苯那普利对自发性高血压大鼠心肌缺血-再灌注心功能、氧自由基和肌浆网Ca2+-ATP酶的影响

目的:探讨血管紧张素转换酶抑制剂(ACEI)对自发性高血压大鼠(SHR)心肌缺血-再灌注心功能、氧自由基和肌浆网Ca²⁺-ATP酶的影响。方法:30只10周龄雌性SHR分为2组,SHR对照组(SHR)、SHR+B组(每日10mg/kg苯那普利);另15只同周龄、同性别Wistar大鼠作为对照组(Wistar)。治疗12周后,每组大鼠结扎左冠状动脉前降支30min,再灌注30min,观察血流动力学参数,左室心肌丙二醛(MDA)含量、超氧化物岐化酶(SOD)活性及肌浆网(SR)Ca²⁺-ATP酶活性。结果:与Wistar组比较,SHR组血压、左心室重/体重较高,左心功能损害程度较重,心肌MDA含量较高,SOD活性和SRCa²⁺-ATP酶活性较低;SHR+B组血压、左心室重/体重、左心功能损害程度,SRCa²⁺-ATP酶活性无显著性差异,但心肌MDA含量较低,SOD活性较高。结论:苯那普利可逆转SHR左室肥厚,促进缺血-再灌注心肌SRCa²⁺-ATP酶活性的恢复和减少氧自由基损害,从而减轻缺血-再灌注心功能损伤。     

挥发性麻醉药对大鼠离体心脏缺血再灌注损伤的影响

目的： 研究挥发性麻醉药对大鼠离体心脏缺血再灌注损伤的影响。方法： SD大鼠136只，随机分为17组，每组8只。采用Langendorff离体大鼠心脏模型。按给药方式分为6大组：假手术组（含1亚组）：自然灌流85 min;对照组（含4亚组）：平衡15 min为1亚组，平衡后续灌15 min为1亚组，平衡续灌后缺血10 min为1亚组，平衡续灌缺血25 min后复灌30 min为1亚组;氟烷组（含3亚组）：平衡15 min后，灌注含1.5 MAC氟烷灌注液15 min为1亚组，平衡续灌含药液后缺血10 min为1亚组，平衡续灌缺血25 min复灌含1.5 MAC氟烷的灌注液30 min为1亚组;1.5 MAC的恩氟烷、异氟烷、七氟烷大组，各大组包括3亚组，处理同氟烷组。记录各组心脏在平衡15 min、给药后(或续灌15 min)、复灌30min的左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室发展压(LVDP)、左室压力升高或降低最大速率(±dp/dtmax)、心率（HR）、冠脉流量（CF）。实验结束后测定心肌超氧化物歧化酶（SOD）活性、心肌丙二醛（MDA）含量、高能磷酸盐（ATP）含量、Na＋-K＋-ATP酶、Ca2＋-ATP酶活性。结果： （1）恩氟烷、异氟烷、七氟烷组在给药后CF高于对照组（P<0.05）；各用药组在给药后LVDP、±dp/dtmax低于对照组（P<0.01）、而LVEDP高于对照组（P<0.05）；复灌30 min各用药组LVDP、±dp/dtmax高于对照组（P<0.01）。氟烷、异氟烷组在给药后和复灌30 min的HR低于对照组（P<0.05或P<0.01）。（2）各用药组在缺血前、缺血期和复灌30 min的心肌ATP含量高于及复灌30 min SOD活性高于对照组，MDA含量低于对照组（P<0.05或P<0.01）。（3）氟烷、恩氟烷、异氟烷组在缺血前Ca2＋-ATP酶活性低于对照组、各用药组在缺血期和复灌30 min此酶活性高于对照组（P<0.05或P<0.01）。（4）在复灌30min，氟烷组的Na＋-K＋-ATP酶活性高于对照组和其它3用药组（P<0.05或P<0.01）。结论： 挥发性麻醉药可抑制心肌收缩功能，对缺血再灌注心肌有保护作用。缺血再灌注后，能明显促进心肌功能与代谢的恢复，而且能提高CF、心肌Ca2＋-ATP酶及Na＋-K＋-ATP酶活性。     

