Protection by lloprost (stable analogue of prostacyclin) of endothelial damage due to chronic vasospasm in dogs: An electron microscope study

Abstract

The resolution of cerebral vasospasm and protection of endothelial damage by lloprost was evaluated with multicisternal injections. Sixteen adult mongrel dogs (18-20 kg) were assigned to one of three experimental groups. All animals received a total amount of 15 ml fresh unheparinized arterial blood via three injections into the cisterna magna. Selective vertebral angiography was performed on day 0 and subsequently blood injections were performed on the 2nd and 3rd days after the first injection. On the 7th day angiography was reperformed to determine the chronic vasospasm. The first group (5 dogs) was the control group and received intrathecal saline which was equal to the amount of saline in which lloprost was diluted. The second group (5 dogs) did not receive any treatment until the 7th day. The third group (6 dogs) received lloprost intrathecally (total 10 fig kg~1). In the first two groups angiographic vasospasm was prominent. For the second group intraarterial lloprost was given on the 7th day in order to evaluate its acute effect. However there was no evidence of resolution of vasospasm. In the third'group, resolution of vasospasm was verified on angiograms. Electron microscope studies of basilar arteries of the first two groups revealed degenerative changes of the endothelial cells which were separated from each other and the elastic lamina was irregularly arranged. In the intrathecal lloprost-treated group there was little thickening in the elastic lamina and the endothelial cells were almost normal in structure. These results can be considered as the evidence of the prophylactic effect of lloprost given by the intrathecal route in the prevention of chronic cerebral vasospasm. [Neurol Res 1995; 17: 301-306]     

Endothelium-dependent relaxation and vasospasm in the single-hemorrhage canine model

Abstract

We have investigated the relationship between angiographic vasospasm and the ability of spastic vessels to relax in response to agents which promote release of endothelium derived relaxing factor. Vasospasm was induced in dogs by the 'single hemorrhage' technique. Animals received a single intracisternal injection of blood, blood activated with thromboplastin or collagen, or inert material, and angiograms were obtained day 0 and day 7. Vasospasm was estimated by measuring the ratio of the diameter of the vessel before and after treatment. Rings of cerebral artery obtained from these animals were suspended in a standard organ- bath arrangement, contracted with prostaglandin F2(X and then treated with increasing doses of adenosine triphosphate or bradykinin, both of which cause relaxation by an endothelium-dependent process. The arteries from animals with moderate to severe vasospasm showed a response to bradykinin and adenosine- triphosphate which was reduced, absent or converted to a contraction, when compared with normal vessels. Vessels in which vasospasm was mild or absent relaxed as expected to these agents. The reduction in vessel diameter showed a highly significant correlation with the reduction in relaxation to bradykinin or adenosine-triphosphate. These results have demonstrated that impairment of endothelium-dependent vasorelaxation correlates with the existence of vasospasm. [Neurol Res 1996; 18: 553-558]     

Clinical characteristics and outcomes of neurogenic stress cadiomyopathy in aneurysmal subarachnoid hemorrhage

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is an often devastating form of stroke. Aside from the initial hemorrhage, cardiac complications can occur resulting in neurogenic stress cardiomyopathy (NCM), leading to impaired cardiac function. We investigated whether aSAH patients with NCM had poorer long term functional outcomes than patients without NCM. Mortality, vasospasm, and delayed ischemic complications were also evaluated.

Methods

A retrospective study of all patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) from January 2006 to June 2011 (n = 299) was conducted. Those patients who underwent an echocardiogram were identified (n = 120) and were assigned to the NCM (n = 49) category based on echocardiographic findings defined by a depressed ejection fraction (EF%) along with a regional wall motion abnormality (RWMA) in a non-vascular pattern. Primary outcome measures included in-hospital mortality and functional outcomes as measured by the Modified Barthel Index (mBI) at 3 months and one year. Secondary analysis determined if there was an association between NCM, cerebral vasospasm and delayed cerebral ischemia.

Results

16% of aSAH patients developed NCM. Mortality was higher (p < .001) in the NCM group (n = 23[46.9%]) than in the non-CM group (n = 28[11.2%]). Patients with NCM had poorer functional outcomes as measured by the mBI at both 3 months (p = .002) and 12 months (p = .014). The Hunt–Hess score was predictive of functional outcome as measured by the mBI at both 3 months (p = .002) as well as at 1 year (p = .014). NCM was associated with both death (p = .047 CI, 1.012–7.288) and vasospasm (p = .008 CI, 1.34–6.66) after correction for Hunt–Hess grade. Tobacco use (p < .001) and a history of diabetes mellitus (p < .009) were also associated with vasospasm. NCM was associated with higher in-hospital mortality (p = .047) in multivariate analysis.

Conclusion

NCM is seen in a substantial number of aSAH patients and when present, it is associated with higher mortality and poorer long-term functional outcomes. This finding may guide further prospective studies in order to determine if early recognition of NCM as well as optimization of cardiac output would improve mortality.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛与血浆花生四烯酸代谢产物的关系

目的探讨动脉瘤性蛛网膜下腔出血(aSAH)病人血浆花生四烯酸代谢产物的含量与脑血管痉挛(CVS)发生、发展之间的关系。方法选取34例aSAH病人作为研究组,在aSAH后第1、3、7、14天抽取外周静脉血测定血栓素B2(TXB2)和6-酮-前列腺素F1α(6-Keto-PGF1α)的含量。另选取同时期健康成人6例作为对照组,进行对比研究。结果研究组发生CVS 23例,其中表现为迟发性缺血性神经功能障碍(DIND)的症状性CVS 10例,无症状性CVS(无DIND)13例。与对照组相比,研究组各时间点血TXB2含量均明显升高,而血6-Keto-PGF1α含量变化无显著性差异;与无CVS病人相比,CVS病人血TXB2含量在各时间点均明显升高,而血6-Keto-PGF1α含量仅在第7天时明显降低;与无DIND病人相比,DIND病人血6-Keto-PGF1α含量在第1、3、14天明显降低,而血TXB2含量仅在第3天时明显升高。结论 aSAH后CVS、DIND的发生、发展与血TXB2、6-Keto-PGF1α含量变化可能存在相关性。     

