NO和氧自由基在心肌缺血再灌注损伤中的协同作用——心肌缺血再灌注损伤产生的NO自由基的ESR研究

用低温电子自旋共振(ESR)技术检测到了大鼠心肌缺血再灌注过程产生的NO自由基与含铁蛋白结合的ESR信号 并且利用这一技术研究了大鼠心肌缺血再灌注损伤过程中NO和氧自由基的协同作用.结果发现,在缺血再灌注损伤的心肌中可同时检测到氧自由基和与血红蛋白β-亚基铁结合的NO自由基(β-NO复合物).在正常心肌中检测不到这两个信号,即使在灌注液中加入L-精氨酸也检测不到这两个信号.在缺血再灌注损伤的心肌中就可以检测的这两个信号了,而且随着在灌注液中加入L-精氨酸浓度的增加,这一信号也随之增加.在灌注液中加入NO合成酶抑制剂N~G-硝基精氨酸甲脂(NAME),这两个信号受到抑制.在灌注液中检测标志心肌损伤的乳酸脱氢酶(LDH)和肌酸激酶(CK)活性发现,在灌注液中加入低浓度的L-精氨酸(1mmol/L以下),对缺血再灌注心肌损伤有一定保护作用,但是,若加入高浓度L-精氨酸,则加重缺血再灌注心肌的损伤.加NAME对缺血再灌注心肌有明显保护作用.在灌注液中加入黄嘌吟/黄嘌吟氧化酶(X/XO)或Fe²⁺/H₂O₂,同时增加缺血再灌注心肌中的NO和氧自由基含量,并加重心肌的损伤.在灌注液中加入超氧化物歧化酶(SOD)和过氧化氢酶(CAT),同时减少缺血再灌注心肌中NO和氧自由基的含量,并减轻心肌的损伤.     

青藤碱抗大鼠肝脏缺血/再灌注损伤作用的机制探讨

目的:观察青藤碱时大鼠肝脏缺血再灌注损伤的影响,探讨其保护大鼠肝脏缺血再灌注损伤作用的机制.方法:通过建立大鼠全肝缺血再灌注损伤模型,应用硝酸酶还原法测定肝脏缺血再灌注后60min血清NO水平变化;测定再灌注60 min后肝组织内MDA和SOD含量变化;再灌注60min取肝组织完成肝组织显微结构的观察.结果:肝脏缺血再灌注损伤后血清NO水平降低;青藤碱能提高再灌注后血清NO水平,且能改善肝脏缺血再灌注损伤的微循环,减轻肝细胞内超微结构的损害程度.结论:青藤碱对大鼠肝脏缺血再灌注损伤有保护作用,其主要作用机制是清除氧自由基和改善微循环.     

离体缺血再灌注鼠心肌钙离子的变化

用液体闪烁计数法测定离体再灌注鼠心肌肌质网(SR)和线粒体(Mit)内 ⁴⁵Ca²⁺放射性强度(cpm),比较能量制剂ATP-MgCl₂,活性氧自由基清除剂SOD和钙阻滞剂Verapamil对离体缺血再灌注鼠心肌细胞SR和Mit钙离子浓度的影响.结果表明,SR内ATp-MgCl₂,SOD和Verapamil组 ⁴⁵Ca²⁺的cpm均高于对照组(P<0.0l或P<0.05),而Mit内均低于对照组(P<0.01).此三种药均能提高离体大鼠心肌细胞内SR ⁴⁵Ca²⁺和降低Mit ⁴⁵Ca²⁺积聚,从而保护了心肌细胞,防止缺血再灌注损伤.     

稀土La3+跨PC12细胞膜行为研究

使用AR-CM-M1C阳离子测定系统,发展Fura-2荧光测定技术,将其应用于测定细胞内游离稀土离子La³⁺,并以此研究了La³⁺跨PC12细胞（大鼠嗜铬细胞瘤细胞）膜的行为.结果表明：在模拟细胞内离子组分,pH=7.05的溶液中,测得La³⁺-Fura-2的表观解离常数为3.27×10^-11 mol·L^-1.对于PC12细胞,静息条件下La³⁺不能跨越细胞膜进入胞内.与钙离子通道相关的KCl和去甲肾上腺素均不能刺激稀土La³⁺过膜.用哇巴因（ouabain）使胞内Na⁺超载后,La³⁺可过膜进入细胞内,且过膜量与胞外La³⁺浓度和胞内Na⁺超载程度有一定的浓度依赖关系,提示La³⁺可以经由Na⁺／La³⁺交换机制过膜而进入细胞内.     

