Cerebral autoregulation in young spontaneously hypertensive rats. Effect of sympathetic denervation.

Autoregulation of cerebral blood flow was studied with the hydrogen clearance method during development of hypertension in young spontaneously hypertensive rats. To examine the influence of sympathetic nerves on autoregulatory range, the unilateral superior cervical ganglion was removed 2 hours or 2 or 5 weeks before the study. Wall-to-lumen ratio of cerebral arteries was determined with freeze substitution technique. Basal blood pressures were 87 +/- 1 mm Hg (mean +/- SEM) at 4 weeks of age, 105 +/- 2 at 6 weeks, and 126 +/- 3 at 9 weeks, although resting cerebral blood flow was unchanged. Initially, cerebral blood flow remained relatively constant when the blood pressure was raised by intravenous infusion of phenylephrine. The upper limits of cerebral blood flow autoregulation in these groups were 110 +/- 4 mm Hg, 126 +/- 7, and 159 +/- 6 respectively. Acute ganglionectomy significantly lowered the upper limits (p less than 0.05), but chronic denervation did not affect the autoregulatory range. The wall-to-lumen ratios of cerebral arteries were 0.136 +/- 0.007 at 4 weeks and 0.130 +/- 0.005 at 9 weeks. These differences were not significant, nor did sympathetic denervation alter the ratio. These results indicate that (1) the upward shift of the autoregulation is closely related to a rise in the basal blood pressure, (2) acute interruption of sympathetic nerves modulates the autoregulatory range, and (3) adaptation of cerebral blood flow autoregulation to early developmental hypertension may be attributed to factors other than vascular smooth muscle hypertrophy.

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.

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 cerebral 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 encephalopathy 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 cerebral 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 technique 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 thalamus 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 restrained 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.

[Effects of hypo- or hyperglycemia on brain metabolism in experimental cerebral ischemia].

Glucose, lactate, pyruvate and adenosine triphosphate (ATP) concentrations in the supratentorial brain tissue frozen in situ were measured one hour after bilateral carotid occlusion in spontaneously hypertensive rats, of which blood glucose levels were varied by intraperitoneally injected insulin (hypoglycemia), saline (normoglycemia) and 50% glucose (hyperglycemia). Cerebral glucose concentrations as well as blood glucose levels were significantly increased in hyperglycemic animals, and decreased in hypoglycemic ones. Cerebral lactate, and lactate/pyruvate ratio at one-hour ischemia tended to increase in hyperglycemic animals comparing with those in normoglycemic ones, although cerebral ATP levels were slightly higher in the former. In hypoglycemic animals with one-hour ischemia, cerebral lactate was less increased but ATP was significantly reduced. It has been reported that hyperglycemia has vulnerable effects on brain metabolism of complete cerebral ischemia, presumably due to hyperglycemia-induced lactic acidosis of the brain. In incomplete cerebral ischemia as demonstrated in the present study, however, ATP concentrations remained at slightly higher level, despite tendency to more increase in lactate in hyperglycemic animals, indicating that high blood glucose level might be beneficial, rather than vulnerable, to incomplete cerebral ischemia. On the other hand, hypoglycemia causes more severe impairment of the brain energy metabolism because of an insufficient supply of substrates to the brain.

[Effects of alpha- and beta-adrenergic blockers on the lower limits of cerebral blood flow autoregulation in spontaneously hypertensive rats].

The effects of alpha- and beta-adrenergic blockers (phenoxybenzamine, PBZ and propranolol, PPL, respectively) on the cerebral (CBF) and cerebellar (CeBF) blood flow autoregulations were examined in spontaneously hypertensive rats. CBF and CeBF were measured during stepwise hemorrhagic hypotension using hydrogen clearance method. The lower limits of autoregulation for CBF beyond which blood flow was decreased steeply were 72% of the resting blood pressure level in the control, 56% in the PBZ treated group, and 80% in the PPL group. Similar tendency was observed in CeBF. These results indicate that PBZ leads to a downward shift while PPL to a slight upward shift of the lower limits of CBF and CeBF autoregulations, suggesting that alpha-adrenergic blockade has a favorable effect for the maintenance of cerebral blood flow during acute reduction of blood pressure.

Serial MR imaging in Creutzfeldt-Jakob disease.

Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful.

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.

Renal blood flow in acute cerebral ischemia in spontaneously hypertensive rats: effects of alpha- and beta-adrenergic blockade.

