Redox signaling triggers protection during the reperfusion rather than the ischemic phase of preconditioning

In ischemic preconditioning (IPC) brief ischemia/reperfusion renders the heart resistant to infarction from any subsequent ischemic insult. Protection results from binding of surface receptors by ligands released during the preconditioning ischemia. The downstream pathway involves redox signaling as IPC will not protect in the presence of a free radical scavenger. To determine when in the IPC protocol the redox signaling occurs, seven groups of isolated rabbit hearts were studied. All hearts underwent 30 min of coronary branch occlusion and 2 h of reperfusion. IPC groups were subjected to 5 min of regional ischemia followed by 10 min of reperfusion prior to the 30-min coronary occlusion. The Control group had only the 30-min occlusion and 2-h reperfusion. In the second group IPC preceded the index coronary occlusion. The third group was also preconditioned, but the free radical scavenger N-2-mercaptopropionyl glycine (MPG 300 microM) was infused during the 10-min reperfusion and therefore was present in the myocardium in the distribution of the snared coronary artery during the entire reperfusion phase and also during the subsequent 30-min ischemia. In another preconditioned group MPG was added to the perfusate before the preconditioning ischemia and therefore was present in the tissue only during the preconditioning ischemia and then was washed out during reperfusion. In the fifth group MPG was added to the perfusate for only the last 5 min of the preconditioning reperfusion and therefore was present in the tissue during the last minutes of the reperfusion phase and the 30 min of ischemia. In an additional group of IPC hearts MPG was infused for only the initial 5 min of the preconditioning reperfusion and then allowed to wash out so that the scavenger was present for only the first half of the reperfusion phase. Infarct and risk zone sizes were measured by triphenyltetrazolium staining and fluorescent microspheres, resp. IPC reduced infarct size from 31.3 +/- 2.7% of the ischemic zone in control hearts to only 8.4 +/- 1.9%. MPG completely blocked IPC's protection in the third (39.4 +/- 2.8%) and sixth (36.1 +/- 7.7%) groups but did not affect its protection in groups 4 (8.1 +/- 1.5%) or 5 (7.8 +/- 1.1%). When deoxygenated buffer was used during IPC's reperfusion phase in the seventh group of hearts, protection was lost and infarct size was increased over that seen in control hearts (74.5 +/- 9.0%). Hence redox signaling occurs during the reperfusion phase of IPC, and the critical component in that reperfusion phase appears to be molecular oxygen.     

Effects of Ginkgo biloba extract and preconditioning on the diabetic rat myocardium

Summary Effects of preconditioning and Ginkgo biloba extract (EGb 761) were studied in isolated non-diabetic and diabetic ischaemic and re-perfused rat hearts. Hearts were randomly divided into five groups in both the age-matched non-diabetic and the 8-week streptozotocin-induced diabetic groups: Group I, hearts were subjected to 30 min of global ischaemia followed by 30 min of re-perfusion; Group II, one cycle of preconditioning consisting of 5 min ischaemia and 10 min re-perfusion before the induction of 30 min of ischaemia and 30 min of re-perfusion; Group III, two cycles of preconditioning; Group IV, three cycles; and Group V, four cycles before the onset of 30 min ischaemia followed by 30 min of re-perfusion. Four cycles of ischaemic preconditioning resulted in a reduction of arrhythmias in non-diabetic rats. Thus, in non-diabetics, the incidence of ventricular fibrillation and tachycardia fell from 92 % and 100 % (no preconditioning) to 33 % (p < 0.05) and 42 % (p < 0.05), respectively. Four cycles of preconditioning failed to reduce the incidence of re-perfusion arrhythmias in diabetic subjects. Preconditioning reduced the formation of oxygen free radicals measured by electron spin resonance spectroscopy, but the recovery of cardiac function was low in all non-diabetic and diabetic preconditioned groups. EGb 761 at 25 and 50 mg/kg improved cardiac function in non-preconditioned and preconditioned non-diabetic and diabetic hearts. During re-perfusion in the four-cycle preconditioned non-diabetic and diabetic groups, the amount of free radicals was reduced approximately by 50 and 70 % using 25 and 50 mg/kg of EGb 761, respectively. EGb 761 improved cardiac function after ischaemia in both non-preconditioned and preconditioned non-diabetic and diabetic rats. Our data suggest that diabetes could abolish the precondition-induced protection. [Diabetologia (1996) 39: 1255–1262] Received: 28 March 1996 and in revised form: 3 June 1996     

Absence of apparent cardioprotection following ischemic preconditioning in immature rabbit hearts

