Rapid tolerance against focal cerebral ischemia induced by isoflurane anesthesia is attenuated by adenosine A1 receptor antagonist in rats

The brief anesthesia with isoflurane induces rapid tolerance against focal cerebral ischemia in rats and aden-osine A1 receptor antagonist, DPCPX, attenuates the beneficial effect of isoflurane preconditioning.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non–heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non–heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non–heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.(Ann Thorac Surg 1997;63:1664–8)     

缺血预处理对缺血-再灌注硬化肝脏P-选择素表达的影响及保护作用

目的 :探讨缺血预处理 (IPC)对肝硬化肝脏缺血再灌注 (I R)损伤的保护作用以及 IPC对 P 选择素表达的影响和作用。方法 :2 4只雄性肝硬化 SD大鼠 ,随机分为 3组 ,每组 8只 :假手术组 (SO组 ) ,缺血再灌注组 (I R组 ) ,缺血预处理组 (IPC组 )。用高效液相色谱法测定肝组织三磷酸腺苷 (ATP)、二磷酸腺苷(ADP)、一磷酸腺苷 (AMP)并计算能荷 (EC) ,用全自动生化仪测定血清丙氨酸转氨酶 (AL T)、天冬氨酸转氨酶 (AST)、乳酸脱氢酶 (L DH) ,记录肝脏胆汁分泌量 ,用链霉菌抗生物素蛋白过氧化酶 (SP)法免疫组织化学染色检测肝组织 P 选择素蛋白表达 ,并计算肝组织中性粒细胞浸润数和丙二醛含量 (TBA法 )。结果 :再灌注12 0分钟后 ,IPC组 ATP含量和 EC水平明显高于 I R组 ,AL T、AST、L DH释放受到明显抑制 (P均 <0 .0 0 1) ,肝组织胆汁分泌量明显多于 I R组 (P<0 .0 1) ,肝组织中性粒细胞浸润数受到抑制 (P<0 .0 5 ) ,丙二醛产生明显减少 (P<0 .0 0 1)。与 I R组比较 ,IPC组肝细胞 P选择素蛋白表达受到明显抑制 (P<0 .0 5 )。结论 :缺血预处理通过抑制肝组织 P选择素的表达 ,减少中性粒细胞黏附浸润 ,从而减轻肝脏缺血再灌注损伤程度 ,保护肝功能     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

下肢缺血预处理对未成熟心肌的保护作用及其机制

目的　探讨下肢缺血预处理对未成熟心肌保护作用的机制。方法　采用双下肢缺血预处理 (DLIP)大白兔Langendorff离体心脏灌注模型。分为 4组 ,每组大白兔 6只 :E1组 ,动物麻醉后反复 3次阻断双下肢血流 5min ,松开 5min ,建立模型 ,灌注 15min转为工作心 15min ,全心停灌 45min ,恢复灌注 15min改为工作心 3 0min ;E2组 ,双下肢缺血预处理前静脉注射超氧化物歧化酶至双下肢缺血预处理完毕 ,重复E1组方法 ;E3组 ,静脉注射蛋白激酶C(PKC)阻滞剂多粘菌素B(PMB) ,时间 10min ,重复E1组方法 ;E4组 ,静脉注射ATP敏感性钾通道 (mitoKATP)阻滞剂(5 HD) ,时间 10min ,重复E1组方法。以左室功能恢复、心肌含水量、血清肌酸激酶 (CK )和乳酸脱氢酶 (LDH)漏出率、心肌组织ATP和丙二醛 (MDA)含量、超氧化物歧化酶 (SOD)活性、心肌细胞内Ca2 含量、心肌线粒体钙依赖性ATP酶 (Ca2 ATPase)活性及其Ca2 含量、心肌线粒体合成ATP能力 [ATP] m、超氧阴离子自由基 (O2 -)作为观察指标。结果　E1组左心室功能恢复优于其他各组 (P <0 .0 5 ) ,心肌ATP含量、SOD活性、Ca2 ATPase活性、[ATP] m 均优于其他各组 (P <0 .0 1) ,心肌含水量低于其他各组 (P <0 .0 5 ) ,MDA含量、CK、LDH漏出率、心肌细胞内Ca2 含量、心肌     