非创伤性预处理在离体心脏抗再灌注损伤中作用机制的探讨

目的:观察非创伤性肢体缺血预处理对大鼠离体再灌注心肌是否有保护作用。方法:实验采用体重(250±30)gSD雄性大鼠25只随机分成3组,在Langendorff装置上对大鼠离体心脏进行灌流。对照组(C,n=8):在灌注全程均用富氧K-H液(充以95%O₂+5%CO₂),在恒压(8.33kPa)、恒温(37℃)条件下灌注;缺氧/复氧组(A,n=8):预灌15min后,灌注心脏先全心缺血缺氧15min,随后15min复氧再灌注(37℃);非创伤性肢体缺血预处理组(N-WIP,n=9):先将大鼠双后肢捆绑5min,松开5min,反复4次后,随后的方法同R组。在相应时点分别测定冠脉流出液和心肌匀浆中超氧化物歧化酶(SOD)活性,Ca²⁺-Mg²⁺-ATP酶活性和丙二醛(MDA)含量,同时记录心肌细胞的单相动作电位(MAP)和心肌收缩张力曲线。结果:非创伤性肢体缺血预处理能使再灌注心律失常发生率显著低于A组;心肌组织中MDA含量显著低于A组,心肌组织中SOD活性显著高于A组,心肌细胞的膜电位、Ca²⁺-Mg²⁺-ATP酶活性及肌张力较稳定。结论:非创伤性肢体缺血预处理对大鼠离体再灌注心肌有明显的保护作用,可能是通过增强心肌的抗氧化能力、稳定心肌Ca²⁺-Mg²⁺-ATP酶活性和膜相结构等途径,提高心肌细胞对再灌注损伤的抵抗力。     

PTSD样情感行为异常大鼠海马ATP酶活性与Ca2+/CaM改变

目的:探讨创伤后应激障碍(PTSD)精神与行为异常的病理生理基础。方法:通过频率25Hz、波宽1ms、串长10s、串隔7min、强度100μA的恒流、单向方波, 建立海马惊厥阈下电刺激PTSD动物模型;采用神经生化、流式细胞仪、荧光标记术及Westernblotting等方法, 定量观测了实验动物海马Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶活性, 细胞内Ca²⁺含量与钙调素(CaM)相对活性平均通道荧光及海马组织总CaM表达的动态变化规律。结果:电刺激停止后48h内实验动物海马细胞线粒体Na⁺-K⁺-ATP酶活性明显下降, 72h内Ca²⁺-ATP酶活性显著降低;海马细胞[Ca²⁺]i于电刺激停止后72h内明显增高, 游离CaM平均通道荧光则同步降低, 而海马组织总CaM表达则于电刺激停止后48h内明显增多。结论:海马细胞[Ca²⁺]i持续增高、结合CaM含量明显增加及线粒体钠钾泵与钙泵功能受损, 可能是实验动物长时程PTSD样情感行为异常的重要病理生理基础之一。     

老龄大鼠脑缺血再灌注ATP酶和自由基代谢变化及其意义

目的:从ATP酶活性变化和自由基损伤方面研究老龄大鼠脑缺血再灌注损伤的机制。方法:青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组,观察大鼠全脑缺血30min再灌注60min后ATP酶和SOD活性及MDA、Ca^2＋、Na^＋、K^＋含量。结果:老龄模型组Ca^2＋水平高于青年模型组和老龄对照组。老龄对照组脑组织Na^＋-K^＋-ATP酶低于青年对照组,老龄模型组低于青年模型组。老龄对照组Ca^2＋-ATP酶低于青年对照组,老龄模型组低于青年模型组但高于老龄对照组。老龄对照组血清和脑组织中SOD活性低于青年对照组,老龄模型组低于青年模型组。老龄模型组血清和脑组织MDA/SOD比值高于老龄对照组。结论:脑缺血再灌注损伤与钙超载和自由基损伤有关,但由于老龄大鼠脑组织ATP酶和钙含量及自由基代谢的增龄变化,使脑缺血再灌注后这些病理改变较青年大鼠更为明显并具有一定特点。     

SHR心肌细胞离子泵活性与血压及左心室肥厚的相关性研究

目的:研究心肌细胞膜离子泵活性与血压及左心室肥厚之间的关系。方法:将12只自发性高血压大鼠(SHR)分成两组,一组灌喂缬沙坦(24mg/kg),另一组和6只正常大鼠(WKY)灌喂生理盐水共4周。测量实验前后血压及实验后心肌细胞膜的Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶和Mg²⁺-ATP酶活性,同时测量心肌细胞横径(TDM)和心脏重量/体重(HW/BW)。结果:SHR生理盐水组的血压和TDM及HW/BW显著高于WKY和SHR用药组(P＜0.01),Na⁺-K⁺-ATP酶和Ca²⁺-ATP酶活性显著低于WKY和SHR用药组(P＜0.01)。Ca²⁺-ATP酶活性与血压、HW/BW和TDM呈显著负相关(r=-0.5945,-0.7077和-0.5026,P＜0.01和P＜0.05);与Na⁺-K⁺-ATP酶呈显著正相关(r=0.7543,P＜0.01)。Na⁺-K⁺-ATP酶与血压呈显著负相关(r=-0.6338,P＜0.01)。结论:SHR心肌细胞膜Na⁺-K⁺-ATP酶和Ca²⁺-ATP酶活性的改变与血压和左心室肥厚之间有密切的内在关系,心肌细胞膜离子泵活性的缺陷不仅在高血压同时可在左心室肥厚的形成和发展过程中起重要作用。     

