N-Acetylcysteine Alleviates the Progression of Chronic Kidney Disease: A Three-Year Cohort Study.

Background and Objectives: The prevalence of chronic kidney disease (CKD) is approximately 10% of the population in many countries. CKD progresses to end-stage renal disease (ESRD), resulting in adverse outcomes, prolonged hospitalization, and increased healthcare costs. Therefore, reducing CKD progression to ESRD is recognized as an important health issue. Materials and Methods: Data from the study participants with stage 3 to stage 5 CKD (n = 7668) were collected from the National Health Insurance (NHI) program in Taiwan (1 November 2014 to 31 December 2020). CKD patients who had ingested or not ingested N-acetylcysteine (NAC) for three years were divided into the study group (NAC users; n = 165) and the control group (NAC non-users; n = 165) to explore whether NAC use could alleviate CKD progression and reduce the risks associated with hemodialysis in CKD patients. Results: The levels of serum creatinine (SCr) and estimated globular filtration rate (eGFR) were nearly unchanged and/or slightly changed in NAC users, but the SCr levels were slightly increased, and the eGFR levels were significantly decreased in NAC non-users at the six-month interval during the three years. A statistical difference was observed between the two groups for both levels from 12 months to 36 months. The incidence rate of hemodialysis was significantly lower in NAC users than in non-NAC users (4.8% vs. 12.7%, Wald test = 5.947, p = 0.015, OR = 34.9). These results indicated that NAC use may improve renal function of CKD patients by modulating SCr and eGFR and, in turn, reducing the risk of hemodialysis. Conclusions: We investigated whether NAC could be used to reduce CKD progression to ESRD. For the three-year retrospective study, the incidence rate of hemodialysis was significantly lower in NAC users than in non-NAC users via modulating SCr and eGRF levels. NAC use might be a useful clinical approach for reducing CKD progression to ESRD.

Endoluminal release of ureteral ligature after hysterectomy.

Iatrogenic ureteral injury is a well-recognized complication of abdominal total hysterectomy. We report a case of a 57-year-old female who underwent abdominal total hysterectomy for a uterine myoma and experienced severe right flank pain postoperatively. The imaging study displayed an obstruction of the right distal ureter. Under ureteroscopy, an extraluminal ligature was released with a holmium:yttrium-aluminum-garnet laser. The stenotic segment was immediately relieved. Two months later, the intravenous urogram illustrated patency of the distal ureter with regression of right hydronephrosis. There was no recurrent hydronephrosis during 1 year of follow-up.

Plasma levels of transforming growth factor-beta 1 before and after removal of low- and high-grade astrocytomas.

Transforming growth factor-beta 1 (TGF-ß1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-ß1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-ß1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-ß1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-ß1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p<0.05); there was no significant change in TGF-ß1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-ß1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-ß1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-ß1 might be useful as a tumor marker for astrocytomas.

Arrested growth and spontaneous tumor regression of partially resected low-grade cerebellar astrocytomas in children.

PURPOSE: The prognosis of children with low-grade cerebellar astrocytoma who have partial resection of tumor is largely unpredictable. The purpose of this study was to review the long-term outcome of such patients. METHODS: The medical charts, imaging findings, operative notes, histopathological reports, and survival times of 12 patients with cerebellar astrocytoma were reviewed. RESULTS: Five patients had total resection and seven had partial resection. Nine patients had grade I histology and three patients had grade II. Follow-up duration ranged from 3 to 25 years. Among the seven patients with residual tumor, five had tumor progression, one had arrested tumor growth, and one had spontaneous tumor regression. Five patients with partial resection received radiotherapy and three had malignant transformation of tumor during follow-up. Six patients, including five who had partial resection, underwent a second operation. One patient with partial resection died of pneumonia 23 years after surgery. CONCLUSIONS: Patients with complete tumor resection had a better prognosis than patients with partial resection. For patients with partial resection, we recommend a "wait and see" policy with surveillance using MRI. The phenomenon of arrested tumor growth and spontaneous tumor regression in patients with cerebellar astrocytoma who have subtotal resection warrants further study.

Attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage by the bronchodilator KMUP-3.

Delayed cerebral vasospasm is a main cause of morbidity and mortality as well as poor outcome in patients following aneurysmal subarachnoid hemorrhage (SAH). In this study, the effect of the bronchodilator KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) on basilar artery narrowing, neurological outcome, and expression of rhoA/rho kinase II (ROCKII), rhoA, and protein kinase C (PKC) γ proteins were evaluated in a rat model of SAH. SAH was induced by double injection of autologous blood into the cistern magna on days 0 and 3. KMUP-3 was administered (0.3 mg/kg/day) by osmotic minipumps implanted subcutaneously (beginning day -3 in pretreatment group and at 1 h after the initiation of the first autologous blood injection in the treatment group). Neurological outcome was assessed by ambulation and placing/stepping reflex responses at 48 h after the second injection of autologous blood. Tissue morphology and protein expression were conducted on day 7 post-day 0 injection. Both KMUP-3 treatment regimens significantly improved neurological outcome and completely attenuated basilar artery narrowing as well as reduced the enhancement of ROCKII, rhoA, and PKCγ protein expression in rats subjected to SAH, compared with normal and untreated SAH rats. These results suggest that KMUP-3 may be a novel agent for the treatment of cerebral vasospasm following SAH.

The CHA2DS2-VASc score predicts chronic kidney disease among patients with atrial fibrillation.

BACKGROUND: It is unclear how the CHA2DS2-VASc score can predict subsequent chronic kidney disease (CKD) and end-stage renal disease (ESRD) among atrial fibrillation (AF) patients. METHODS: We identified incident AF patients without CKD between 2000 and 2013 from the National Health Insurance Research Database (NHIRD) of Taiwan and calculated the CHA2DS2-VASc score for each patient. Adjusted hazard ratio (HR) with 95% confidence interval (CI) was estimated from multivariate cause-specific Cox models to assess the risk of CKD and ESRD associated with the CHA2DS2-VASc score. RESULTS: A total of 8764 participants with AF who did not have CKD were included in the analysis. The mean age was 69.63 ± 13.48 years and 4800 (54.8%) were males. The adjusted HR of CKD displayed a stepwise increase with the increase in the CHA2DS2-VASc score. When compared with those with a CHA2DS2-VASc score of 0, the adjusted HRs of CKD were 1.57 (95% CI 1.09-2.26), 2.04 (95% CI 1.42-2.94), 2.48 (95% CI 1.70-3.62), 2.88 (95% CI 1.95-4.26), 3.29 (95% CI 2.18-4.95) and 4.00 (95% CI 2.61-6.13) for the AF patients with a CHA2DS2-VASc score of 1, 2, 3, 4, 5 and ≥ 6, respectively. Similarly, as the CHA2DS2-VASc score increased, the adjusted HR of ESRD showed a gradual increase. CONCLUSIONS: Patients with a higher CHA2DS2-VASc score were linked to a higher risk of CKD and ESRD in a dose-dependent effect, i.e. the incidence of CKD/ESRD increased with the increasing CHA2DS2-VASc score.

Low-grade astrocytoma associated with abscess formation: case report and literature review.

A rare case of low-grade astrocytoma associated with abscess formation occurred in a 52-year-old man presenting with Broca's aphasia. He underwent craniotomy and tumor removal under the impression of brain tumor with necrotic cystic change. Abscess accumulation within the intra-axial tumor was found intraoperatively. Literature related to brain abscess with brain tumor is reviewed, with an emphasis on abscesses with astrocytoma. We discuss the common brain tumors that are associated with abscess, pathogens that coexist with brain tumor, and the pathogeneses of coexisting brain abscess and tumor. It is very important to know how to differentiate between and diagnose a brain abscess and tumor, or brain abscess with tumor, preoperatively from clinical presentation and through the use of computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging or magnetic resonance spectroscopy.