腺苷预处理对培养大鼠心肌细胞"缺血-再灌注"性膜损伤的影响

目的探讨腺苷预处理对缺血-再灌注心肌细胞膜损伤的保护作用.方法将培养5天的SD乳鼠心肌细胞随机分成4组正常组常规条件下(DMEM培养基及95% 空气+ 5% CO2 气体环境)培养50min;拟缺血/再灌注组先在缺糖缺氧条件下(无糖Eagle 培养基及95% N2+ 5% CO2 气体环境)培养30min,再恢复常规条件培养20min;拟缺血预处理组先缺糖缺氧培养5min,再复氧复糖培养5min,反复3次后按模拟缺血/再灌注组操作;腺苷预处理组用含腺苷(0.15g/L)培养液在常规条件下培养10min,再作拟缺血/再灌注组处理.扫描电镜下观察各组细胞的变化,并用胶体苯胺染色及Ridit分析法对PLA活性进行半定量.结果与正常组比较,模拟缺血/再灌注组细胞的质膜和线粒体的结构损伤严重,PLA活性显著性增强.而模拟缺血预处理和腺苷预处理组细胞质膜和线粒体损伤较轻,PLA活性显著低于拟缺血/再灌注组.结论腺苷预处理对"缺血-再灌注"损伤心肌的细胞膜有保护作用,其机制可能与腺苷直接或间接地抑制PLA活性,增强质膜的稳定性有关.     

Losartan和人参对实验性大鼠心肌缺血再灌注心肌细胞凋亡影响的比较研究

目的　研究Losartan和人参对缺血再灌注心肌细胞凋亡的影响 ,比较Losartan和人参对缺血再灌注心肌细胞损伤的保护作用。方法　结扎Wistar大鼠左冠状动脉前降支 ,建立大鼠缺血再灌注动物模型 ,采用末端标记原位细胞凋亡法检测心肌细胞凋亡 ,并利用光学显微镜进行细胞计数。结果　单纯缺血 再灌注组心肌细胞凋亡数较假手术组明显增多(37 5± 9 2 2 /视野vs 0 18± 0 0 91/视野 ,P <0 0 5 ) ,Losartan组和人参组心肌细胞凋亡数分别为 6 5 0± 3 5 9/视野和 8 74± 3 5 1/视野 ,较单纯缺血 再灌注组明显减少 (P <0 0 5 ) ,Losartan和人参两组间无明显区别 (P >0 0 5 )。结论　缺血再灌注可引起明显的心肌细胞凋亡 ,Losartan和人参对缺血再灌注心肌损伤具有相似的保护作用 ,均可明显减少缺血再灌注心肌细胞凋亡。     

血红素氧合酶-1参与心肌细胞延迟预适应

目的:探讨血红素氧合酶-1(HO-1)在心肌细胞缺血预适应(IPC)中的作用。方法:实验分5组:正常对照组(CN组)、缺血/再灌注组(I/R组)、缺血预适应+缺血/再灌注组(PC组)、ZnPP(HO-1抑制剂)+缺血预适应+缺血/再灌注组(ZP组)和Hemin(HO-1诱导剂)+缺血/再灌注组(HE组)。测定HO-1mRNA表达、心肌细胞存活率、胞内[Ca2+]i和细胞培养液中MDA含量等。结果:PC组和HE组HO-1mRNA表达量和细胞存活率显著高于I/R组,而MDA含量和胞内[Ca2+]i则皆显著低于I/R组,PC组各指标与ZP组间有显著性差异,与HE组66较未见显著性差异。结论:IPC可以诱导HO-1mRNA表达,对心肌细胞缺血/再灌注损伤产生延迟保护作用。     