参麦注射液对大鼠急性心肌缺血再灌注损伤的影响

目的:观察参麦注射液对大鼠急性心肌缺血再灌注损伤的影响,并探讨其作用机制。方法:结扎冠状动脉左前降支10min再灌15min复制大鼠急性心肌缺血再灌注损伤模型,描记标准肢体Ⅱ导联心电图,测定心肌组织匀浆中超氧化物歧化酶(SOD)、Na⁺,K⁺-ATP酶和Ca²⁺-ATP酶活性及丙二醛(MDA)含量,电镜观察心肌线粒体改变。结果:参麦注射液使再灌注性心律失常的发生率低于模型组、持续时间较短,心肌组织匀浆中SOD、Na⁺,K⁺-ATP酶和Ca²⁺-ATP酶的活性高于模型组,MDA的含量低于模型组,心肌线粒体损伤轻于模型组。结论:参麦注射液对大鼠急性心肌缺血再灌注损伤有明显的防治作用,其机制与减轻氧自由基及钙超载损伤有关。     

ATP抑制不死化人成纤维细胞增殖信号转导机制的研究

目的:探讨ATP抑制不死化人成纤维细胞增殖信号转导机制。方法:观察0.4mmol/LATP与不死化人成纤维细胞共培养不同时间下,细胞内游离Ca²⁺浓度([Ca²⁺]i)和三磷酸肌醇(IP₃)浓度的变化特点和意义,以及分别应用Ca²⁺和K⁺通道拮抗剂时,细胞增殖率的改变。结果:ATP与不死化人成纤维细胞共培养时,[Ca²⁺]i明显升高,IP₃浓度明显降低(均P＜0.01)。分别应用Ca²⁺和K⁺通道拮抗剂时,细胞增殖率都显著增高(均P＜0.01)。结论:ATP抑制不死化人成纤维细胞增殖过程中有钙通道和钾通道以及IP₃的参与。     

金属硫蛋白在培养乳鼠心肌细胞缺氧预处理中的作用

目的:探讨金属硫蛋白(MT)在培养乳鼠心肌细胞缺氧预处理中的作用机制。方法:建立培养的乳鼠心肌细胞缺氧/复氧模型,检测心肌细胞预缺氧24 h后MT及丙二醛(MDA)含量,Na⁺-K⁺ATP酶、Ca²⁺-Mg²⁺ATP酶活性的变化以及用MT抗体阻断后的相应变化。结果:缺氧预处理组MT含量及Na⁺-K⁺ATP酶、Ca²⁺-Mg²⁺ATP酶活性显著高于对照组及缺氧/复氧组(P＜0.05),MDA含量显著低于缺氧/复氧组(P＜0.01);使用MT抗体后,酶活性则显著降低,而MDA含量显著高于未加抗体和对照组(P＜0.01)。结论:缺氧预处理产生大量MT,后者可能通过减少MDA及促进Na⁺-K⁺ATP酶、Ca²⁺-Mg²⁺ATP酶的活性升高起到保护心肌的作用。     