FNIH-defined Sarcopenia Predicts Adverse Outcomes Among Community-Dwelling Older People in Taiwan: Results From I-Lan Longitudinal Aging Study.

Background: To evaluate the predictive validity of sarcopenia defined by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project among Asian older adults. Methods: Data of the I-Lan Longitudinal Aging Study were obtained for analysis. Overall, 1,839 community-dwelling people aged 50 years and older, capable of completing a 6-m walk, with life expectancy of more than 6 months, and not institutionalized at time of data collection were enrolled for study. Data for subjects aged 65 years and older were obtained for study. The outcome measures were all-cause mortality and a composite adverse outcome which includes hospitalizations, emergency department visits, institutionalization, and falls. Results: Data of 728 eligible elderly participants (73.4 ± 5.4 years; 52.9% males) were analyzed. The prevalence of FNIH-diagnosed sarcopenia was 9.5%: 11.9% males; 6.7% females. Participants having FNIH-defined sarcopenia were considerably older, frailer, more obese, with poorer physical performance than nonsarcopenic subjects (All p < .001); during mean follow-up of 32.9 ± 8.8 months, they also had 3.8 times higher risk of dying, independent of age, sex, multimorbidity, cognitive function, and nutritional status (hazard ratio = 3.8; 95% confidence interval = 1.26-11.45; p = .018). Moreover, sarcopenia defined by grip strength-BMI ratio (WeakBMI) showed stronger association with composite adverse outcomes than traditional handgrip strength (hazard ratio = 1.99; 95% confidence interval = 1.01-3.93; p = .047 vs hazard ratio = 1.80; 95% confidence interval = 0.89-3.62; p = .102 in fully-adjusted model). Conclusion: Among community-dwelling older people in Taiwan, participants with FNIH-defined sarcopenia had a significantly greater risk of all-cause mortality and composite falls, emergency department visits, institutionalization, and hospitalization.

Attenuation of experimental subarachnoid hemorrhage-induced increases in circulating intercellular adhesion molecule-1 and cerebral vasospasm by the endothelin-converting enzyme inhibitor CGS 26303.

OBJECT: Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important mediators of inflammation, and their levels are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The investigators previously found that CGS 26303 is effective in preventing and reversing arterial narrowing in a rabbit model of SAH. The purpose of the present study was to examine whether levels of adhesion molecules are altered after treatment with CGS 26303 in this animal model. METHODS: New Zealand White rabbits were each injected with 3 ml of autologous blood in the cisterna magna, and intravenous treatment with CGS 26303 (30 mg/kg) was initiated 1 hour later. The compound was subsequently administered at 12, 24, and 36 hours post-SAH. Blood samples were collected at 48 hours post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. After the rabbits had been killed by perfusion-fixation, the basilar arteries (BAs) were removed and sliced, and their cross-sectional areas were measured. Treatment with CGS 26303 attenuated arterial narrowing after SAH. Morphologically, corrugation of the internal elastic lamina of BAs was prominently observed in the SAH only and vehicle-treated SAH groups, but not in the CGS 26303-treated SAH group or in healthy controls. There were no significant differences in the levels of VCAM-1 among the four groups. The levels of E-selectin were increased in all animals subjected to SAH (those in the SAH only, SAH plus vehicle, and SAH plus CGS 26303 groups) compared with healthy controls (no SAH); however, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and treatment with CGS 26303 reduced ICAM-1 to control levels following SAH. CONCLUSIONS: These results show that ICAM-1 may play a role in mediating SAH-induced vasospasm and that a reduction of ICAM-1 levels after SAH may partly contribute to the antispastic effect of CGS 26303.

Analysis of surgically treated intraspinal tumors in southern Taiwan.