BACKGROUND: The cardioprotective effects of ischemic preconditioning (IPC) have been demonstrated in adult hearts of all species so far studied. Aims: To investigate whether IPC could protect immature rabbit hearts against ischemia-reperfusion injury in an isolated Langendorff-mode perfusion model. METHODS: Hearts from 18 rabbits aged 14-21 days were randomly divided into two groups (an IPC group and a control group). After isolated Langendorff-mode perfused hearts were equilibrated the IPC stimulus in the IPC group was 5 min global ischemia followed by 10 min reperfusion. Hearts in both groups were then made globally ischemic for 30 min (no perfusion), followed by 40 min reperfusion. Coronary flow (CF), heart rate (HR), left ventricular developed pressure (LVDP), and +/-dp/dt(max) were monitored at equilibration (baseline value) and then 5, 10, 20, 30 and 40 min after reperfusion. The values obtained after reperfusion were expressed as a percentage of their baseline value. Arrhythmia severity, myocardial enzymes in the coronary effluent, and myocardial energy metabolism were also determined. RESULTS: There were no statistical differences in postreperfusion CF, HR, LVDP and +/-dp/dt(max) between the two groups. Arrhythmia scores were also comparable between the two groups. The myocardial-specific isoenzyme of creatine kinase (CK-MB) leakage in the IPC group was increased, but not significantly different from that in the control group. At the end of reperfusion, the adenosine triphosphate (ATP) level in the myocardium in the IPC group was significantly lower than the level in the control group. CONCLUSIONS: This model of IPC was not able to protect juvenile rabbit hearts from ischemia-reperfusion injury. This study suggests that signal transduction pathways involved in triggering cardioprotective mechanisms may not be fully developed, or are not able to be invoked by the present model in juvenile rabbit.     

冠状动脉内支架置入术对有与无心肌梗死史患者QT离散度影响的比较

探讨和比较冠心病患者经过成功冠状动脉 (简称冠脉 )内支架置入术对有与无心肌梗死史的病人QT离散度(QTd)影响的程度 ,选择术前QTd≥ 60ms者 1 0 0例 ,根据有无心肌梗死病史分为两组 ,其中无心肌梗死组 62例 ,心肌梗死组 38例 ,于术前、后 72h分别做 1 2导联同步心电图进行测量QTd和计算校正QTd(QTcd)。在无心肌梗死组中 ,支架置入术后 ,QTd、QTcd明显缩短 (分别为 51± 1 9vs 72± 34ms,54± 2 4vs 81± 37ms;P <0 .0 5) ;而在心肌梗死史组中 ,术后QTd、QTcd上无显著变化 (分别为 70± 2 6vs74± 30ms ,80± 30vs82± 32ms;P >0 .0 5)。结论 :冠脉内支架置入术显著缩短无心肌梗死史冠心病患者的QTd和QTcd ,而对有心肌梗死冠心病患者的QTd和QTcd无影响     

A novel nutritional index and adverse outcomes in ischemic stroke: Results from the third China National Stroke Registry

Background and aimsFew studies have applied the triglyceride, cholesterol, body weight index (TCBI) in acute ischemic stroke (AIS). We investigated the association between the TCBI and adverse clinical outcomes in patients with AIS.Methods and resultsBased on the Third China National Stroke Registry (CNSR-III) data from August 2015 to March 2018, we evaluated the nutritional status of patients with AIS using the TCBI. Patients were categorized according to quartile levels of the TCBI. The main outcomes were poor functional outcomes and recurrent stroke at 1-year and secondary outcomes were adverse outcomes at 3 and 6 months after stroke onset. Poor functional outcomes consisted of all-cause mortality and major disabilities. Multivariate analyses with logistic or Cox regression analysis and restricted cubic splines determined the association between the TCBI and adverse outcomes. We included 9708 patients. At the 1-year follow-up, 1323 patients (13.6%) had died or experienced major disability. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the lowest quartile at 1-year were 1.47 (1.22–1.78) for poor functional outcomes, 1.46 (1.18–1.81) for major disability, and 1.34 (0.94–1.86) for all-cause mortality. Kaplan–Meier analysis demonstrated an inverse relationship between all-cause mortality and the TCBI (log-rank p < 0.05). An approximately L-shaped relationship between TCBI levels and poor functional outcomes and major disability was observed at 1-year.ConclusionThe novel TCBI was associated with short- and long-term adverse outcomes in AIS. Thus, it may be useful for predicting adverse outcomes in patients with AIS.     