异丙酚对离体大鼠心肌缺血、再灌注损伤后细胞凋亡及其机制研究

目的：观察异丙酚对离体大鼠心肌缺血/再灌注损伤的影响并从氧化应激和线粒体介导的凋亡方面探讨其作用机制。方法：应用Langendorff离体心脏灌注系统建立心肌缺血/再灌注损伤模型。40只SD大鼠随机分为正常对照组、缺血/再灌注模型（I/R）组、异丙酚15、30、60μmol.L-1组。除正常对照组外,各组分别平衡灌注20 min后,常温全心停灌25 min,再灌注30 min。Powerlab/8s仪记录各组平衡末、缺血前及再灌30 min时的各项心功能指标并测定冠脉流出液中乳酸脱氢酶（LDH）、肌酸激酶（CK）活性;检测心肌线粒体活力、膜肿胀度、锰超氧化物岐化酶（Mn-SOD）活性和丙二醛（MDA）含量;流式细胞仪检测心肌细胞凋亡;流式细胞术检测Bcl-2和Bax的表达,免疫组化法测定天冬氨酸特异的半胱氨酸蛋白酶（caspase）-3,9,8蛋白的表达。结果：与I/R组相比,异丙酚30、60μmol.L-1能明显改善缺血/再灌注后的心功能,减弱冠脉流出液中LDH、CK的活性（P〈0.05）;心肌线粒体活力有所恢复,膜肿胀度减轻,Mn-SOD活性升高,MDA生成明显减少（P〈0.05）,心肌细胞凋亡明显减少,Bcl-2表达上调,Bax表达下调,caspase-3,9阳性表达细胞数明显减少（P〈0.05）。结论：异丙酚明显减轻缺血/再灌注所致的心肌线粒体的过氧化损伤,抑制线粒体途径的凋亡,可能是其心肌保护作用机制之一。     

三尖杉酯碱诱导的HL-60细胞凋亡的钙调节

三尖杉酯碱 (harringtonine ,HT)是一种对急性粒细胞白血病、急性单核细胞白血病有良好疗效的抗癌药物 ,可在很宽的剂量范围内迅速诱导HL -6 0细胞凋亡 .细胞外钙离子螯合剂EGTA不抑制抗癌药物HT、喜树碱 (campothecin ,CAM )诱导的-细胞凋亡 ;而细胞内Ca ²⁺螯合剂BAPTA AM却可抑制该过程 .与此相一致 ,HT和CAM也不能诱导胞内Ca ²⁺已排空的HL -6 0细胞凋亡 ,说明HT ,CAM诱导的HL- 6 0细胞凋亡依赖于胞内Ca ²⁺但是HT ,CAM诱导HL -6 0细胞凋亡过程中胞内自由Ca ²⁺浓度变化不大 .利用视频反差增强显微术 (videoenhance mentcontrastmicroscopy ,VEC)研究了单个HL- 6 0细胞凋亡过程中胞内Ca ²⁺分布的动态变化 ,结果表明HT诱导HL -6 0细胞凋亡过程存在胞内Ca ²⁺由胞质向核的位移 .     

脉冲电场引起的红血球内钠离子浓度变化的研究

利用位移试剂和²³Na-NMR的方法研究脉冲电场对正常人红血球内Na⁺浓度的影响,实验结果给出在高强度电场作用下,细胞内Na⁺浓度增加,并且随脉冲强度的增加而增加,比指数关系还快.在低强度电场作用下,细胞内Na⁺浓度减少.乌苯苷能抑制细胞内Na⁺浓度的减少,抑制程度随乌苯苷浓度的增加而增强,从而证实了低强度的脉冲电场对Na⁺,K⁺-ATPase的激活作用,直接测定脉冲电场对红血球血影膜的Na⁺,K⁺-ATPase活性的影响,进一步证实了这一结果.并对在电场作用下细胞膜的通透性和电场对酶的激活作用及电场等外界物理信号是否能跨过细胞膜等进行了讨论.     

