Abstract-In a canine model of transient global cerebral ischemia, the correlation between the decrease in baroreflex sensitivity (BRS) following 5-min ischemia and the degree of ischemia or post-ischemic hypoperfusion was investigated. Although the medulla oblongata and the cerebral cortex suffered a similar degree of ischemia, the extent of post-ischemic decrease in BRS was inversely correlated with the re sidual blood flow during ischemia in the medulla, but not with that in the cerebral cortex. A similar degree of post-ischemic hypoperfusion occurred in the medulla and the cerebral cortex.However, the extent of decrease in BRS was not correlated with the degree of hypoperfusion, and the cortical EEG was not significantly affected. These results suggest that the decrease in BRS may be due to the functional damage in the medulla and that the selective decrease in BRS without concomitant impair ment of the EEG cannot be ascribed to the regional difference in the degree of isch emia or post-ischemic hypoperfusion.

1 A possible cerebroprotective effect of a chemically stable prostacyclin analogue, beraprost sodium, was investigated in a canine model of cerebral ischaemia. Cerebral ischaemia was produced by the combined occlusions of the left subclavian and the brachiocephalic arteries with preceding ligations of the intercostal arteries. 2 The decrease in baroreceptor reflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, following 5 min ischaemia was used to assess the cerebroprotective effect.3 Beraprost (1ygkg-1min-1 i.v., infused for 15min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1pgkg-'min-1 i.v.) failed to show such a protective effect, its inhibitory effect on ADP-induced platelet aggregation was as potent as that of the highe ,e. 4 The extent of decrease in BRS was inversely correlated with the extent of the residual blood flow in the medulla oblongata during ischaemia. Since beraprost did not affect the extent of the residual blood flow during ischaemia, its cerebroprotective effect could not be ascribed to the reduction of the degree of ischaemia by increasing collateral blood flow to the brain. 5 Post-ischaemic reduction of the regional blood flow in the medulla and the cerebral cortex was completely prevented by the higher dose of beraprost. 6 The present study suggests that the cerebroprotective effect of beraprost may be independent of its anti-aggregatory and vasodilator effects. It is possible that the protection may be due to a prostacyclinlike cytoprotective effect through membrane stabilization.

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Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) antago nist, failed to protect the vagal component of reflex bradycardia from 5-min global cerebral ischemia in dogs under pentobarbital anesthesia. On the other hand, MK-801 completely prevented the develop ment of the post-ischemic cerebral hypoperfusion without affecting the cerebral blood flow in sham operated animals. The results suggest that NMDA receptors may participate in the development of the secondary disturbance of the cerebral circulation, but are not involved in the post-ischemic dysfunction of the baroreflex system.The non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 has been used to investigate the pathological role of excitatory amino acid in ischemic neuronal injury (1). In the present study, we examined the effect of MK-801 on the post-ischemic dysfunction of the vagal baroreflex and the secondary cerebral hypoperfusion in a canine model of transient global cerebral ischemia (2, 3).Mongrel dogs of either sex, weighing about 7 to 15 kg, were anesthetized with sodium pentobarbital (32 mg/kg, i.v. followed by an infusion of 3.2 mg/kg/hr, i.v.). The animals were artificially ventilated (a tidal volume of 20 ml/kg at a rate of 20 breaths/min) and immobilized with suxamethonium chloride (2 mg/kg, i.v., followed by an infusion of 1 mg/kg/hr, i.v.). Arte rial Pot and Pco2 were maintained at about 100 and 35 mmHg, respectively, providing an appropriate volume of 02 and CO2 gasses via a respirator. The rectal temperature was maintained at about 38°C using a heat ing pad and lamp.Arterial blood pressure was measured from the left femoral artery by means of a pressure transducer (Nihon Kohden, TP-200T), and heart rate was meas ured by a heart rate counter (Nihon Kohden, AT 600G) triggered by the lead II ECG. The cortical EEG was continuously monitored from the parietal skull us ing a frequency analyzer (Nihon Kohden, OEE-7102). The reflex increase in pulse interval by 1-phenylephrine hydrochloride (0.3 to 10 ,ug/kg injected into the left cephalic vein) was correlated with the increase in mean blood pressure by a method of least squares. The slope of the regression line (msec/mmHg) was used as a meas ure of baroreflex sensitivity (BRS).Incomplete global cerebral ischemia was produced by a 5-min occlusion with clamps of the brachiocephalic artery and the left subclavian artery following ligations of about 14 intercostal arteries. Regional cerebral blood flow (rCBF) in the dorsal medulla oblongata was con tinuously measured by a tissue flow monitor (Unique Medical, UMW-101) using a plate-type thermocouple electrode, and the mean residual blood flow during ischemia was calculated as an index of the severity of ischemia (2). Furthermore, the absolute value of rCBF in the dorsal medulla oblongata was obtained by a hy drogen clearance method (4).MK-801 (Research Biochemical, Inc.) was dissolved in saline and infused according to the dosage regimen by Michenfelder et al. (5), which produces the steady plasma concentrati...

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