超速起搏预适应的延迟保护与热休克蛋白70的表达

目的观察在超速心室起搏（ventricular overdrive pacing,VOP）预适应延迟保护阶段热休克蛋白70（HSP70）的表达水平。方法新西兰兔24只,随机分为3组,单纯结扎组,起搏组,起搏+放线菌素D组。制作超速起搏预适应和缺血/再灌注的动物模型,检测CK和CK-MB的变化,动态描记再灌注时心电图,免疫组织化染色检测HSP70抗原。结果缺血后起搏组心肌酶的水平在再灌注时均低于单纯结扎组和起搏+放线菌素D组（P<0.01）;单纯结扎组中在再灌注过程中共有5只发生心律失常,起搏+放线菌素组也有4只,而起搏组无心律失常发生。起搏组和单纯结扎组之间有显著性差别（P<0.05）。起搏组HSP70的阳性表达的程度明显高于其他两组。结论超速起搏预适应可以模拟缺血预适应,其延迟保护作用可能与HSP70表达增加密切相关。     

“预处理”策略对Ⅱ型糖尿病患者围术期心肌保护作用的研究进展

糖尿病是心血管疾患的独立危险因素,糖尿病患者发生急性心肌梗死后的病死率明显升高.缺血预处理（IPC）、缺血后处理（IPOST）、远端肢体/组织预处理（RIC）以及麻醉药物预处理（APC）等“预处理”策略,已被证明在非糖尿病患者能够发挥明显的心肌保护作用,近年有研究认为,在Ⅱ型糖尿病患者其心肌保护作用被减弱或者消失.现就“预处理”技术对Ⅱ型糖尿病患者缺血性心肌损害的保护作用及其机制的研究进展予以综述.     

硫酸锌预处理对大鼠心脏缺血/再灌注损伤心肌超微结构的影响

目的观察硫酸锌预处理对成年大鼠缺血再灌注损伤心肌的超微结构影响。方法将40只雄性SD大鼠随机分成4组（n=10）,即正常组（N组）、缺血/再灌注组（C组）、硫酸锌预处理组（Zn组）、缺血预处理组（IPC组）。建立SD大鼠缺血再灌注损伤模型,用透射电子显微镜观察心肌组织的超微结构,并进行线粒体评分。结果 Zn组、IPC组、N组超微结构损伤程度及线粒体评分低于C组（P〈0.05）。Zn组、IPC组和N组心肌超微结构损伤及线粒体评分差异无统计学意义（P=1.00）。结论缺血/再灌注可对心肌细胞超微结构造成严重损伤,硫酸锌预处理和缺血预处理均可减轻缺血再灌注所致的心肌细胞超微结构损伤,由此可推测硫酸锌预处理可以产生心肌保护作用。     

CT灌注技术在缺血性脑血管病血流重建手术中的应用研究

目的 探讨CT灌注在缺血性脑血管病血流重建手术中的应用价值以及如何进一步提高其检查结果的准确性和可靠性.方法 采用西门子sensation64螺旋CT,运用本研究总结出来的感兴趣区绘制办法,对2组实施血流重建手术的缺血性脑血管病患者在手术前后进行CT灌注检查,并采用本研究所归纳的CT灌注参数评价方法进行结果评价,再对手术前后的结果进行统计学分析.结果 每个患者均进行了合理准确的感兴趣区绘制,并半定量测定了手术前后的CT灌注参数.手术前2组病例责任血管供血区域血流灌注均降低,手术后均较术前改善,与患者临床症状体征的改变相符.结论 CT灌注对局部脑血流的评价结果是缺血性脑血管病血流重建前的重要手术指证;CT灌注对于缺血性脑血管病血流重建后的疗效评估很有价值;正确的绘制感兴趣区（ROI）对于保证CT灌注的准确性非常重要;计算患侧/健侧的相对值是评估CT灌注参数的主要方法.     

人巨细胞病毒感染与急性缺血性脑卒中的关系

目的 探讨人巨细胞病毒（HCMV）感染与急性缺血性脑卒中（CIS）的关系.方法 以急性CIS患者为研究对象,以体检者为对照.采用荧光定量PCR法检测HCMV水平,单因素分析比较2组性别、年龄、血压、血糖、血脂、吸烟、饮酒、体重指数及HCMV的差别;后采用Logistic回归分析探讨HCMV与CIS发病的关系.结果 ①试验组高血压、糖尿病、高胆固醇血症及高甘油三酯血症患者比例显著高于对照组,差异均有统计学意义（均P＜0.05）;②试验组HCMV阳性率（51.25％）显著高于对照组（23.75％）,差异有统计学意义（P＜0.01）;③Logistic 回归分析表明,HCMV是CIS发病的独立危险因素（95％可信区间=1.115～1.625,P=0.004）.结论 HCMV感染与CIS发病具有密切关系.