甲状腺功能减退对新生仔鼠心肌肌浆网钙转运蛋白表达的影响

目的: 探讨甲状腺功能减退(甲减)对新生仔鼠心肌肌浆网钙转运蛋白肌浆网Ca²⁺-ATP酶(SERCA2a)、磷酸受纳蛋白(PLB) mRNA表达以及肌浆网Ca²⁺-ATP酶活性的影响,并观察左旋甲状腺素(L-T₄)替代治疗后以上指标的改变。方法: SD孕鼠自孕15 d起每天予丙基硫氧嘧啶(PTU)(50mg/d)灌胃至仔鼠出生并持续整个哺乳期,制成围生期甲减模型,并对部分甲减仔鼠自出生当天起每天腹腔注射L-T₄(20 μg /kg)。收集甲减、治疗及对照组出生3、5、7日龄的仔鼠心室肌组织(每组10只),应用实时荧光定量PCR方法检测SERCA2a及PLB mRNA含量,并同时采用荧光分光光度计法测定心肌细胞内游离钙(MyoCa²⁺)浓度,无机磷酸根法检测心肌肌浆网钙泵活性。结果: 实时荧光定量PCR结果显示甲减组新生仔鼠心肌SERCA2a mRNA水平下降(P<0.05),PLB mRNA水平升高(P<0.01),SERCA2a/PLB下降(P<0.01);L-T₄治疗组仔鼠SERCA2a mRNA水平较甲减组上升(P<0.05),PLB mRNA水平下降(P<0.05),SERCA2a/PLB上升(P<0.01)。心肌细胞内游离钙浓度检测结果显示甲减组心肌细胞MyoCa²⁺浓度较同日龄对照组升高(P<0.01);L-T₄治疗组仔鼠心肌细胞MyoCa²⁺浓度低于同日龄甲减组仔鼠(P<0.05)。酶活性检测结果显示甲减组仔鼠肌浆网Ca²⁺-ATP酶活性低于同日龄对照组(P<0.01);L-T₄治疗组仔鼠肌浆网Ca²⁺-ATP酶活性较同日龄甲减组仔鼠升高(P<0.05)。结论: 甲状腺激素缺乏可使新生大鼠肌浆网Ca²⁺-ATP酶活性降低,并下调SERCA2a表达,上调PLB表达;肌浆网钙转运蛋白SERCA2a与PLB参与调控围生期甲减诱发的新生仔鼠心功能下降。     

氟烷和七氟醚对缺血再灌注心肌功能和氧自由基的影响

目的：研究１５肺泡最小浓度（ＭＡＣ）的氟烷和七氟醚对缺血再灌注心肌功能和氧自由基的影响。方法：应用离体大鼠心脏Ｌａｎｇｅｎｄｏｒｆ逆行灌注模型研究１５ＭＡＣ的氟烷、七氟醚对心肌缺血前后心功能的影响,测定缺血前、缺血１０ｍｉｎ、复灌３０ｍｉｎ３个不同时间的心肌超氧化物歧化酶（ＳＯＤ）活性和丙二醛（ＭＤＡ）含量。结果：七氟醚不同程度地抑制心肌收缩功能。缺血１０ｍｉｎ时,七氟醚组ＳＯＤ酶活性明显下降,ＭＤＡ含量显著升高。缺血２５ｍｉｎ复灌３０ｍｉｎ后,二药均能促进心肌功能和ＳＯＤ酶活性恢复,抑制ＭＤＡ生成,其中七氟醚的作用较为明显。结论：二药对缺血再灌注心肌具有一定的保护作用,七氟醚优于氟烷。     

二氮嗪后处理对离体大鼠心功能及线粒体心磷脂的影响

目的:建立离体大鼠心肌缺血/再灌注损伤模型,观察二氮嗪(diazoxide,D)后处理对缺血/再灌注损伤离体大鼠心功能及线粒体心磷脂的影响,并探讨ATP敏感性钾通道在二氮嗪后处理心肌保护中的作用。方法:采用Langendorff装置建立离体大鼠心肌缺血/再灌注损伤模型,将SD大鼠随机分为对照组(control)、缺血再灌注模型组(I/R)、二氮嗪后处理组(I/R+D)、5-羟葵酸拮抗二氮嗪后处理组(I/R+5-HD+D),每组8只,均先灌注平衡20 min。Control组:灌注平衡后续灌70 min;I/R组:缺血前灌注4℃ST.Thomas停跳液,全心缺血40 min,再灌30 min;I/R+D组:全心缺血40 min,缺血后给予含二氮嗪(50μmol/L)的K-H液灌注5 min后,再灌25 min;I/R+5-HD+D组:二氮嗪后处理前给予含5-羟葵酸(100μmol/L)的K-H液灌注5 min,再灌20 min。观察各组续(再)灌注末心率、冠脉流出液量、心功能、心肌酶学及心肌线粒体心磷脂的变化。结果:各组续(再)灌注末比较,I/R组较control组及I/R+D组心率减慢、冠脉流出液量降低,心功能明显受损,心肌酶增加,心磷酯含量减少,但与I/R+5-HD+D无明显差异。结论:二氮嗪后处理通过增加线粒体心磷脂含量,减少心肌酶的释放,改善心脏功能,减轻心肌的再灌注损伤,产生心肌保护作用。5-羟葵酸能够完全阻断二氮嗪的心肌保护作用。     