Effects of L-carnitine and its acetyl and propionyl esters on ATP and PCr levels of isolated rat hearts perfused without fatty acids and investigated by means of 31P-NMR spectroscopy

³¹P-NMR in vivo spectroscopy is a non-invasive and non-hazardous technique which investigates chemical composition and metabolism of living objects, for example by determining phosphocreatine (PCr) and ATP concentrations. In the present study we investigated the influence of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine on the energetic state of the Langendorff rat heart subjected to an ischemic period of 20 min followed by a reperfusion period of 60 min. To avoid an overlapping of the effects of fatty acids and glucose, the hearts were perfused with a Tyrode solution containing no fatty acids. Ischemia causes a rapid decrease in the PCr signal, followed by a decrease in the ATP signal after a prolonged period of ischemia. At the same time, a drastic increase in the P_i signal was observed. A partial recovery of the ATP and PCr signals was observed in the reperfusion period. With L-carnitine a markedly improved recovery of the high energy phosphates (e.g. increased PCr/P_i ratios) was found. With acetyl-L-carnitine this effect was enhanced in the first postischemic phase. It was followed, however, by a more rapid decrease in the PCr/P_i ratio in the late reperfusion period. The effect of propionyl-L-carnitine was not significantly improved in the first minutes of the reperfusion period, but during the whole reperfusion phase a stabilization of the PCr/P_i ratio was observed. Intracellular pH can be calculated from determination of the P_i-chemical shift. This shows that L-carnitine and its derivatives have a protective effect against intracellular pH decrease during ischemia. L-carnitine improves the energetic state of the heart, which leads to increased ischemia tolerance. Hearts under L-carnitine were able to tolerate up to four ischemia-reperfusion periods in succession, whereas the controls were not able to do so. These NMR results confirm the hypothesis that L-carnitine and its esters have a protective effect in the reperfusion period of the ischemic rat heart. This could be of importance for the treatment of ischemic cardiac diseases.     

Na+-H+ exchange inhibition at reperfusion is cardioprotective during myocardial ischemia-reperfusion; 31P NMR studies

To help resolve the controversy as to whether or not Na⁺-H⁺ exchange is functioning during reperfusion of the ischemic myocardium we assessed the effects of dimethylamiloride (DMA, an amiloride analogue possessing selectivity for inhibition of the Na⁺-H⁺ exchanger) on cardiac function and intracellular pH during ischemia-reperfusion. Studies were performed in the presence of bicarbonate (modified Krebs-Henseleit buffer) or in the nominal absence of bicarbonate (HEPES buffer) in order to determine if similar cardioprotection and effects on intracellular pH were observed in the presence and absence of bicarbonate dependent transport processes. Isovolumic rat hearts were perfused in the Langendorff mode at a constant pressure of 80 mm Hg and subjected to 28 min total global ischemia at 37°C. Intracellular pH was determined from the pH dependent shift of the inorganic phosphate peak in ³¹P nuclear magnetic resonance spectra. DMA (20 µM) was infused for either 2.5 min before ischemia, for the initial 5 min of reperfusion, or at both time intervals. DMA had no effect on the intracellular pH during ischemia. Intracellular pH returned to pre-ischemic levels within 2.5 min of reperfusion in bicarbonate buffer. This normalization of pH was slower in HEPES perfusate. In both bicarbonate and HEPES perfused hearts all drug dosing regimens caused a significant increase in the recovery of mechanical function after reperfusion and slowed the recovery of intracellular pH during reperfusion. These results suggest that the Na⁺-H⁺ exchanger is activated during reperfusion of the ischemic myocardium, that this activation of the exchanger contributes to ischemia-reperfusion induced cardiac dysfunction and that administration of an inhibitor of Na⁺-H⁺ exchange at reperfusion significantly attenuates the deleterious effects of exchanger activation.     

Exercise-induced splitting of the inorganic phosphate peak: investigation by time-resolved 31P-nuclear magnetic resonance spectroscopy

