Changes in the cardiac glutathione status after ischemia and reperfusion

Summary In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.This study was supported by a grant from Ministero Pubblica Istruzione and CNR Rome (no 8202331.56).     

Therapeutic induction of angiogenesis by direct myocardial administration of an adenovirus vector encoding human hepatocyte growth factor gene and its safety

After the study in vitro and in rats, we assessed further the effects and safety of local angiogen therapy using intramyocardial delivery of an adenovirus carrying hepatocyte growth factor gene (Ad-HGF) in a canine ischemia model. The angiogenic activity of Ad-HGF was evaluated from three aspects. First, the augmentation of collateral vessel development was assessed by angiography 30 d after surgery. The results showed that the density of collateral vessels in treated group was higher than that of control group. Secondly, infarct size was evaluated by TTC staining and image analysis. The results showed that the infarct size of treated group was smaller than that of control group. Thirdly, the myocardial regional blood flow was determined by the method of colored microspheres. The results showed that the blood flow recovered to the level before ligation in treated group, but that of the control group was lower than normal level. In addition, during the study of chronic toxicity, we tested the anti-adenovirus antibodies by neutralization method. The antibodies yielded after the fourth injection decreased slowly from peak level and disappeared 12 weeks after drug withdrawal. Overall, Ad-HGF can promote angiogenesis in ischemic myocardium and reduce infarct size. So this method may be considered as a therapeutic angiogenesis induction strategy for ischemic disease including myocardial infarction and peripheral artery disease. At the same time, Ad-HGF could induce the yield of anti-adenovirus antibodies to neutralize adenovirus, which may be the mechanism of adenovirus clearance.     

ST/HR slope 和功率踏车的慢性心肌缺血诊断系统的设计

针对传统的运用心电试验法诊断慢性心肌缺血时存在的一些缺陷:受试人员做运动试验时对于心电信号的干扰大、运动平板的适用人群有一定的限制、ST段压低的诊断指标敏感性和特异性都不高,设计了基于ST/HR slope诊断指标、功率踏车为运动试验装置的慢性心肌缺血诊断系统.ST/HR slope诊断指标通过计算机程序自动计算获得,免去了人工计算的繁琐与较大的误差;功率踏车能够有效的填补运动平板的应用空缺,降低运动时对心电采集的干扰.经过实验验证,证明该系统与传统系统相比较具有明显的优势,能够为运动心电试验法提供更高的诊断敏感性(93.8%)和特异性(94.5%).     

NMR Study of Damage on Isolated Perfused Rat Heart Exposed to Ischemia and Hypoxia

IntroductionMyocardial ischemia is the most common andprimary cause of myocardium damage. A rapidrestoration of the heartblood supply after injury isvery important for retaining its function.However,after a certain period of time,resumingthe blood supply may aggravate the damage to thecardiac muscle. Therefore,the mechanisms ofmyocardial ischemia and reperfusion damage mustbe studied to provide important data to reduce orprevent reperfusion damage in clinical treatmentofischemic heart diseases…     

双(7)他克林对大鼠海马缺血性损伤的保护作用

目的:研究双(7)他克林对大鼠缺血性脑损伤中海马神经元损伤的作用.方法:永久性结扎大鼠双侧颈总动脉建立老年性痴呆模型,手术动物随机分成2组,手术7 d后分别给以双(7)他克林和生理盐水灌胃,给药7d后灌注固定处死动物,取海马组织,常规脱水包埋,连续切片.分别进行常规HE染色、凋亡检测、PCNA及GFAP免疫组织化学染色...     

蒺藜总皂苷抗冠脉结扎诱导大鼠急性心肌缺血作用的研究

本实验通过建立大鼠冠状动脉结扎急性心肌缺血模型，观察蒺藜总皂苷抗急性心肌缺血的保护作用,结果发现蒺藜总皂苷可通过显著降低大鼠急性心肌缺血心电图ST段绝对值，升高血清中SOD，增强清除自由基的能力，降低血清中MDA含量，减少心肌梗死面积，进而对缺血心肌起到保护作用．     