牛磺酸对缺血大鼠心肌线粒体Ca2+-Mg2+-ATP酶活性与MDA含量影响

目的和方法：用Ｗｉｓｔａｒ大鼠皮下注射异丙肾上腺素（ＩＳＰ,５ｍｇ／ｋｇ）诱导心肌缺血模型。观测心肌线粒体（Ｍｉｔ）中丙二醛（ＭＤＡ）含量、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性及牛磺酸（Ｔａｕ）的影响。结果：缺血组大鼠心肌Ｍｉｔ中ＭＤＡ升高８７８３％、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性分别降低３７５６％和５０２０％（Ｐ＜０．０１）。Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶活性与ＭＤＡ含量也呈显著负相关（ｒ＝－０．８７,Ｐ＜０．０１）。Ｃａ２＋－ＡＴＰ酶活性与ＭＤＡ含量也呈显著负相关（ｒ＝－０７９,Ｐ＜０．０１）。在注射异丙肾上腺素（ＩＳＰ）前３０ｍｉｎ腹腔注射Ｔａｕ（２００ｍｇ／ｋｇ）则Ｍｉｔ中ＭＤＡ含量、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶活性均未见显著异常改变。结论：Ｔａｕ可能通过抑制ＭＤＡ的生成实现其保护Ｃａ２＋－ＡＴＰ酶和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶活性的作用。     

Sodium-calcium exchange and sarcolemmal enzymes in ischemic rabbit hearts

We have investigated alterations in sarcolemmal function that occur during myocardial ischemia. Rabbit ventricles were incubated at 37 degrees C for time periods ranging from 5 min to 2 h. The ischemic tissue was homogenized, and activities of the sarcolemmal enzymes Na+-K+-ATPase, K+-p-nitrophenylphosphatase (K+-pNPPase), and adenylate cyclase were measured in the crude homogenate. Na+-K+-ATPase and K+-pNPPase were substantially inhibited after only 10 min of ischemia, and activities for all three enzymes declined progressively up to 1 h of ischemia, when activities were 37-59% of control. Highly purified sarcolemmal membranes prepared from control tissue and myocardium that had been made ischemic for 1 h showed similar purification of sarcolemmal enzymes, passive Ca2+ binding, and passive permeability to Ca2+. However, the velocity of Na+-Ca2+ exchange in ischemic sarcolemmal vesicles was reduced approximately 50% due to a reduction in Vmax. Although the parallel decline in activities of several sarcolemmal functions might suggest a change in membrane structure, phospholipid and cholesterol contents in ischemic sarcolemma were the same as control.     

Changes in catecholamine, angiotensin converting enzyme and adenosine triphosphatase in ischemic preconditioning rat hearts

Changes in catecholamine ,angiotensin converting enzy me and adenosine triphosphatase in ischemic preconditioning rat hearts     

Alterations of membrane potential and Ca2+ flux of sarcoplasmic reticulum vesicles in ischemic myocardium

The sequence of contraction-relaxation for myocardial cells is believed to be linked to Ca2+ flux across the sarcoplasmic reticulum. Alterations of sarcoplasmic reticulum function during ischemia may result in depressing the myocardial contraction-relaxation sequence. This study examines the relationship between the membrane potential and Ca2+ flux across sarcoplasmic reticulum vesicles isolated from non-ischemic and ischemic myocardium. Ischemic myocardium was produced by ligating the coronary artery of swine hearts for 15 and 30 minutes. Membrane potential was determined by use of the fluorescence-sensitive dye, 3,3'-diethylthiadicarbocyanine, and Ca2+ uptake was studied spectrophotometrically with the use of murexide. Results are as follows: (1) membrane potential and Ca2+ uptake by sarcoplasmic reticulum from ischemic myocardium progressively decreased with the length of ischemia; and (2) preincubation of sarcoplasmic reticulum from non-ischemic myocardium with deoxycholate (0.01 approximately 0.09 percent) resulted in progressively decreasing membrane potential and Ca2+ uptake. Apparently a correlation exists between membrane potential and the rate of Ca2+ uptake. These results suggest that membrane characteristics of sarcoplasmic reticulum are altered within as early as 15 minutes of the onset of ischemia. Alteration of membrane permeability in sarcoplasmic reticulum from ischemic myocardium may be responsible for the observed decrease in membrane potential and Ca2+ uptake.     

Excitation-contraction coupling in hypothermic ischemic myocardium

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.     

Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.