To investigate the splitting of the inorganic phosphate (Pi) peak during exercise and recovery, a time-resolved ³¹phosphorus nuclear magnetic resonance spectroscopy (³¹P-MRS) technique was used. Seven healthy young sedentary male subjects performed knee flexion exercise in the prone position inside a 2.1-T magnet, with the surface coil for ³¹P-MRS being placed on the biceps femoris muscle. After a 1-min warm-up without loading, the exercise intensity was increased by 0.41 W at 15-s intervals until exhaustion, followed by a 5-min recovery period. The ³¹P-MRS were recorded every 5 s during the rest-exercise-recovery sequence. Computer-aided contour analysis and pixel imaging of the Pi and phosphocreatine peaks were performed. Five of the seven subjects showed two distinct Pi peaks during exercise, suggesting two different pH distributions in exercising muscle (high pH and low pH region). In these five subjects, the high-pH increased rapidly just after the onset of exercise, while the low-pH peak increased gradually approximately 60 s after the onset of exercise. During recovery, the disappearance of the high-pH peak was more rapid than that of the low-pH peak. These findings suggest that our method ³¹P-MRS provides a simple approach for studying the kinetics of the Pi peak and intramuscular pH during exercise and recovery.     

Inhibitors of adenosine catabolism improve recovery of dog myocardium after ischemia

Summary The effects of inhibitors of adenosine catabolism on contractile function and metabolites were assessed during 15 minutes of ischemia followed by 30 minutes of reperfusion in the open-chest dog heart. As compared to sham treatment, pretreatment with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and dipyridamole (DP) protected contractile function during ischemia, and improved recovery of high energy phosphate content and contractile fucntion during reperfusion following ischemia. Testing EHNA and DP in a free-radical generating system indicated both compounds have some scavenging ability, suggesting the effect of EHNA + DP may not be on adenosine nucleotide metabolism alone. Comparison of end diastolic segment lengths to contractile function indicated the results were not affected by changes in preload resulting from peripheral vasodilation.With the technical assistance of Dennis Dahmen.     

Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion

Survival of cardiac patients undergoing heart surgery depends critically upon the recovery of myocardial energy metabolism during reperfusion of ischemic myocardium. The present study compares various parameters of myocardial energy metabolism using an isolated in situ pig heart. The left anterior descending (LAD) coronary artery was occluded for 60 min, followed by 60 min of global hypothermic cardioplegic arrest and 60 min of reperfusion. Free radical scavengers [superoxide dismutase SOD and catalase] were used to protect the ischemic heart from reperfusion injury. In both control and SOD plus catalase-treated groups, ATP, creatine phosphate (CP), ATP/ADP ratio, energy charge and phosphorylation potential dropped significantly during ischemic insult. After reperfusion, CP, ATP/ADP ratio and phosphorylation potential improved significantly, but they were restored to control level only in treated animals. In either case, free energy of ATP hydrolysis (delta G) lowered only by 5% during ischemia, but recovered promptly upon reperfusion. SOD and catalase also improved coronary blood flow and reduced creatine kinase release compared to those of untreated animals, suggesting improved myocardial recovery upon reperfusion. Our results suggest that SOD and catalase significantly improve the myocardial recovery during reperfusion by enhancing rephosphorylation steps, and the value of delta G is more critical compared to those of ATP and CP for myocardial recovery.     

Characterization of the phosphatidylinositol-specific phospholipase C-released form of rat osseous plate alkaline phosphatase and its possible significance on endochondral ossification

S-2-(3 aminopropylamino) ethylphosphorothioic acid (WR-2721) shown to surpass radical scavenging thiols in their radioprotective efficacy in cancer-type diseases has been tested for its protective potential in the reperfused heart. We investigated the radical scavenger properties of the compound in a radical generating systemin vitro as well as in isolated rat hearts subjected to 30 min ischaemia and 30 min reperfusion with the electron-paramagnetic resonance spin trap technique. The action on high-energy phosphates is observed by means of phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy while its influence on left ventricular systolic segmental length change (SSLC) during 60 min reperfusion following 60 min regional ischaemia was assessed with a fibreoptic system in anaesthetized open-chest rats. WR-2721 (0.1 mM) reduced the vascular concentration of radical adduct in isolated hearts by up to 78% (275±84% of pre-ischaemic baseline values vs 1260±413%, p<0.05) between 5 and 12.5 min reperfusion. This was accompanied by a reduction of the left ventricular end diastolic pressure to pre-ischaemic values at 30 min of reperfusion (9±6 mmHg vs 42±8 mmHg in the absence of WR-2721, p<0.02). An accelerated recovery of creatine phosphate levels (78±5% of pre-ischaemia values vs 41±5% within 60 min reperfusion; p<0.05) was observed under similar conditions with NMR-spectroscopy, although the post-ischaemic tissue content of adenosine triphosphate was not affected. The administration of WR-2721 (0.5 mmol/kg body weight) ledin situ to an accelerated restoration of contractile activity in the post-ligated left ventricular area reflected by the post-ischaemic recovery of SSLC (64±10% of pre-ischaemic values compared with 27±6% in control animals 60 min following reperfusion; p<0.02). The present data confirm an effective reduction in the exposure of the reperfused heart to endogenously released free radicals by WR-2721, a partial preservation of high-energy phosphates and an improvement in post-ischaemic contractility and encourage further investigation of such favourable action in injured myocardium.     