阿片受体在异氟醚延迟预处理减轻兔心肌缺血再灌注损伤中的作用

Objective To investigate the role of opioid receptors in the protective effects of isoflurane-induced delayed preconditioning against myocardial ischemia-reperfusion (I/R) injury in rabbits. Methods Forty male New Zealand white rabbits weighing 2.0-2.5 kg were randomly assigned into 4 groups ( n = 10 each) : group I sham operation (S); group II I/R; group Ⅲ isoflurane + I/R (Iso) and group IV Iso + naloxone + I/R (Nal). Myocardial I/R was induced by 40 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 120 min reperfusion. In group Ⅲ (Iso) 2% isoflurane in 100% O2 was inhaled for 2 h and I/R was produced 24 h later. In group IV (Nal) naloxone 6 mg/kg was given iv 10 min before 2 h of 2% isoflurane inhalation and I/R was produced 24 h later. At the end of 120 min reperfusion, infarct size (IS) and area at risk (AAR) were determined by Evan's blue and TTC staining. Myocardial ultrastructure was examined by electron microscopy. The phosphorylated p38MAPK protein expression in myocardium was determined by Western blot. Results The IS was significantly smaller in group Iso ( Ⅲ ) ( 19.7% ± 2.8%) than in I/R group ( II ) (37.8% ±1.7%) (P<0.05). The phosphorylated p38MAPK protein expression in myocardium was significantly lower in group Iso than in group I/R. Microscopic examination showed less myocardial damage in Iso group than in group I/R. The protective effects of delayed preconditioning by isoflurane was prevented by naloxone pretreatment. ConclusionOpioid receptors may be involved in the protective effects of delayed preconditioning by isoflurane against myocardial I/R injury.     

七氟醚预处理对体外循环冠状动脉旁路移植术病人围术期心肌的保护作用

目的探讨七氟醚预处理对体外循环(CPB)下冠状动脉旁路移植术(CABG)病人心肌的保护作用。方法择期CPB下CABG病人40例,ASAⅡ级或Ⅲ级,随机分为2组(n=20):七氟醚组(S组)或异丙酚组(P组)。麻醉维持:P组靶控输注异丙酚,血浆靶浓度2～3μg/L,静脉输注芬太尼2～3μg·kg~(-1)·h~(-1);S组夹闭主动脉前,吸入0.5%～2%七氟醚,静脉输注芬太尼2～3μg·kg~(-1)·h~(-1),夹闭主动脉后靶控输注异丙酚,血浆靶浓度2～3μg/L,静脉输注芬太尼2～3μg·kg~(-1)·h~(-1)。于切皮前即刻、CPB前即刻、CPB后即刻、回ICU后即刻、6、12h记录心率(HR)、平均动脉压(MAP)、肺动脉楔压(PCWP)、中心静脉压(CVP)、心脏指数(CI)、体循环血管阻力指数(SVRI)。于麻醉诱导前、回ICU后即刻、6、12、24h采集静脉血,测定血清心肌肌钙蛋白I(cTnI)浓度。记录术后不良事件的发生情况。结果2组各时点MAP、PCWP、CVP、HR和SVRI比较差异无统计学意义(P>0.05);与切皮前即刻和P组比较,S组回ICU后各时点CI升高(P<0.05)。与P组比较,S组回ICU后各时点cTnI浓度降低(P<0.05)。2组病人术后均无死亡;2组心肌梗塞、房颤和心肌缺血的发生率差异无统计学意义(P>0.05);S组cTnI浓度>2ng/ml的发生率低于P组(P<0.05)。结论七氟醚预处理对体外循环下冠状动脉旁路移植术病人围术期心肌具有一定的保护作用。     

Ischaemic episodes of less than 5 minutes produce preconditioning but not stunning in the isolated rat heart

The aim of the present study was to examine whether ischaemic episodes of less than 5 min could induce preconditioning or stunning in the isolated rat heart. Hearts were subjected to total global ischaemia of 1, 2 and 4 min followed by 10 min of reperfusion before an 18-min main ischaemic period and 30 min of reperfusion. The effects on physiology, purine metabolism and anaerobic glycolysis were compared with a control group subjected to the main ischaemia only. The brief ischaemic episodes did not produce stunning based on the recovery of left ventricular developed pressure (LVDP) and heart rate (HR) product during the first reperfusion. Preconditioning of 11–14% increased recovery of LVDP x HR during the second reperfusion was observed in the 1- and 4-min group. In the 2-min group a low repayment of flow debt during the first reperfusion was associated with a slightly reduced recovery of LVDP x HR compared to the other preconditioned groups during the second reperfusion. Only in the 4-min group was preconditioning associated with fewer breakdown products of the purine nucleotide pool (adenosine) and anaerobic glycolysis (lactate) in both tissue and effluate after the main ischaemia. Preconditioning (reflected in recovery of function) could be produced with ischaemic episodes of less than 5 min that did not produce stunning. Thus, stunning is probably not the primary cause of preconditioning.     

心率变异性在反映心脏自主神经损伤和重构中的应用

缺血预适应和急性心肌梗死恢复期都会出现心脏自主神经的变化,心率变异性（HRV）是无创测量心自主神经活动的重要方法.研究自主神经的变化能为疾病机理和临床用药研究提供理论基础,所以监测预适应和心梗后的HRV有着重要意义.本文综述了预适应和心梗恢复期在HRV上的体现,并将HRV的变化与生理生化证据相联系,分析了缺血预适应对自主神经的保护作用和心梗后用HRV检测自主神经恢复的可行性.同时还对心率变异性今后的研究方向做了展望.