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1.
败血症休克过程中心肌肌浆网钙摄取功能的变化及其机理探讨 总被引:1,自引:0,他引:1
本工作在大鼠盲肠结扎加穿孔(CLP)腹膜炎败血症休克模型上休克不同阶段心肌肌浆网(SR)钙摄取功能的变化,并探讨了其变化机制。结果显示:败血症休克早期,心肌SR摄钙初速率降低,但SR最大摄钙量及Ca^2+-ATPase活性没有明显变化;败血症休克晚期,心肌SR摄钙初速率、最大摄钙量以及Ca^2+-ATPase活性显著降低。测定Xa^2+,Mg^2+和ATP对早、晚期要克大鼠心肌SR钙泵的亲和力以及 相似文献
2.
低氧对高原鼠兔肝细胞内质网和心肌肌浆网Ca^2+泵的影响 总被引:1,自引:0,他引:1
模拟高原低氧条件研究高原鼠兔肝细胞内质网(Endoplasmicreticulum,ER)和心肌肌浆网(Sarcoplasmicreticulum,SR)钙泵功能变化。实验设对照组(海拔2300m)和两个低氧实验组(模拟海拔5000m和7000m)。24h急性低氧时,海拔5000m组高原鼠兔ER的Ca2+泵活性无变化,海拔7000m组高原鼠兔ERCa2+泵活性下降29.02%。7d亚急性低氧时高原鼠兔SR的Ca2+泵活性无显著变化。高原鼠兔ER的Ca2+泵活性在海拔5000m组和7000m组分别升高32.50%和33.33%。25d慢性低氧时高原鼠兔ER,SR的Ca2+泵活性均无显著变化.表明:急性低氧对Ca2+泵功能有抑制作用,低氧7d后抑制缓解,至25d低氧时趋于恢复。 相似文献
3.
本研究采用离体乳头肌灌流技术,观察了模拟失重4周大鼠大鼠心肌收缩性能的变化。同时采取改变细胞外液中Ca^2+浓度,用La^3+置换细胞膜部位Ca^2+,以及快速冷却等干预实验方法,探讨模拟失重大鼠心肌收缩性能发生改变的可能机制。结果表明:模拟失重大鼠乳头肌钙反应的时间明显缩短;冷挛缩实验中的ESC/RCC60与RCC1/RCC60比值也显著降低。这些均提示模拟失重大鼠心肌收缩性能降低可能与心肌细胞 相似文献
4.
血管紧张素Ⅱ对大鼠心肌肌浆网Ca~(2+),Mg~(2+)-ATPase基因转录调节的影响 总被引:2,自引:0,他引:2
观察血管紧张素Ⅱ(AngⅡ)对心肌肌浆网Ca2+,Mg2+-ATPase基因(SERCA2a)转录调节的影响,评价DMP811对此效应的干预作用.6周龄雄性SD大鼠随机分为3组,每组6只.组1:生理盐水输注;组2:AngⅡ输注+DMP811管饲(3mg·d-1·kg-1);组3:AngⅡ输注(200ng·min-1·kg-1.1周后称其体重,取心脏并称重,提取心脏总RNA后采用Northernblot的方法检测SER-CA2a的转录水平,采用RT-PCR检测AngⅡ1型受体(AT1)mRNA水平.实验后,组3心重(CW)、心重/体重(C/B)、AT1受体转录水平均高于组1(分别增加4.7±0.4%,4.9±0.9%和24.7±3.5%;P<0.01),而SERCA2a基因转录水平显著低于组1(降低20.1±3.0%,P<0.01),并且SERCA2amRNA水平与AT1受体mRNA水平呈负相关(r=-0.74,P<0.01).AngⅡ导致的上述改变能被DMP811完全阻断.AngⅡ通过其Ⅰ型受体的介导,诱导了SERCA2a的转录下调 相似文献
5.