Expression of Na+/HCO3- cotransporter and its role in pH regulation in mouse parotid acinar cells

Ion transporters such as Na(+)/H(+) exchanger (NHE), Cl(-)/HCO(3)(-) exchanger (AE), and Na(+)/HCO(3)(-) cotransporter (NBC) are known to contribute to the intracellular pH (pH(i)) regulation during agonist-induced stimulation. This study examined the mechanisms for the pH(i) regulation in the mouse parotid and sublingual acinar cells using the fluorescent pH-sensitive probe, BCECF. The pH(i) recovery from agonist-induced acidification in the sublingual acinar cells was completely blocked by EIPA, a NHE inhibitor. However, the parotid acinar cells required DIDS, a NBC1 inhibitor, in addition to EIPA in order to block the pH(i) recovery. Moreover, RT-PCR analysis detected the expression of pancreatic NBC1 (pNBC1) only in the parotid acinar cells. These results provide strong evidence that the mechanisms for the pH(i) regulation are different in the two types of acinar cells, and pNBC1 contributes to pH(i) regulation in the parotid acinar cells, whereas NHE is likely to be the exclusive pH(i) regulator in the sublingual acinar cells.     

The effect of high buffer cardioplegia and secondary cardioplegia on cardiac preservation and postischemic functional recovery: a 31P NMR and functional study in Langendorff perfused pig hearts.

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.     

Effect of Dichloroacetate on Regional Energy Metabolites and Pyruvate Dehydrogenase Activity During Ischemia and Reperfusion in Gerbil Brain

The objective of this study was to determine whether administration of dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), improves recovery of energy metabolites following transient cerebral ischemia. Gerbils were pretreated with DCA, and cerebral ischemia was produced using bilateral carotid artery occlusion for 20 min, followed by reperfusion up to 4 h. DCA had no effect on the accumulation of lactic acid and the decrease in ATP and phosphocreatine (PCr) during the 20-min insult, nor on the recovery of these metabolites measured at 20 and 60 min reperfusion. However, at 4 h reperfusion, levels of ATP and PCr were significantly higher in DCA-treated animals than in controls, as PCr exhibited a secondary decrease in caudate nucleus of control animals. PDH was markedly inhibited at 20 min reperfusion in both groups, but was reactivated to a greater extent in DCA-treated animals at 60 min and 4 h reperfusion. These results demonstrate that DCA had no effect on the initial recovery of metabolites following transient ischemia. However, later in reperfusion, DCA enhanced the postischemic reactivation of PDH and prevented the secondary failure of energy metabolism in caudate nucleus. Thus, inhibition of PDH may limit the recovery of energy metabolism following cerebral ischemia.     

Enhanced prostaglandin production in the ischemic-reperfused myocardium by captopril linked with its free radical scavenging action

Captopril, an angiotensin converting enzyme inhibitor, has been shown to increase prostaglandin production by an as yet unknown mechanism, which this study was designed to explore. Isolated rat heart was perfused by the Langendorff technique for 15 minutes in the presence or absence of captopril. Ischemia was then induced for 60 minutes by terminating the coronary flow, followed by 60 minutes of reperfusion. Our results indicate that captopril stimulated prostaglandin and thromboxane production, but it inhibited malonaldehyde formation. Coronary flow and high energy phosphate compounds were increased, but lactate dehydrogenase and creatine kinase release decreased, demonstrating cardioprotective effects. Captopril also inhibited the production of hydroxyl radical in the heart during reperfusion, suggesting that stimulated prostaglandin production may be linked with the generation of free radicals via the eicosanoid system.