altered SHT turnover after PBZ and PPL. Release of cyclic AMP from ischemic brain into cerebral venous blood seen in the steady state was abolished after therapy.Cerebral hemodynamic studies suggest a functional balance between monoaminergic neurogenic influences in the control of cerebral circulation. Imbalance of such controlling factors in ischemic brain may lead to paradoxical vascular responses to induced hypertension and hypotension. PBZ and PPL enhance such responses perhaps by increasing central neurotransmitter turnover and release.Further shift toward cerebral anaerobic metabolism may occur in ischemic brain following the use of phenoxybenzamine and propranolol.Worsening of neurological deficit occurred in four cases. Combined therapy with PBZ and PPL does not appear beneficial in the therapy of patients with recent stroke.