不同频率电刺激膈神经导致膈肌肌浆网Ca~(2 )-ATPase和Ca~(2 )释放-摄取动力学改变 总被引:1,自引:1,他引:0
研究不同频率慢性电刺激(CES)后兔膈肌肌浆网(SR)Ca2+-ATPase活性以及SR Ca2+摄取-释放动力学对不同频率CES的适应性变化。建立不同频率CES组;用定磷法测定SR Ca2+-ATPase活性;用Fura-2荧光法测定SR Ca2+摄取-释放动力学。与对照组比较,慢性低频电刺激10 Hz和20Hz组的SR Ca2+-ATPase活性明显降低(P<0.01),Ca2+释放-摄取动力学也显著降低(P<0.01);慢性高频电刺激50 Hz和100Hz组的SR Ca2+-ATPase活性则显著升高(P<0.01),Ca2+释放-摄取动力学亦明显升高(P<0.01)。实验提示,CES后不同频率CES导致膈肌SRCa2+-ATPase、Ca2+摄取-释放动力学产生不同的适应性变化;对不同功能状态的膈肌应用不同频谱的慢性电刺激可能具有重要的临床意义。 相似文献
6.
咖啡因和茶碱对大鼠皂素蜕膜心肌肌钙蛋白Ca^2+敏感性和肌浆网Ca^2+… 总被引:1,自引:0,他引:1
在低浓度皂素制备的浆膜蜕变(通透性增高)而肌浆网(SR)膜无损的蜕膜心肌标本上,以其收缩的幅度作为SR Ca^2+释放的半定量指标;高浓度皂素(500μg/ml)制备的浆膜和SR膜均蜕变的蜕膜心肌标本,以其张力-pCa关系曲线以及产生50%最大张力所需的Ca^2+浓度作为肌钙蛋白Ca^2+敏感性的定性和定量指标。结果观察到:(1)在低浓度皂素蜕膜心肌标本上,5和10mmol/L咖啡因分别引起约89 相似文献
7.
氧自由基对大鼠心肌细胞核钙转运系统的影响 总被引:6,自引:1,他引:5
观察氧自由基对心肌细胞核钙转运系统的影响。方法;大鼠心肌细胞核采用蔗糖密度梯度心分离纯化,用酶学方法测定了ATPase活性,用^45Ca^2+同位素法测定下摄取。结果;低浓度的H2O2短时间作用使核钙泵活性增加31.6%,高浓度H2O2使核钙泵活性降低,呈时间和剂量信赖性。 相似文献
8.
热应激大鼠心肌钙代谢的变化及其机理探索 总被引:1,自引:0,他引:1
心肌细胞内钙离子对心功能的调节有着极其重要的作用。本研究观察了不同热应激强度下大鼠心肌细胞内质网、线粒体中钙含量,Ca2+-ATP酶活力,内质网Ca2+主动转运速率及心肌ATP含量的变化。研究结果表明,热应激大鼠心肌细胞内质网、线粒体钙含量随肛温升高显著下降;大鼠肛温达42℃时,其钙含量分别较对照下降32.2%和46.5%;心肌细胞内质网和线粒体Ca2+-ATP酶活力亦明显降低,线粒体Ca2+-ATP酶活力下降幅度更为激烈。热应激大鼠心肌内质网Ca2+主动转运速率和Ca2+-ATP酶活力变化趋势相同,且两者呈密切相关关系。热应激大鼠心肌ATP含量亦随肛温升高大幅度降低,当动物肛温超过42℃时,其可降至对照动物的37.5%;热应激大鼠心肌ATP含量的变化与内质网Ca2+-ATP酶活力关系密切。实验结果提示:热应激心肌细胞质膜受损所致细胞Ca2+主动转运功能紊乱及心肌能量代谢障碍是心肌钙稳态失调的主要原因;心肌细胞钙代谢紊乱是诱导心肌细胞严重受损,导致热应激机体心血管功能失调,甚至心功能衰竭的重要机制 相似文献
9.