机械性脑血管痉挛与血管内皮细胞缺血瀑布级联效应的实验观察

目的：观察术中急性机械性脑血管痉挛．早期（2h）大脑中动脉（MCA）血管内皮细胞的反应。方法：6只猫，眶后入路，暴露右侧MCA，机械刺激30min，观察刺激后不同时段，血管直径的改变；高效液相色谱（HPLC）分析颞叶皮质间隙谷氨酸Glu浓度变化：镜下观察颞叶皮质形态学和MCA血管内皮细胞结构的改变。结果：机械性刺激MCA后．MCA直径缩小，为刺激前的68．78％。脑组织灌流指数下降到刺激前的42．59％。刺激结束后2h．MCA直径恢复正常。脑组织灌流量恢复到刺激前的61．87％。HPLC显示颞叶和枕叶脑组织间隙兴奋性氨基酸急剧升高．光镜下颞叶皮质神经元固缩．血管周围水肿。电镜观察发现，MCA经急性机械性刺激后早期（2h）MCA内皮细胞染色质聚集，凝聚成新月形小体。线粒体嵴模糊不清。结论：机械性刺激猫脑MCA诱发血管痉挛早期f2h）显示内皮细胞的缺血瀑布级联效应．与神经元细胞凋亡相呼应。但是其病理过程与蛛网膜下腔出血、脑卒中引发的血管内皮细胞的凋亡和血管痉挛不同。提示．颅脑手术或动物实验中机械性脑血管痉挛可能影响术后神经功能的康复。     

尼莫地平在治疗蛛网膜下腔出血后脑血管痉挛的临床疗效

目的：分析研究在对蛛网膜下腔出血后脑血管痉挛进行治疗时,尼莫地平的使用效果。方法以本院收治的100例该类患者为对象,等分为两组,观察组给予常规的神经营养以及止血和降低颅内压等常规治疗,试验组则在上述基础上微量泵入尼莫地平,剂量1 mg/h,连续使用14 d后更换为以3次/d为频率的30 mg尼莫地平片剂。治疗后首日、第3日、第7日及第14日,采用颅多普勒超声检测患者大脑动脉血流动力等情况,疗程结束后3个月进行随访,进行预后评分以统计疗效。结果试验组患者大脑动脉血流动力学指标以及随访所得之预后结果均好于观察组,对比差异具有统计学意义（P〈0.05）。结论蛛网膜下腔出血后脑血管痉挛患者应用尼莫地平可以起到更好的治疗效果,有助于患者预后的改善,缓解脑血管痉挛,改善脑供血,值得推广。     

Diagnosis of coronary vasospasm by detection of postischemic regional left ventricular delayed relaxation using echocardiographic evaluation with color kinesis

BACKGROUND: Coronary vasospasm has been diagnosed by invasive provocative procedures during coronary arteriography. It would be useful to have a reliable, noninvasive, and safe diagnostic method for coronary vasospasm. Regional left ventricular (LV) diastolic dysfunction may persist without systolic dysfunction after an episode of coronary vasospasm. Color kinesis (CK) has been recently developed to facilitate the echocardiographic evaluation of regional wall motion. HYPOTHESIS: Color kinesis may be useful for diagnosis of coronary vasospasm by detection of postischemic regional LV diastolic wall motion abnormality. METHODS: Fifty-one consecutive patients with the last chest symptom within 2 weeks (4 +/- 3 days) were studied echocardiographically. Regional fractional area change during the first 30% of LV filling time in percentage of the segmental end-diastolic area change (CK diastolic index) was used to identify diastolic endocardial motion asynchrony. RESULTS: After diagnostic coronary arteriography with spasm provocation, 26 patients were diagnosed with coronary spastic angina (CSA) and the other 25 with chest pain syndrome (CPS). Regional delayed relaxation (CK-diastolic index < or = 50%) or diastolic asynchrony had been observed in at least one region in 25 (96%) patients with CSA, whereas it had been noted in 2 (8%) patients with CPS. In 17 (65%) patients with CSA, it had been detected in multiple vascular territories, suggesting multivessel spasm. The diastolic asynchrony disappeared in CSA after a month of angina-free period. CONCLUSION: Analysis of CK images allows identification of regional LV delayed relaxation or diastolic asynchrony in patients with coronary vasospasm, differentiating them from patients with chest pain syndrome (sensitivity 96%, specificity 92%).     

法舒地尔动、静脉给药治疗颅内动脉瘤栓塞后脑血管痉挛的对比研究

目的探讨法舒地尔动脉推注(IAF)与静脉给药对脑动脉瘤栓塞后脑血管痉挛(CVS)的疗效对比并评估其安全性。方法介入栓塞治疗后出现脑血管痉挛39名患者,随机分成A、B二组。A组,改用静脉法舒地尔治疗,30 mg,3次/d;B组立即行动脉内注射盐酸法舒地尔(60 mg+生理盐水100 ml,60 min缓慢推注治疗),连续3 d,3 d后予常规静脉法舒地尔治疗。结果 B组IAF治疗后血管痉挛程度明显改善,第3 d、7 d、14 d的GCS评分均高于A组,3月后GOS评分明显高于A组。结论 IAF能安全有效地缓解蛛网膜下腔出血后脑血管痉挛的临床症状并改善预后。