高血压患者的无症状性心肌缺血及培哚普利治疗的影响

目的：探讨原发性高血压患者的无症状性心肌缺血（SMI）发生率和发作规律,研究培哚普利降压治疗对SMI的影响。方法：172例高血压患者和34例健康人均作动态心电图,采用1×1×1规则判定SMI发作。选30例有SMI发作但无ACEI禁忌症的高血压患者,服培哚普利4mg qd半年,1月、2月、4月、6月末作动态心电图复查。结果：172例高血压患者中60例共出现101次SMI发作,发生率34.9%,健康对照组无SMI,两组有极显著的差异（p〈0.001）。高血压患者的SMI发作以上午6：00至9：00最多,与其他时段比较有显著性差异（p〈0.05）。培哚普利治疗后血压明显降低,1个月后与治疗前比较有显著性差异（p〈0.05-0.01）,治疗2个月后SMI发作次数初显减少（p〈0.05）,而SMI发作的明显变化包括例数、次数的明显减少（p〈0.01）,迟至4月后才出现。心肌缺血总负荷在治疗4月后与治疗前比较有非常显著的降低（25.43±5.81mm.min,58.28±14.52mm.min,p〈0.01）。结论：高血压患者可出现SMI,培哚普利长期治疗有助于控制SMI发作。     

木芙蓉叶有效组分对大鼠肾缺血再灌注损伤的保护作用

为了探讨木芙蓉叶有效组分 (MFR)对大鼠肾缺血再灌注损伤中的作用 ,采用大鼠肾缺血再灌注模型 ,木芙蓉叶有效组分灌胃给药 ,观察血清尿素氮 (BUN)、肌酐 (Scr)及肾组织病理变化 ,并检测白细胞介素 - 1(IL- 1 )的含量。结果再灌注 2 4 h后 ,治疗组血 BUN及 Scr明显降低 (P <0 .0 5 ) ;治疗组血液 IL- 1含量与非治疗组相比有显著性差异 (P <0 .0 5 ) ;而且治疗组肾组织病理损伤较非治疗组明显减轻。木芙蓉叶有效组分对肾缺血再灌注损伤有保护作用 ,其原因可能与抑制 IL- 1等的生成有关     

人硫氧还蛋白对脑缺血作用的CT灌注与SOD相关性的实验研究

目的研究人硫氧还蛋白(hTRX)对局灶性兔脑缺血/再灌注损伤后脑组织的保护作用,并探讨其清除氧自由基的生物学活性.方法采用线栓法制成一侧兔脑缺血/再灌注模型(栓塞6 h,再灌注18 h),将25只雄性新西兰白兔随机分成假手术组(Sham组,5只)、缺血/再灌注组(I/R组,10只)和缺血/再灌注 hTRX治疗组(I/R hTRX组,10只),I/R hTRX组给予hTRX(0.75 mg/kg体质量),Sham组、I/R组以等容积的生理盐水取代hTRX;分别于梗死后6 h及再灌注后18 h做CT灌注图像,观察脑梗死面积,计算出其所占同侧大脑半球面积的百分比(HLA%);检测脑组织匀浆中SOD,MDA含量.结果脑缺血/再灌注后,脑梗死范围显著,脑组织匀浆中SOD明显下降,MDA明显升高(与假手术组比较,P<0.01);而应用hTRX能显著减小脑梗死面积,降低MDA及升高SOD含量(与B组比较,P<0.01).结论重组hTRX对脑缺血/再灌注损伤有显著的治疗作用.     

Pharmacological attenuation of apoptosis in reoxygenated endothelial cells

BRX-235 (Iroxanadine), a novel drug developed by Biorex (Hungary), was previously characterized as a vasculoprotector against atherosclerosis, an activator of p38 kinase, and an enhancer of stress-responsive heat shock protein (Hsp) expression. The present data demonstrate that BRX-235 may improve survival of vascular endothelial cells (ECs) following ischemia/reperfusion stress. ECs cultured from human umbilical veins were exposed to hypoxia/reoxygenation to mimic ischemia/reperfusion. Caspase activation and apoptosis were monitored in the reoxygenated cells. Addition of BRX-235 (0.1–1 M) to culture medium prior to hypoxia or at start of reoxygenation significantly reduced the caspase-dependent apoptosis. The cytoprotection conferred by the pre-hypoxic drug administration was sensitive to quercetin and seems to be based on enhanced Hsp accumulation in stressed ECs. In the case of post-hypoxic drug administration, the cytoprotection was strongly inhibited by SB202190 and SB203580 and appears to be associated with enhanced p38 kinase activation in reoxygenated ECs.Received 12 May 2004; received after revision 7 September 2004; accepted 24 September 2004