粉防己碱对大鼠心肌缺血再灌注时心肌ATP酶活性的影响 总被引:6,自引:0,他引:6
实验旨在观察在体大鼠短暂缺血后心肌膜ATP酶活性的变化及粉防己碱(Tet)的作用。分离缺血15min、再灌注2h后及在缺血再灌注前给Tet的大鼠心肌粗制质膜和内质网,测定质膜Na+-K+-ATP酶和内质网Ca2+-ATP酶活性。结果表明,心肌缺血15min后二酶活性均明显降低,分别为假结扎组的63.6%和72.6%(P<0.01),再灌注后Na+-K+-ATP酶活性有所恢复,再灌注30min时为假结扎组的72.1%(P<0.01),而Ca2+-ATP酶活性则进一步下降,再灌注30min时为假结扎组的50.4%(P<0.01),再灌注后2h二酶活性分别升高至假结扎组的80.9%和65.3%(P<0.01)。在缺血前20min分别给予Tet64.2和96.3μmol/kg及硝苯啶(0.23μmol/kg),能明显减少内质网Ca2+-ATP酶活性的降低。结果提示心肌膜ATP酶活性的降低可能参与了短暂心肌缺血所致再灌注损伤的发生机制,Tet可减少缺血和/或再灌注时内质网Ca2+-ATP酶活性降低。 相似文献
10.
将大鼠置于模拟海拔8km高度的低压舱内缺氧1周及缺氧后空气中常氧恢复1周和2周,观察了左右心室功能、心肌肥厚、心肌收缩蛋白含量及其Ca ̄(2+),Mg ̄(2+)-ATP酶活性的动态变化。结果表明,8km缺氧1周后肺动脉压及右心室收缩压明显升高,左右心室±dp/dtmax及收缩指数明显降低。左右心室肌明显肥厚,心肌收缩蛋白Ca ̄(2+),Mg ̄(2+)-ATP酶活性明显减低。缺氧后常氧恢复1和2周后,左右心室功能逐渐恢复达到或接近正常水平,心肌肥厚逐渐减轻或恢复正常,心肌收缩蛋白Ca ̄(2+),Mg ̄(2+)-ATP酶活性也逐渐升高。因此说明:心肌收缩蛋白Ca ̄(2+),Mg ̄(2+)-ATP酶活性的改变是心功能变化的重要生化基础之一,它的减低是缺氧心肌对环境的代偿适应。 相似文献
11.
Shao Q Ren B Saini HK Netticadan T Takeda N Dhalla NS 《American journal of physiology. Heart and circulatory physiology》2005,288(4):H1674-H1682
This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca(2+) transport, protein content, and gene expression. Imidapril (1 mg.kg(-1).day(-1)) was given for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited a fourfold increase in left ventricular end-diastolic pressure, whereas rates of pressure development and decay were decreased by 60 and 55%, respectively. SR Ca(2+) uptake and Ca(2+) pump ATPase, as well as Ca(2+) release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also decreased by approximately 55-65%. Imidapril treatment of infarcted animals improved cardiac performance and attenuated alterations in SR Ca(2+) pump and Ca(2+) release activities. Changes in protein content and mRNA levels for SR Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR Ca(2+) transport were not only seen at different intervals of MI but were also simulated by another angiotensin-converting enzyme inhibitor, enalapril, and an ANG II receptor antagonist, losartan. These results suggest that blockade of the renin-angiotensin system may increase the abundance of mRNA for SR proteins and, thus, may prevent the depression in SR Ca(2+) transport and improve cardiac function in congestive heart failure due to MI. 相似文献
12.
Developmental changes in cardiac sarcoplasmic reticulum in sheep 总被引:4,自引:0,他引:4
Physiologic studies suggest that the myocardium from fetal and newborn sheep functions at a higher contractile state with decreased contractile reserve when compared to the myocardium of adult sheep. To investigate the role of Ca2+ transport by the sarcoplasmic reticulum (SR) in this phenomenon, we studied functional properties and protein composition of cardiac SR vesicles isolated from fetal and maternal sheep. Active accumulation of Ca2+ and the density of the Ca2+ pump protein were decreased 60% (p less than 0.01) in fetal SR vesicles; however Ca2+-dependent ATPase activity was decreased only 30% (p less than 0.01). This decreased difference in Ca2+-dependent ATPase activities was accounted for by the higher turnover number measured for the Ca2+ pump of fetal SR vesicles (1.6-fold increased, p less than 0.01). Ryanodine, an alkaloid which blocks Ca2+ efflux from cardiac SR vesicles, stimulated Ca2+ uptake more effectively in fetal SR vesicles, suggesting that these vesicles had a higher passive Ca2+ permeability during conditions of active Ca2+ transport. Protein compositional studies showed that the content of phospholamban was decreased in fetal SR vesicles and was correlated with the decrease in the density of Ca2+ pumps. In contrast, the content of calsequestrin and the density of [3H]nitrendipine-binding sites were increased approximately 2-fold in fetal SR vesicles. These functional and compositional differences between SR vesicles isolated from fetal and maternal sheep may indicate that there is relatively more junctional SR in fetal hearts. Since the SR regulates muscle contraction by modulating intracellular Ca2+ concentration, it is possible that developmental alterations in cardiac SR may contribute to the decreased myocardial contractile reserve noted in fetal sheep. 相似文献
13.
