Osamu Shiokawa

Autoregulation of Cerebral Blood Flow in Young and Aged Spontaneously Hypertensive Rats (SHR)

Autoregulation of cerebral blood flow (CBF) to the controlled hemorrhagic hypotension was studied in young adult spontaneously hypertensive rats (SHR, 3.4 months of age) and aged SHR (20.3 months). There were no differences in average values for mean arterial pressure and baseline CBF between two groups of rats. During hypotension, however, CBF was more reduced in aged SHR than in young SHR, indicating that the lower limit of cerebral autoregulation is shifted to a higher level in aged SHR. Such upward shift of the autoregulation is likely due to a long-lasting hypertension which may lead to the diminished vasodilatory response of the brain to hypotension.

Upper limit of cerebral autoregulation during development of hypertension in spontaneously hypertensive rats--effect of sympathetic denervation.

The upper limit of cerebral autoregulation was studied in pre- or early established hypertension in spontaneously hypertensive rats (SHR). Cerebral blood flow (CBF) was measured with the hydrogen clearance method, and wall/lumen ratio of cerebral arteries was morphometrically measured with the freeze-substitution technique. To test autoregulation, phenylephrine was intravenously infused to cause stepwise increments of blood pressure. Unilateral superior cervical ganglionectomy was carried out to examine the effects of sympathetic denervation on CBF autoregulation and thickness of vascular wall. Resting blood pressure at 4 weeks, 3 months and 6 months of age were 89 +/- 3 mm Hg (mean +/- SEM), 140 +/- 6 and 165 +/- 6, respectively. Baseline CBF was slightly diminished with age; 50.6 +/- 9.2 ml/100 g/min at 4 weeks, 49.8 +/- 8.1 at 3 months and 44.1 +/- 5.6 at 6 months. The upper limit of autoregulation was markedly raised with age; 118 +/- 5 mm Hg at 4 weeks, 180 +/- 7 at 3 months and 208 +/- 10 at 6 months. Acute sympathetic denervation lowered the upper limits to 105 +/- 2, 162 +/- 4 and 185 +/- 7 mm Hg, respectively. On the other hand, in chronic denervation which was made at 4 weeks of age, the upper limit of autoregulation in the denervated hemisphere was slightly lower than that in innervated hemisphere at 2 months (165 +/- 5 and 178 +/- 6 mm Hg), and at 5 months (202 +/- 8 and 215 +/- 8 mm Hg) after ganglionectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral and cerebellar blood flow autoregulations in acutely induced cerebral ischemia in spontaneously hypertensive rats - transtentorial remote effect

Autoregulation of cerebral (CBF) and cerebellar blood flow (CeBF) was studied before, during and after acutely induced cerebral ischemia in spontaneously hypertensive rats. Cerebral ischemia of the supratentorial portion was induced for one hour by bilateral carotid artery ligation (BCL). The animals were artificially ventilated and the blood flow was measured with a hydrogen clearance technique. To test the autoregulation, the blood pressure was stepwise lowered by bleeding and maintained at a new level, i.e. 15% or 30% lower than the baseline values before, during and after cerebral ischemia. At the preischemic state, CBF and CeBF were 52.1 +/- 6.2 and 58.9 +/- 4.6 ml/100 g/min (mean +/- SEM), of which autoregulations were normally preserved. Following BCL, CBF was markedly decreased to about 10% of control value while CeBF was minimally reduced to 46.9 +/- 8.6 ml/100 g/min (80%). At the ischemic state, CBF became almost zero flow during hypotension. CeBF was also reduced to 74% and further to 58% of the resting value by 15% and 30% decrease in the blood pressure, respectively, indicating impaired CeBF autoregulation. At the 30 min post-ischemic state, CBF was recovered to 48.0 +/- 4.9 and CeBF to 53.9 +/- 5.4 ml/100 g/min. Autoregulation of CBF was still abolished, whereas CeBF was kept constant by 15% fall of blood pressure and slightly reduced to 84% by 30% hypotension, indicating almost recovery of CeBF autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Disruption of blood-brain barrier following bilateral carotid artery occlusion in spontaneously hypertensive rats. A quantitative study.

