Kenji Kusuda

Effects of High Atmospheric Pressure and Oxygen on Middle Cerebral Blood Flow Velocity in Humans Measured by Transcranial Doppler

BACKGROUND AND PURPOSE There are several reports that have studied the effects of hyperbaric oxygen (HBO) on cerebral blood flow (CBF). However, most of the reports have been of animal experiments, and human studies are few so far. The aim of this study is to clarify the relationship between HBO and CBF in humans. METHODS Middle cerebral arterial blood flow velocity (MCV) was measured using transcranial Doppler (TCD) technique in a multiplace hyperbaric chamber. The Doppler probe was fixed on the temporal region by a head belt, and the transcutaneous gas measurement apparatus (tcPO2 and tcPCO2) was fixed on the chest wall. MCV and transcutaneous gas were measured continuously in eight healthy volunteers under four various conditions: 1 atmosphere absolute (ATA) air, 1 ATA oxygen (O2), 2 ATA air, and 2 ATA O2. On the next step, the effect of environmental pressure was studied in another eight healthy volunteers, in whom the tcPO2 was kept at almost the same level under conditions of both 1 ATA and 4 ATA by inhaling oxygen at 1 ATA. RESULTS MCV of 1 ATA O2, 2 ATA air, and 2 ATA O2 decreased, and tcPO2 increased significantly in comparison with that of 1 ATA air. A significant difference in MCV was observed between the O2 group and the air group under the same pressure circumstance. On the other hand, there were no differences in MCV or tcPO2 between 4 ATA air and 1 ATA plus O2, and the influence for the MCV of the environmental pressure was not observed. CONCLUSIONS We conclude that hyperoxemia caused by HBO reduces the CBF, but the high atmospheric pressure per se does not influence the CBF in humans.

Cerebrospinal Fluid Lactate in Patients with Hepatic Encephalopathy

Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 16 patients with hepatic encephalopathy before and/or after treatment. CSF lactate was significantly increased to 1.92 +/- 0.11 mmol/l in hepatic encephalopathy before the treatment in comparison to 1.40 +/- 0.05 mmol/l in control subjects. In 9 of 11 patients with moderate or stage 2 encephalopathy, CSF lactate levels were below 2 mmol/l. In contrast, in 4 of 5 patients with stage 3-4 encephalopathy, CSF lactate levels were higher than 2 mmol/l. CSF lactate was decreased with the recovery of neurological symptoms by the treatment. These findings indicate that CSF lactate levels reflect the severity of metabolic impairment of the brain. Hypocapnia was frequently observed in these encephalopathic patients, and arterial PCO2 correlated inversely with CSF lactate and linearly with CSF HCO3-, suggesting that CSF lactic acidosis contributes to hyperventilation in hepatic encephalopathy. It is concluded from present results that metabolic disorder of neuronal cells might be one of the important factors for the development of hepatic encephalopathy.

ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack

Background and Purpose— Several risk scores have been developed to predict the stroke risk after transient ischemic attack (TIA). However, the validation of these scores in different cohorts is still limited. The objective of this study was to elucidate whether these scores were able to predict short-term and long-term risks of stroke in patients with TIA. Methods— From the Fukuoka Stroke Registry, 693 patients with TIA were followed up for 3 years. Multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke. The discriminatory ability of each risk score for incident stroke was estimated by using C-statistics and continuous net reclassification improvement. Results— The multivariable-adjusted Cox proportional hazards model revealed that dual TIA and carotid stenosis were both significant predictors for stroke after TIA, whereas abnormal diffusion-weighted image was not. ABCD3 (C-statistics 0.61) and ABCD3-I (C-statistics 0.66) scores improved the short-term predictive ability for stroke (at 7 days) compared with the ABCD2 score (C-statistics 0.54). Addition of intracranial arterial stenosis (at 3 years, continuous net reclassification improvement 30.5%; P<0.01) and exclusion of abnormal diffusion-weighted imaging (at 3 years, continuous net reclassification improvement 24.0%; P<0.05) further improved the predictive ability for stroke risk until 3 years after TIA. Conclusions— The present study demonstrates that ABCD3 and ABCD3-I scores are superior to the ABCD2 score for the prediction of subsequent stroke in patients with TIA. Addition of neuroimaging in the ABCD3 score may enable prediction of long-term stroke risk after TIA.

Regional cerebral blood flow autoregulation in normotensive and spontaneously hypertensive rats--effects of sympathetic denervation.