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988-1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), meningiomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41-50 years and 61-70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64-86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer).

Impact of living arrangements on clinical outcomes among older patients with dementia or cognitive impairment admitted to the geriatric evaluation and management unit in Taiwan.

AIM: To evaluate the impact of living arrangements on mortality and functional decline among older patients with dementia or cognitive impairment after discharge from a geriatric evaluation and management unit (GEMU) in Taiwan. METHODS: The present retrospective cohort study used data from the Veteran Affairs Comprehensive Geriatric Assessment from January 2015 to May 2016 for analysis. Data of patients aged 65 years and older with dementia or cognitive impairment at admission to the GEMU of Taipei Veterans General Hospital during the study period were retried for study. The Veteran Affairs Comprehensive Geriatric Assessment included demographic characteristics, Clinical Frailty Scale, Braden Scale, St. Thomas's Risk Assessment Tool in Falling Elderly Inpatients Scale, Cumulative Illness Rating Scale for Geriatrics, Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, Geriatric Depression Scale-5 and Mini-Nutritional Assessment - Short Form, as well as common geriatric syndromes. All patients were categorized into the home care group and institutional care group based on their living arrangement before GEMU admissions. Six-month mortality and decline in Barthel Index were defined as adverse clinical outcomes. RESULTS: Overall, data of 395 patients were used for analysis. The baseline comparisons showed that the institutional care group was more likely to be unmarried, have lower education, lower risk of falls and less polypharmacy, but more likely to experience functional decline at follow up than the home care group. Multivariate logistic regression showed that male (OR 3.59, 95% CI 1.04-12.38, P = 0.043) and higher Cumulative Illness Rating Scale for Geriatrics score (OR 4.08, 95% CI 1.49-11.19, P = 0.006) were associated with mortality, whereas the institutional care group (OR 0.30, 95% 0.09-0.99, P = 0.048) and lower Braden Scale (OR 0.80, 95% CI 0.67-0.94, P = 0.008) were protective against mortality. However, the institutional care group was independently associated with functional decline during the follow-up period (OR 2.19, 95% CI 1.12-4.29, P = 0.022). CONCLUSIONS: Institutional care was associated with lower 6-month mortality risk for patients with dementia or cognitive impairment after discharge from the GEMU, but this group was more likely to experience functional decline. Further prospective study is required to clarify the clinical impact of living arrangements on long-term outcomes when people with dementia or cognitive impairment are admitted to acute hospitals. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 44-49.

Recurrent falls and its risk factors among older men living in the veterans retirement communities: A cross-sectional study.

AIM: To evaluate the prevalence of recurrent falls and their risk factors among older men living in the Veterans Homes in Taiwan. METHODS: This cross-sectional study enrolled 871 residents and all participants received the comprehensive geriatric assessment, including Barthel Index, Mini-Mental Status Examination (MMSE), Geriatric Depression Scale-5 questions (GDS-5), Mini-Nutrition Assessment Short Form (MNA-SF), the status of urinary incontinence, stool incontinence, polypharmacy, past history of falls, multimorbidity, and medication history. RESULTS: Overall, 871 subjects (mean age: 85.5±5.2years, all males) participated in this study, whereas 222(25.5%) of them had experienced falls in the past year, and 91 were recurrent fallers. Comparisons between non-fallers, single fallers and recurrent fallers disclosed that they were significantly different in the following characteristics: diabetes mellitus, chronic kidney disease, coronary artery disease, Charlson Comorbidity Index (CCI), Barthel Index, GDS-5, MNA-SF, polypharmacy, use of hypnotics, urinary incontinence, and stool incontinence (P for trend all <0.05). Multiple regression analysis identified that GDS-5 was significantly associated with single falls and recurrent falls (OR 1.256, 95% CI 1.094-1.441, P=0.001 for single fallers; OR 1.480, 95% CI 1.269-1.727, P<0.001 for recurrent fallers). Besides, urinary incontinence was the independently associated with recurrent fallers only (OR 2.369, 95% CI 1.449-3.817, P<0.001), but not single fallers. CONCLUSION: Urinary incontinence and depressive symptoms were independent associated factors for falls among older men living in the retirement communities. However, urinary incontinence was associated with recurrent falls, but not single falls. Intervention study is needed to reduce recurrent falls through management of urinary incontinence.

