Kazuyuki Nagatsuka

Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion

BACKGROUND The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. METHODS From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. RESULTS Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04: 0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/-0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP 0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08), or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7). CONCLUSIONS Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP.

Circulating CD34-Positive Cells Provide an Index of Cerebrovascular Function

Background—Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34- and CD133-positive cells present in peripheral blood, in maintenance of the vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction. Methods and Results—The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34- and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34- and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion. Conclusions—These results suggest a possible contribution of circulating CD34- and CD133-positive cells in maintenance of the cerebral circulation in settings of ischemic stress. Our data demonstrate the utility of a simple and precise method to quantify circulating CD34-positive cells, the latter providing a marker of cerebrovascular function.

Periventricular white matter lucency and cerebral blood flow autoregulation in hypertensive patients.

The goal of this study was to elucidate the association between the development of periventricular white matter lucency and autoregulation of cerebral blood flow in hypertensive patients through the arteriovenous oxygen saturation difference method. We studied 51 hypertensive patients who had previously suffered from minor strokes (lacunar infarction, 43; deep basal minor hemorrhage, 8). Patients were divided into three groups based on the findings of periventricular white matter lucency. We measured the absolute value of resting cerebral blood flow using the argon inhalation method, and stepwise reduction of blood pressure was obtained with patients on a tilting table. Intracerebral venous blood sampling was accomplished by direct cannulation into the jugular vein up to the jugular bulb. We calculated several cerebral circulatory parameters, such as cerebrovascular resistance and cerebral oxygen consumption, and also delineated individual autoregulation curves. Cerebrovascular resistance was significantly greater in patients with severe periventricular white matter lucency than in patients without it (P < .05). Impaired autoregulation was also significantly more prevalent in patients with more severe periventricular lesions (P < .05). Multiple regression analysis revealed that the impaired autoregulation was significant and an independent determinant of the severity of such periventricular lesions (R = .34, P < .05). In conclusion, our findings indicated that hypertensive patients with severe periventricular white matter lucency were more likely to have impaired autoregulation of cerebral blood flow and suggest that stricter blood pressure control is required in such patients to prevent deterioration of the cerebral microcirculation.

Aortic Arch Atherosclerotic Lesions and the Recurrence of Ischemic Stroke

Background and Purpose— Aortic arch atherosclerotic lesions are often associated with embolic brain infarction. We investigated the relationship between stroke recurrence and the characteristics of aortic arch atherosclerotic lesions. Methods— Among 487 stroke patients who underwent transesophageal echocardiography, 283 patients with brain embolism diagnosed without significant occlusive lesions (≥50%) in their cerebral arteries were included in this study. We measured the intimamedia thickness (IMT) and evaluated the extension and mobility of the aortic arch atherosclerotic lesions. During a mean follow-up period of 3.4 years, we investigated the relationship between stroke recurrence and the various characteristics of the aortic arch atherosclerotic lesions. Results— An IMT ≥4.0 mm was found in 67 patients (25.3%). In 51 of these patients, the aortic lesions extended to the origin of the branches of the arch. Recurrences of cerebral ischemic events were found in 32 patients (recurrence group) and not in the other 251 (nonrecurrence group). Aortic atheroma ≥4.0 mm (41% versus 22%), aortic atheroma extending to the branches (63% versus 39%), and both (38% versus 16%) were more frequently seen in the recurrence group than in the nonrecurrence group (P < 0.05, P < 0.1, P < 0.01, respectively). After adjustment for age and the presence of hypertension, an aortic atheroma that was ≥4.0 mm as well as extending to the branches was found to be an independent predictor of ischemic stroke recurrence (hazard ratio=2.42, P < 0.05). Conclusions— Stroke recurrence is associated with the severity of the atheroma (IMT ≥4.0 mm) and plaque extension to the branches.

Systolic Blood Pressure After Intravenous Antihypertensive Treatment and Clinical Outcomes in Hyperacute Intracerebral Hemorrhage The Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study

Background and Purpose— Blood pressure (BP) lowering is often conducted as part of general acute management in patients with acute intracerebral hemorrhage. However, the relationship between BP after antihypertensive therapy and clinical outcomes is not fully known. Methods— Hyperacute (<3 hours from onset) intracerebral hemorrhage patients with initial systolic BP (SBP) >180 mm Hg were included. All patients received intravenous antihypertensive treatment, based on predefined protocol to lower and maintain SBP between 120 and 160 mm Hg. BPs were measured every 15 minutes during the initial 2 hours and every 60 minutes in the next 22 hours (a total of 30 measurements). The mean achieved SBP was defined as the mean of 30 SBPs, and associations between the mean achieved SBP and neurological deterioration (≥2 points’ decrease in Glasgow Coma Score or ≥4 points’ increase in National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin Scale score 4–6 at 3 months) were assessed with multivariate logistic regression analyses. Results— Of the 211 patients (81 women, median age 65 [interquartile range, 58–74] years, and median initial National Institutes of Health Stroke Scale score 13 [8–17]) enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, mean achieved SBP was independently associated with neurological deterioration (odds ratio, 4.45; 95% confidence interval, 2.03–9.74 per 10 mm Hg increment), hematoma expansion (1.86; 1.09–3.16), and unfavorable outcome (2.03; 1.24–3.33) after adjusting for known predictive factors. Conclusions— High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes.