The present study was designed to investigate the effect of acute sympathetic denervation on the regional cerebral blood flow (CBF) autoregulation during acute elevation of blood pressure in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). CBF to the parietal cortex and thalamus was measured by the hydrogen clearance method and, to test autoregulation, systemic arterial blood pressure was elevated by intravenous infusion of phenylephrine. Superior cervical ganglia were removed on both sides to interrupt sympathetic innervation in the deeper structures of the brain. Acute bilateral sympathetic denervation did not alter the resting blood pressure or CBF in either SHR or WKY. In innervated SHR, resting mean arterial pressure (MAP) was 165 +/- 5 mm Hg (mean +/- SEM) and the upper limit of autoregulation in the cortex was 210 +/- 3 mm Hg, which was significantly lower than that in the thalamus (229 +/- 3 mm Hg, p less than 0.02). In bilaterally denervated SHR, the upper limits were lowered to 193 +/- 4 mm Hg in the cortex (p less than 0.02 vs. innervated SHR) and to 207 +/- 5 mm Hg in the thalamus (p less than 0.02 vs. innervated). In WKY, resting MAP was approximately 55 mm Hg lower than that in SHR. Acute denervation reduced the upper limits from 142 +/- 3 mm Hg to 130 +/- 4 in the cortex (p less than 0.05) and from 158 +/- 4 to 145 +/- 4 in the thalamus (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Sex Differences in Short-Term Outcomes After Acute Ischemic Stroke The Fukuoka Stroke Registry

Background and Purpose— Variable sex differences in clinical outcomes after stroke have been reported worldwide. This study aimed to elucidate whether sex is an independent risk factor of poor functional outcome after acute ischemic stroke. Methods— Using the database of patients with acute stroke registered in the Fukuoka Stroke Registry in Japan from 1999 to 2013, 6236 previously independent patients with first-ever ischemic stroke who were admitted within 24 hours of onset were included in this study. Baseline characteristics were assessed on admission. Study outcomes included neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin Scale score, 3–6 at discharge). Logistic regression analyses were performed to evaluate the association between sex and clinical outcomes. Results— Overall, 2398 patients (38.5%) were women. Severe stroke (National Institutes of Health Stroke Scale score, ≥8) on admission was more prevalent in women than in men. The frequency of neurological improvement or deterioration during hospitalization was not different between the sexes. After adjusting for possible confounders, including age, stroke subtype and severity, risk factors, and poststroke treatments, it was found that female sex was independently associated with poor functional outcome at discharge (odds ratio, 1.30; 95% confidence interval, 1.08–1.57). There was heterogeneity of the association between sex and poor outcome according to age: women had higher risk of poor outcome than men among patients aged ≥70 years, but no clear sex difference was found in patients aged <70 years. Conclusions— Female sex was associated with the risk of poor functional outcome at discharge after acute ischemic stroke.

NAD(P)H oxidase p22phox C242T polymorphism and ischemic stroke in Japan: the Fukuoka Stroke Registry and the Hisayama study.

The C242T polymorphism of p22phox, a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi‐squared test revealed that the T‐allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate‐adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72–1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS‐7 cells cotransfected with Nox4 and p22phox of each genotype. The superoxide‐producing activity in those cells expressing p22phox with the T allele was not significantly different from that in cells expressing p22phox with the C allele. The present results suggest that the p22phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan.

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)

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.

Brain ischemia following bilateral carotid occlusion during development of hypertension in young spontaneously hypertensive rats : Importance of morphologic changes of the arteries of the circle of Willis

The present study was designed to examine the effect of morphologic changes of the arteries of the circle of Willis on cerebral blood flow (CBF) and metabolism in young spontaneously hypertensive rats (SHR). CBF in the parietal cortex was measured by the hydrogen clearance method before and during a one-hour bilateral carotid artery occlusion (BCO), and supratentorial brain metabolites were determined by standard enzymatic methods at a one-hour BCO. The internal diameters of the main arteries of the circle of Willis were estimated morphologically. With increase in age, systemic arterial pressure at rest was significantly raised, while cortical CBF tended to decrease and calculated cerebral vascular resistance increased. During BCO, CBF and supratentorial metabolism (adenosine triphosphate and lactate/pyruvate ratio) tended to be better preserved in two-month-old rats as compared with those in one- or three-month-old rats. The internal diameter of the posterior commu nicating artery (PcomA) was significantly smaller in the one-month-old group than in the other groups, while the diameter of the internal carotid artery was significantly smaller in rats aged three months than those in rats aged one or two months. It is indicated that cortical CBF reduction and impairment of supratentorial metabo lism following occlusion of carotid arteries, at least in part, depend on the morphologic changes of the arteries of the circle of Willis associated with age and development of hypertension in young SHR.

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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