The influences of acute cerebral ischemia on renal hemodynamics were examined in spontaneously hypertensive rats in which cerebral ischemia was induced by bilateral carotid artery occlusion. Renal and cerebral blood flow were measured with a hydrogen clearance technique. Either phenoxybenzamine (0.5 mg/kg body wt) or propranolol (2 mg/kg) was given i.v. immediately after ischemia was induced to examine the drugs' effects on cerebral and renal hemodynamics. One hour after ischemia, cerebral blood flow was markedly reduced to 5, 3, and almost 0% of the preischemic value in the untreated, phenoxybenzamine-treated, and propranolol-treated rats, respectively. In contrast, renal blood flow at that time was decreased to 65, 88, and 67%, respectively. The calculated renal vascular resistance was similarly increased to 151% in the untreated and 136% in the propranolol-treated rats, but decreased to 82% in the phenoxybenzamine-treated rats. The present results indicate that in acute cerebral ischemia renal blood flow was considerably decreased with concomitant increased renal vascular resistance, and that such reduction in renal blood flow was minimized by alpha-adrenergic blockade but not by beta-blockade. It is concluded that activation of the alpha-adrenergic system in acute cerebral ischemia causes renal vasoconstriction.

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)

Cerebral blood flow and tissue metabolism in experimental cerebral ischemia of spontaneously hypertensive rats with hyper-, normo-, and hypoglycemia.

The present study was designed to clarify the effect of blood glucose level on cerebral blood flow and metabolism during and after acute cerebral ischemia induced by bilateral carotid ligation (BCL) in spontaneously hypertensive rats (SHR). Blood glucose levels were varied by intraperitoneal infusion of 50% of glucose (hyperglycemia), insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). Cerebral blood flow (CBF) in the parietal cortex and thalamus was measured by hydrogen clearance technique, and the supratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. In non-ischemic animals, blood glucose levels had no influence on the supratentorial lactate, pyruvate or adenosine triphosphate (ATP) concentrations. In ischemic animals, however, cortical CBF was reduced to less than 1% of the resting value at 3 hours after BCL. However, there were no substantial differences of CBF during and after ischemia among 3 glycemic groups. Cerebral lactate in the ischemic brain greatly increased in hyperglycemia (34.97 +/- 1.29 mmol/kg), moderately in normoglycemia (23.43 +/- 3.13 mmol/kg) and less in hypoglycemia (7.20 +/- 1.54 mmol/kg). In contrast, cerebral ATP decreased in hyperglycemia (0.93 +/- 0.19 mmol/kg) as much as it did in normoglycemia (1.04 +/- 0.25 mmol/kg), while ATP reduction was much greater in hypoglycemia (0.45 +/- 0.05 mmol/kg). At 1-hour recirculation after 3-hour ischemia, ATP tended to increase in all groups of animals, indicating the recovery of energy metabolism. Such metabolic recovery after recirculation was good in hypo- and normoglycemia, and was also evident in hyperglycemia. Our results suggest that hyperglycemia is not necessarily an unfavorable condition in acute incomplete cerebral ischemia.

Hyperbaric oxygen therapy in experimentally induced acute cerebral ischemia.

Effects of hyperbaric oxygen (HBO) on acute cerebral ischemia were studied in spontaneously hypertensive rats, which had the carotid artery bilaterally ligated. The animals were exposed to HBO (100% 02 at 2 ATA) for 30 min at 1 or 3 h after carotid ligation (treated group). Survival time and brain tissue metabolites were measured after HBO in these animals and compared with ischemic animals without HBO exposure (nontreated group). The animals treated at 3 h after ligation survived longer (6.5 +/- 0.7 h) than did nontreated ones (4.3 +/- 0.2 h) (P less than 0.05). The cerebral lactate increased much less in these treated animals (24.60 +/- 1.67 mM/kg) than in nontreated ones (31.78 +/- 1.68 mM/kg) (P less than 0.05). Cerebral ATP levels tended to decrease less in the former (0.66 +/- 0.17 mM/kg) than in the latter (0.59 +/- 0.07 mM/kg). When HBO started at 1 h after carotid ligation, however, there were no significant differences of survival time or brain metabolites between treated and nontreated groups of animals. The present results indicate that HBO administered at 3 h after brain ischemia prevents further increase in cerebral lactate and produces a slight but significant increase in survival time.

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

1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke-prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia. 2. The resting cerebral blood flow was comparable between the control and denervated animals. 3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham-operated control and denervated animals during ischaemia. 4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp.

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)

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.

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)

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)