Atherosclerosis Found on Carotid Ultrasonography Is Associated With Atherosclerosis on Coronary Intravascular Ultrasonography

Little has been reported on the relationship between left main coronary artery atherosclerosis and carotid ultrasonographic results. We evaluated the association between carotid and coronary atherosclerosis assessed by coronary intravascular ultrasonography (IVUS) in 45 patients.

Vertebral Artery Occlusion in Duplex Color-Coded Ultrasonography

Background and Purpose— To establish the diagnostic criteria for the site of occlusion in the vertebral arteries (VAs) using duplex color-coded ultrasonography. Methods— In 128 consecutive patients who underwent conventional cerebral angiography, we prospectively measured the diameter, mean flow velocity (MV), peak systolic flow velocity, and end-diastolic flow velocity of both VAs. The diameter-ratio (diameter of contralateral VA divided by that of target VA) and MV-ratio (MV of contralateral VA divided by that of target VA) were determined. Based on the angiographic findings, we classified the VAs into 4 types (5 groups) as follows: (1) the origin of VA occlusion (Origin group: n=9); (2) VA occlusion before branching into the posterior inferior cerebellar artery (PICA) (Before group: n=10); (3A) symptomatic VA occlusion after branching into the PICA (After group: n=12); (3B) asymptomatic or hypoplastic occlusive VA after branching into the PICA (PICA end group: n=15); and (4) no significant occlusive lesions in the VA (Control group: n=194). Results— No flow signals in the VAs apparently indicated the Origin group. Preserved peak systolic flow velocity but end-diastolic flow velocity of zero cm/s indicated the Before group. MV <18 cm/s and MV-ratio ≥1.4 indicated the PICA end group or After group. Furthermore, these groups could be distinguished as follows: a diameter-ratio <1.4 indicated the After group. A diameter-ratio ≥1.4 indicated the PICA end group. Either MV ≥18 cm/s or MV <18 cm/s in combination with MV-ratio <1.4 indicated the Control group. Conclusion— Duplex color-coded ultrasonography can accurately diagnose the site of VA occlusion.

Transoral Carotid Ultrasonography

BACKGROUND AND PURPOSE We attempted ultrasonographic evaluation of the distal extracranial internal carotid artery (ICA) using the transoral method (transoral carotid ultrasonography [TOCU]). METHODS The subjects consisted of five healthy volunteers and seven stroke patients. Examinations were performed with a color Doppler flow imaging system equipped with convex array transducers (7 or 9.5 MHz), originally designed for transrectal use. After local anesthesia of the pharynx, we inserted a probe covered with thin gum transorally, touching the tip to the pharyngeal posterolateral wall. We then attempted to detect the ICA and measure flow velocity of the distal extracranial ICA using principal images obtained by TOCU. RESULTS TOCU was successfully performed in all subjects without any difficulty. In the healthy volunteers, the ICA was identified at a depth of 2.2+/-0.6 cm and visualized as a vertical linear vessel 2.9+/-0.3 cm in length and bent slightly backward. The diameter and mean flow velocity of the distal extracranial ICA were 4.7+/-0.2 mm and 50+/-7 cm/s, respectively. In the stroke patients, some remarkable findings were obtained, including a narrow ICA with low flow velocity in a patient with possible ICA dissection, a lucent echo without flow signal in a patient with acute cardioembolic ICA occlusion, and decreased ICA flow velocity in a patient with ipsilateral MCA stenosis. CONCLUSIONS These preliminary data demonstrate the potential applicability of TOCU to the evaluation of flow in the far distal extracranial ICA. TOCU definitely warrants further investigation in patients with carotid artery disease.

Genetic Variations of CYP2C9 in 724 Japanese Individuals and Their Impact on the Antihypertensive Effects of Losartan

CYP2C9, a drug-metabolizing enzyme, converts the angiotensin II receptor blocker losartan to its active form, which is responsible for its antihypertensive effect. We resequenced CYP2C9 in 724 Japanese individuals, including 39 hypertensive patients under treatment with losartan. Of two novel missense mutations dentified, the Arg132Gln variant showed a fivefold lower intrinsic clearance toward diclofenac when expressed in a baculovirus-insect cell system, while the Arg335Gln variant had no substantial effect. Several known missense variations were also found, and approximately 7% of the Japanese individuals (53 out of 724) carried one of the deleterious alleles (CYP2C9*3, *13, *14, *30, and Arg132Gln) as heterozygotes. After 3 months of losartan treatment, systolic blood pressure was not lowered in two patients with CYP2C9*1/*30, suggesting that they exhibited impaired in vivo CYP2C9 activity. CYP2C9*30 might be associated with a diminished response to the antihypertensive effects of losartan.

Increase in Circulating CD34-Positive Cells in Patients with Angiographic Evidence of Moyamoya-like Vessels

Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34-positive (CD34+) cells, in maintenance of cerebral blood flow. In this study, we investigated the link between the level of circulating CD34+ cells and neovascularization at ischemic brain. Compared with control subjects, a remarkable increase of circulating CD34+ cells was observed in patients with angiographic moyamoya vessels, although no significant change was observed in patients with major cerebral artery occlusion (or severe stenosis) but without moyamoya vessels. Our results suggest that the increased level of CD34+ cells associated with ischemic stress is correlated with neovascularization at human ischemic brain.