Association between using medications with anticholinergic properties and short-term cognitive decline among older men: A retrospective cohort study in Taiwan.

AIM: The use of anticholinergic drugs had been strongly linked to adverse health outcomes among older adults, especially in cognitive impairment or dementia. The present study aimed to evaluate the cognitive decline related to the use of anticholinergic drugs among older men living in the veterans' homes in Taiwan. METHODS: This retrospective cohort study was a substudy of The Longitudinal Older Veterans study. A total of 274 residents living in four Taiwan veterans' homes and receiving two consecutive Mini-Mental State Examinations within the interval of 6 months from January 2012 to December 2014 were enrolled in the present study. The medication lists for all participants were reviewed by the same physician, and the anticholinergic properties of the individual medications were evaluated by using the Anticholinergic Cognitive Burden scale. Cognitive decline was defined as the decrease of Mini-Mental State Examinations scores during the study period. RESULTS: Overall, 139 persons (50.7%) had exposure to anticholinergic drugs at baseline (designated as AC[+]), and the most frequently used anticholinergic drugs were cardiovascular drugs (48.2%), antipsychotics (21.6%), theophylline (20.1%), antidepressants (12.2%), gastrointestinal drugs (11.5%) and antihistamines (8.6%). After adjusting for covariates, AC(+) participants had a significantly higher risk for short-term cognitive decline (OR 2.69, 95% CI 1.36-5.31). After excluding 30 participants using antipsychotics, non-antipsychotics AC(+)participants still had a significantly higher risk for short-term cognitive decline (OR 2.24, 95% CI 1.26-3.99). CONCLUSIONS: Exposure to anticholinergic drugs significantly increased the risk for short-term cognitive decline among older men, and the adverse effects remained similar when antipsychotics were excluded for analysis. A further intervention study is required to evaluate whether reducing anticholinergic burden might improve cognitive function among older adults. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 57-64.

Urinary Incontinence and Its Association with Frailty Among Men Aged 80 Years or Older in Taiwan: A Cross-Sectional Study.

AIMS: To evaluate the prevalence of urinary incontinence (UI) and its association with frailty among men aged 80 years and older in Taiwan. METHODS: Residents living in four veterans retirement communities were invited for study and 440 men aged 80 years and older were enrolled. Comprehensive geriatric assessment was performed for them, which composed of Clinical Frailty Scale, Northern Health and Social Care Trust (HSC)-Continence Assessment Form, Charlson's Comorbidity Index (CCI), Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-5 (GDS-5), and Mini-Nutritional Assessment-Short Form (MNA-SF). RESULTS: In this study, the overall prevalence of UI was 19.1% (mostly urgency incontinence and functional incontinence). Univariate analyses were performed to evaluate the associations between UI and other variables. Frailty was more common among subjects with UI than those without (60.7% vs 32.3%, p < 0.001). Besides, subjects with UI had more comorbidity (CCI: 1.40 ± 1.15 vs 0.89 ± 0.89, p < 0.001), poorer physical function (BI: 65.77 ± 33.39 vs 84.12 ± 24.08, p < 0.001; IADL: 3.46 ± 2.64 vs 4.41 ± 2.25, p = 0.003), more depressive symptoms (GDS-5: 1.83 ± 1.78 vs 1.18 ± 1.36, p = 0.02), poorer cognitive function (MMSE: 16.57 ± 7.65 vs 19.37 ± 6.82, p = 0.001), poorer nutritional status (MNA-SF: 10.0 ± 03.03 vs 11.23 ± 2.24, p = 0.001), more polypharmacy (66.7% vs 45.2%, p < 0.001) and higher chance of stool incontinence (22.6% vs 1.7%, p < 0.001). Multivariate logistic regression showed that UI was independently associated with frailty, (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2-3.6; p = 0.012), stool incontinence (OR = 14.4; 95% CI 5.2-39.7; p < 0.001) and depressive symptoms (OR = 1.30; 95% CI 1.10-1.54; p = 0.002). CONCLUSIONS: About one fifth of study subjects had UI (mostly urgency and functional incontinence type), which was significantly associated with frailty, stool incontinence and depressive symptoms. Further study is needed to evaluate the possibilities of reversing these geriatric syndromes by an integrated intervention program.