The present study was designed to clarify the relationship of cerebral blood flow (CBF) to blood-brain barrier (BBB) in the ischemic brains with or without recirculation, which were produced by clipping of both common carotid arteries in spontaneously hypertensive rats. CBF was measured by the hydrogen clearance method and BBB function was evaluated by the permeability of 131I-albumin and Evans blue dye. Cortical CBF was reduced from 48.8 +/− 9.5 to 4.0 +/− 1.2 ml/100 gm/min during 1 hr ischemia and further to 2.6 +/− 0.3 ml/100 gm/min during 3 hrs ischemia, while thalamic CBF was reduced much less from 50.0 +/− 3.6 to 17.9 +/− 6.5 ml/100 gm/min and to 17.5 +/− 11.0 ml/100 gm/min, respectively. There was no increase in permeability to protein tracers observed in such 1 hr or 3 hrs ischemic brain. Both cortical and thalamic CBF were markedly increased 2.5 to 6 fold of resting values at 5 min after recirculation in the 1 hr ischemic brain. In the 3 hrs ischemic brain, however, both CBF were only slightly increased but never restored to the resting level even at 30 min after recirculation. In such reperfused brains, exudation to Evans blue dye was observed in none of 16 animals with 1 hr ischemia, but in 18 of 23 with 3 hrs ischemia. Disruption of BBB was twice more frequent in the cortex (77.8%) than in either thalamus (33.3%) or hippocampus (33.3%). Permeability index of 131I-albumin (brain albumin/blood albumin) was significantly higher in the ischemic areas stained with blue dye (2.07 +/− 0.45%) than in non-ischemic control brain (0.10 +/− 0.01%).(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of bilateral sympathetic innervation on cerebral blood flow autoregulation in the thalamus

Effects of bilateral sympathetic innervation on the regulation of cerebral blood flow to the thalamus were examined in spontaneously hypertensive rats (SHR). The superior cervical ganglion was removed on one side or bilaterally, and blood flow in the thalamus was repeatedly measured with a hydrogen clearance technique during a stepwise increase in arterial pressure. Regional blood flow in the thalamus was unchanged following acute ganglionectomy: 55 +/- 6 ml/100 g/min in the intact rats and 56 +/- 4 in the denervated rats. Sympathectomy on one side neither had effects on the pressure-flow relationship nor on the blood pressure levels of upper limits of autoregulation in the ipsilateral thalamus. In contrast, bilateral sympathetic denervation impaired the autoregulatory function in the thalamus and the upper limits were significantly lower than those in intact rats: 206 +/- 8 vs 226 +/- 10 mm Hg, respectively (P less than 0.02). It is concluded that overlapping innervation of sympathetic nerves has an important role in regulation of blood flow to the thalamus during an acute rise in arterial pressure in SHR.

Impairment of cerebellar blood flow autoregulation during cerebral ischemia in spontaneously hypertensive rats.

Participation of the autonomic nervous system in cerebellar autoregulation during supratentorial cerebral ischemia induced by bilateral carotid ligation was studied using 23 spontaneously hypertensive rats. Cerebral and cerebellar blood flows measured by a hydrogen clearance method were evaluated under stepwise hemorrhagic hypotension before and 30 minutes after ligation and after a 30-minute recirculation period following 1 hour of ligation. alpha-Adrenergic blockade with phenoxybenzamine, beta-adrenergic blockade with propranolol, and muscarinic cholinergic blockade with atropine were selectively administered before ligation for inhibition of sympathetic and parasympathetic tone. Cerebral blood flow autoregulation was severely impaired during and after cerebral ischemia in each treatment group. During cerebral ischemia, cerebellar blood flow autoregulation was also significantly impaired in both the propranolol and atropine groups although it was better preserved in the phenoxybenzamine group. After recirculation, cerebellar blood flow autoregulation recovered almost to the normal range in the phenoxybenzamine and atropine groups but remained impaired in the propranolol group. Our results suggest that impaired cerebellar blood flow autoregulation in supratentorial cerebral ischemia is partly modulated by the alpha-adrenoceptor system, which is activated by hypertensive stimuli and cerebral ischemia, leading to vasoconstriction in the cerebellum.