Ren B Shao Q Ganguly PK Tappia PS Takeda N Dhalla NS 《Canadian journal of physiology and pharmacology》2004,82(12):1118-1127
Although it is generally accepted that the efficacy of imidapril, an angiotensin-converting enzyme inhibitor, in congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR) proteins has not been fully understood. In this study, we examined the effects of long-term treatment of imidapril on mortality, cardiac function, and gene expression for SL Na+/K+ ATPase and Na+ -Ca2+ exchanger as well as SR Ca2+ pump ATPase, Ca2+ release channel (ryanodine receptor), phospholamban, and calsequestrin in CHF due to myocardial infarction. Heart failure subsequent to myocardial infarction was induced by occluding the left coronary artery in rats, and treatment with imidapril (1 mg.kg(-1).day(-1)) was started orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed hemodynamically and the heart and lung were examined morphologically. Some hearts were immediately frozen at -70 degrees C for the isolation of RNA as well as SL and SR membranes. The mortality of imidapril-treated animals due to heart failure was 31% whereas that of the untreated heart failure group was 64%. Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced morphological changes in the heart and lung. The depressed SL Na+/K+ ATPase and increased SL Na+-Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing hearts were partially prevented by imidapril. Although changes in gene expression for SL Na+/K+ ATPase isoforms as well as Na+-Ca2+ exchanger and SR phospholamban were attenuated by treatments with imidapril, no alterations in mRNA levels for SR Ca2+ pump proteins and Ca2+ release channels were seen in the untreated or treated rats with heart failure. These results suggest that the beneficial effects of imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression. 相似文献
14.
Zarain-Herzberg Angel Afzal Nasir Elimban Vijayan Dhalla Naranjan S. 《Molecular and cellular biochemistry》1996,163(1):285-290
Myocardial infarction in rats induced by occluding the left coronary artery for 4, 8 and 16 weeks has been shown to result in congestive heart failure (CHF) characterized by hypertrophy of the viable ventricular myocardial tissue. We have previously demonstrated a decreased calcium transport activity in the sarcoplasmic reticulum (SR) of post-myocardial infarction failing rat hearts. In this study we have measured the steady state levels of the cardiac SR Ca2+-pump ATPase (SERCA2) mRNA using Northern blot and slot blot analyses. The relative amounts of SERCA2 mRNA were decreased with respect to GAPDH mRNA and 28 S rRNA in experimental failing hearts at 4 and 8 weeks post myocardial infarction by about 20% whereas those at 16 weeks declined by about 35% of control values. The results obtained by Western blot analysis, revealed that the immunodetectable levels of SERCA2 protein in 8 and 16 weeks postinfarcted animals were decreased by about 20% and 30%, respectively. The left ventricular SR Ca2+-pump ATPase specific activity was depressed in the SR preparations of failing hearts as early as 4 weeks post myocardial infarction and declined by about 65% at 16 weeks compared to control. These results indicate that the depressed SR Ca2+-pump ATPase activity in CHF may partly be due to decreased steady state amounts of SERCA2 mRNA and SERCA2 protein in the failing myocardium. 相似文献
15.