17beta-estradiol inhibits endothelin-1 production and attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.

Though cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) has been recognized for over half a century, it remains a major complication in patients with SAH. Clinical studies have shown that elevated levels of endothelin-1 (ET-1) are present in the cerebrospinal fluid of patients with SAH, suggesting that ET-1-mediated vasoconstriction contributes to vascular constriction after SAH. Administration of estrogen promotes vasodilation in humans and in experimental animals, in part by decreasing the production of ET-1. This study evaluated the influence of 17beta-estradiol (E2) on the production of ET-1 and cerebrovasospasm in an experimental SAH 2-hemorrhage model in rat. A 30-mm Silastic tube filled with E2 in corn oil (0.3 mg/ml) was subcutaneously implanted in male rats just before SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Plasma samples collected before death were assayed for ET-1. The protective effect of E2 in attenuating vasospasm achieved statistical significance when compared with the SAH only or SAH plus vehicle groups (P < 0.01). Concentrations of ET-1 were higher in the SAH only and SAH plus vehicle groups than in controls (P < 0.001). Serum levels of ET-1 in the SAH plus E2 and E2 only groups were significantly lower than those in the SAH only and SAH plus vehicle groups (P < 0.001). There was no significant difference between ET-1 levels in the healthy control and SAH plus E2 groups. A significant correlation was found between the cross-sectional areas of basilar artery and ET-1 levels (P < 0.001). The beneficial effect of E2 in attenuating SAH-induced vasospasm may be due in part to decreasing ET-1 production after SAH. The role of E2 in the treatment of cerebral vasospasm after SAH is promising and is worthy of further investigation.

Prevention and reversal of vasospasm and ultrastructural changes in basilar artery by continuous infusion of CGS 35066 following subarachnoid hemorrhage.

Endothelin-1, a potent vasoconstrictive peptide, has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). The goal of this study was to evaluate the effect of continuous intravenous infusion of a highly selective endothelin-converting enzyme-1 inhibitor, CGS 35066, on the prevention and reversal of cerebral vasospasm following SAH. New Zealand white rabbits were subjected to SAH by injecting autologous arterial blood into the cisterna magna. Infusion of CGS 35066 at dosages of 1, 3, or 10 mg/kg/ day was initiated either 1 hr and 24 hrs later in the prevention and reversal protocols, respectively. Animals were sacrificed by perfusion-fixation 48 hrs after SAH induction. The cross-sectional areas of basilar arteries were measured using computer-assisted videomicroscopy. Ultrastructural changes in basilar arteries were determined using electron microscopy. CGS 35066 significantly prevented and reversed the arterial narrowing after SAH in all three groups. The mean cross-sectional areas of arteries from animals in both the prevention and reversal protocol groups that received 10 mg/kg/day of CGS 35066 did not differ significantly from those of the healthy controls. Histological studies of the basilar artery in the 10 mg/kg/day treatment group did not show pathomorphological changes, such as corrugation of the endothelium seen at 2 days after SAH induction or vacuole formation in the endothelial cells noted in the vehicle-treated SAH group. These findings suggest that CGS 35066 is a promising therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH. It also prevents the pathological changes in vascular walls due to SAH.