Alpha- and Beta-Adrenergic Receptors of Noradrenergic Innervation Modulate the Lower Limits of Cerebral and Cerebellar Blood Flow Autoregulation in Spontaneously Hypertensive Rats

The effects of alpha- and beta-adrenergic receptors on the lower limits of cerebral (CBF) and cerebellar blood flow (CeBF) autoregulation were examined in spontaneously hypertensive rats. CBF and CeBF were measured during hemorrhagic hypotension in rats treated with adrenergic blockers, phenoxybenzamine (PBZ) or propranolol (PPL), using a hydrogen clearance method. The lower limits for CBF beyond which blood flow was decreased steeply were 72% of resting values in the control, 44 in the PBZ and 80 in the PPL group. Similar tendency was also observed for CeBF. In the control group, the reducing rates of mean arterial pressure (MAP) to decrease CBF by 15 and 30% of the resting values were 33% (58 mm Hg) of the resting MAP and 46% (80 mm Hg), respectively, and those to reduce CeBF to the same extent were 35% (61 mm Hg) and 52% (92 mm Hg), respectively. In the PBZ group, the respective reducing rates of MAP were 52% (71 mm Hg) and 65% (88 mm Hg), respectively, for CBF and 50% (68 mm Hg) and 65% (88 mm Hg), respectively, for CeBF. In contrast, in the PPL group, those rates were 22% (39 mm Hg) and 32% (56 mm Hg), respectively, for CBF, and 23% (40 mm Hg) and 30% (52 mm Hg), respectively, for CeBF, being significantly smaller than those in the control and the PBZ groups (p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute superior cervical ganglionectomy on cerebral blood flow and metabolism in stroke-prone spontaneously hypertensive rats subjected to cerebral ischaemia

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Transient Encephalopathy Related to Rapidly and Markedly Elevated Blood Pressure in Acute Stage of Hypertensive Cerebral Hemorrhage — Relationship to Hypertensive Encephalopathy — A Case Report

A seventy-two-year-old man with hypertensive cerebral hemorrhage acutely developed severe headache, nausea, vomiting, agitation, and disorientation with abrupt rise in blood pressure on the sixth day after the onset. At that time, there were no remarkable changes in focal neurologic deficits, and repeated brain CT scans revealed a small hematoma located in the right basal ganglia without further enlargement or herniation. Blood chemistry and arterial gas analysis were within the normal ranges except for a slight rise in blood urea nitrogen. Similar episodes occurred three times within two days, and each time the cere bral symptoms disappeared in accordance with lowering of blood pressure by antihypertensive therapy. Complication of hypertensive encephalopathy was strongly suggested. The authors discuss the pathophysiology of this encephalo pathy in relation to cerebral hemorrhage.

Effects of Intravenous Glycerol on Cerebral Blood Flow and Tissue Metabolism in Acute Cerebral Ischemia in Spontaneously Hypertensive Rats

The effects of antiedematous agent with intravenous 10% glycerol on cere bral blood flow (CBF) and metabolism were studied in acute cerebral ischemia experimentally induced by bilateral carotid artery occlusion in spontaneously hypertensive rats (SHR). CBF was measured by the hydrogen clearance tech nique and brain tissue metabolites such as lactate, pyruvate and ATP in the ischemic brain frozen in situ were determined by the enzymatic method. In comparison with saline-infused SHR, the reduction of CBF in the thala mus following carotid occlusion was significantly small in the glycerol treated SHR. Supratentorial ATP concentration in the 3 hr-ischemic brain was reduced in both groups of rats, but its reduction was significantly smaller in the glycerol- infused group than the other. Lactate and lactate/pyruvate ratio tended to be less increased in the glycerol rats, indicating that ischemic metabolism was re strained by the treatment. The present results strongly suggest that intravenous glycerol is effective against acute cerebral ischemia from the view point of cerebral hemodynamic and metabolism.