I E Takács J Szabó K Nosztray A J Szentmiklósi A Cseppent? J Szegi 《General physiology and biophysics》1985,4(3):271-278
Myocardial contractility and Ca2+-pump function of sarcoplasmic reticulum (SR) were studied on hearts of untreated, thyroidectomized and thyroxine-treated rats. In hypothyroid rats the contractile force, the maximum velocity of tension development and relaxation significantly decreased (by 73.2%, 68.2%; and 67.8%, respectively), while the time to peak tension was prolonged (by 25.9%) as compared with the control group. In hyperthyroidism opposite changes were found. Since the transport of calcium opposite changes were found. Since the transport of calcium by SR plays an important role in controlling contraction and, first of all, relaxation of muscle, function of the sarcoplasmic reticulum was also investigated under the above experimental conditions. In thyroidectomized rats the rate of Ca2+-uptake and Ca2+-activated ATPase activity of SR significantly decreased (by 31.7% and 61.0%, respectively), while Ca2+-binding remained unchanged. After thyroxine treatment both the Ca2+-uptake and binding capacity of SR were even decreased (by 25.6% and 12.9%, respectively), in spite of an increase in Ca2+-activated ATPase activity (by 67.3%). These changes in Ca2+ transport function of cardiac SR may only partially be responsible for the abnormalities in contraction and relaxation observed in hearts from hypo- and hyperthyroid rats. 相似文献
16.
17.
Sathish V Xu A Karmazyn M Sims SM Narayanan N 《American journal of physiology. Heart and circulatory physiology》2006,291(1):H88-H96
This study investigated Ca2+ -cycling properties of sarcoplasmic reticulum (SR) in right ventricle (RV) and left ventricle (LV) of normal rat myocardium. Intracellular Ca2+ transients and contractile function were monitored in freshly isolated myocytes from RV and LV. SR in RV displayed nearly fourfold lower rates of ATP-energized Ca2+ uptake in vitro than SR of LV. The Ca2+ concentration required for half-maximal activation of Ca2+ transport was nearly twofold higher in SR of RV. The lower Ca2+ -sequestering activity of SR in RV was accompanied by a matching decrement in Ca2+ -induced phosphoenzyme formation during the catalytic cycle of the Ca2+ -pumping ATPase (SERCA2). Western immunoblot analysis showed that protein levels of Ca2+ -ATPase and its inhibitor phospholamban (PLN) were only approximately 15% lower in SR of RV than in SR of LV. Coimmunoprecipitation experiments revealed that PLN-bound, functionally inert Ca2+ -ATPase molecules in SR of RV greatly exceed (> 50%) that in SR of LV. Endogenous Ca2+/calmodulin-dependent protein kinase-mediated phosphorylation of SR substrates did not abolish the huge disparity in SR Ca2+ pump function between RV and LV. Intracellular Ca2+ transients, evoked by electrical field stimulation, were significantly prolonged in RV myocytes compared with LV myocytes, mainly because of slow decay of intracellular Ca2+ concentration. The slow decay of intracellular Ca2+ concentration in RV and consequent decrease in the speed of RV relaxation may promote temporal synchrony of the end of diastole in RV and LV. The preponderance of functionally silent SR Ca2+ pumps in RV reflects a higher diastolic reserve required to protect and maintain RV function in the face of a sudden rise in afterload or resistance in the pulmonary circulation. 相似文献
18.
I E Takács J Szabó K Nosztray J Szegi 《Acta biologica Academiae Scientiarum Hungaricae》1981,32(1):75-81
The purpose of the present study was to compare the ATPase activities of cardiac SR in two species in which the different intrinsic myocardial contractility can only partially be explained by the different properties of cardiac myosins. In cardiac SR isolated from rat heart, the total ATPase activity was 1512.5 +/- 23.3 nmol Pi/mg protein/min, nearly four times as high as in dog cardiac SR (408.8 +/- 28.9 nmol Pi/mg protein/min). The Ca2+-activated ATPase in rat cardiac SR represented only 23.8% of the total ATPase activity, while in dog cardiac SR it was approximately 50% of the total. Thus, the specific Ca2+-activated ATPase was nearly two times higher in the cardiac SR of the rat than in that of the dog. This higher rate of ATP hydrolysis in rat cardiac SR may be, at least in part, responsible for the increased intensity and shorter duration of the active state in the rat myocardium. Polyacrylamide gel electrophoresis of SR showed that the relative amount of Ca2+-pump protein was two times higher in dog heart, similar to the percentage of Ca2+-activated ATPase activity. At the same time, the specific Ca2+-activated ATPase activity and the relative amount of Ca2+ pump protein in both the rat and dog cardiac SR were inversely related. 相似文献
19.
Preparation and characterization of longitudinal tubules of sarcoplasmic reticulum from fast skeletal muscle 总被引:1,自引:0,他引:1
Sarcoplasmic reticulum (SR) serves a central role in calcium uptake and release, thereby regulating muscle relaxation and contraction, respectively. Recently, we have isolated fractions referable to longitudinal tubules (R2) and terminal cisternae (R4), the two major types of sarcoplasmic reticulum (A. Saito et al. (1984) J. Cell Biol. 99, 875-885). The terminal cisternae contain two types of membranes, the calcium pump membrane and the junctional face membrane. The terminal cisternae are filled with electron-opaque contents which serve as a Ca2+ reservoir. The longitudinal tubules consist mainly of the calcium pump membrane. In this study, we describe a new longitudinal tubule fraction (F2) and characterize it together with the R2 and R4 SR fractions. The calcium pump membrane of the longitudinal tubules is a highly specialized membrane consisting of about 90% calcium pump protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive changes in morphology can be observed in the SR fractions referable to osmotic differences during the fixation conditions using either glutaraldehyde-tannic acid or osmium tetroxide fixatives. The changes include swelling or shrinkage and aggregation of the compartmental contents when the fixative contains calcium ions. The two types of SR have different osmotic permeability to the same medium, as indicated by differential swelling or shrinkage. Both longitudinal tubule and terminal cisternae vesicles of SR appear larger and are spherical vesicles when the glutaraldehyde-tannic acid fixative is isotonic as compared with the "standard" fixation method. We have previously reported that the ruthenium red-sensitive calcium release channels are localized to the terminal cisternae. The terminal cisternae as isolated are leaky to Ca2+ since these channels are in the "open state" (S. Fleischer et al. (1985) Proc. Natl. Acad. Sci USA 82, 7256-7259). Thus, the Ca2+, Mg2+-dependent ATPase (Ca2+ ATPase) rate is only slightly enhanced in the presence of a Ca2+ ionophore, which dissipates the Ca2+ gradient across the SR membrane. We now find that preincubation with ruthenium red restores the tight coupling of the Ca2+ ATPase activity to Ca2+ transport. That is to say, ATPase activity is reduced and the addition of ionophore stimulates the Ca2+ ATPase activity 4- to 7-fold. The Ca2+ ATPase activity in longitudinal tubules is already tightly coupled. It is minimal after a Ca2+ gradient has been generated, but can be stimulated 9- to 20-fold when the Ca2+ gradient is dissipated with ionophore. This finding suggests that the Ca2+ ATPase activity in SR is tightly coupled to Ca2+ transport in situ. 相似文献
20.
Hampton TG Wang JF DeAngelis J Amende I Philipson KD Morgan JP 《American journal of physiology. Heart and circulatory physiology》2000,279(6):H2846-H2854
Enhanced gene expression of the Na(+)/Ca(2+) exchanger in failing hearts may be a compensatory mechanism to promote influx and efflux of Ca(2+), despite impairment of the sarcoplasmic reticulum (SR). To explore this, we monitored intracellular calcium (Ca(i)(2+)) and cardiac function in mouse hearts engineered to overexpress the Na(+)/Ca(2+) exchanger and subjected to ischemia and hypoxia, conditions known to impair SR Ca(i)(2+) transport and contractility. Although baseline Ca(i)(2+) and function were similar between transgenic and wild-type hearts, significant differences were observed during ischemia and hypoxia. During early ischemia, Ca(i)(2+) was preserved in transgenic hearts but significantly altered in wild-type hearts. Transgenic hearts maintained 40% of pressure-generating capacity during early ischemia, whereas wild-type hearts maintained only 25% (P < 0.01). During hypoxia, neither peak nor diastolic Ca(i)(2+) decreased in transgenic hearts. In contrast, both peak and diastolic Ca(i)(2+) decreased significantly in wild-type hearts. The decline of Ca(i)(2+) was abbreviated in hypoxic transgenic hearts but prolonged in wild-type hearts. Peak systolic pressure decreased by nearly 10% in hypoxic transgenic hearts and >25% in wild-type hearts (P < 0.001). These data demonstrate that enhanced gene expression of the Na(+)/Ca(2+) exchanger preserves Ca(i)(2+) homeostasis during ischemia and hypoxia, thereby preserving cardiac function in the acutely failing heart. 相似文献