成年、新生豚鼠心脏缺血再灌注期间功能、代谢和形态改变

目的研究比较成年和新生豚鼠心脏缺血再灌注期间的功能、代谢、形态的不同改变，为心肌保护提供依据。方法建立离体心脏左心做功模型，以ＳｔＴｈｏｍａｓＨｏｓｐｉｔａｌｃａｒｄｉｏｐｌｅｇｉｃｓｏｌｕｔｉｏｎⅡ（ＳｔＴｈｏｍａｓⅡ号液）为心停搏液，测定成年豚鼠（Ａ组）和新生豚鼠（Ｂ组）心脏缺血前、后和再灌注时（或后）动力学，心肌腺苷酸和丙二醛的含量，并行电子显微镜观察。结果Ｂ组再灌注时（或后）的心功能恢复，心肌腺苷酸贮备和超微结构的改善均低于Ａ组（Ｐ＜０．０５），而丙二醛的含量高于Ａ组（Ｐ＜０．０５）。结论以ＳｔＴｈｏｍａｓⅡ号液为心停搏液时，新生豚鼠心肌在缺血再灌注期间受损程度重于成年豚鼠，氧自由基的产生在其中起重要作用。     

卡托普利抗心肌缺血再灌注损伤的实验研究

用兔体外循环心肌再灌注损伤模型，研究卡托普利（ｃａｐｔｏｐｒｉｌ，Ｃａｐ）的心肌保护作用。２０只兔随机均分为２组，建立体外循环后在主动脉阻断同时灌注４℃心脏停跳液，对照组为Ｓｔ．ＴｈｏｍａｓＩ号液，实验组在Ｓｔ．ＴｈｏｍａｓＩ号液中加入Ｃａｐ（０．５ｍｇ／ｋｇ）。心脏缺血９０分钟和再灌注６０分钟后结果显示，实验组心肌Ｃａ＋＋、丙二醛（ＭＤＡ）、心肌酶（ＬＤＨ，ＣＰＫ）较对照组显著降低，心肌超微结构损伤明显减轻。结论：Ｃａｐ对缺血再灌注心肌起到了良好的保护效果。     

钾通道开放剂对离体兔心肌缺血/再灌注损伤的保护作用

目的　观察三磷酸腺苷敏感性钾通道开放剂（ＫＣＯｓ）Ｐｉｎａｃｉｄｉｌ（１０μｍｏｌ／Ｌ）对兔心肌缺血／再灌注损伤的保护作用。方法　采用离体兔心Ｌａｎｇｅｎａｏｒｆｆ灌注实验模型,离体兔心１６只随机等分成对照组和Ｐｉｎｎａｃｉｄｉｌ组。离体兔心肌缺血４０分钟后再灌注２０分钟,Ｐｉｎａｃｉｄｉｌ组于心脏停跳前增加Ｐｉｎａｃｉｄｉｌ（１０μｍｏｌ／Ｌ）灌注１５分钟,对比观察再灌注后５、１０、１５、２０分钟心功能的恢复率以及再灌注２０分钟心肌形态学结构、腺苷酸含量、脂质过氧化物丙二醛的变化。结果　再灌注后Ｐａｉｎａｃｉｄｉｌ组心率的恢复率、心肌收缩力的恢复率明显高于对照组,心肌ＭＤＡ的含量明显低于对照组（Ｐ＜０．０５或０．０１）,ＡＴＰ、ＴＡＮ、ＥＣ含量明显高于对照组,形态学观察Ｐｉｎａｃｉｄｉｌ组结构损伤较轻。结论Ｐｉｎａｃｉｄｉｌ（１０μｍｏｌ／Ｌ）预处理明显增强离体兔心肌缺血／再灌注期心功能的保护效果,降低 ＡＴＰ的消耗,减少脂质过氧化物的形成。     

冷血心肌麻痹液温度与保护效果关系的研究

目的：评价冷血心肌麻痹液（ＣＢＣ）心肌保护的温度效应关系。方法：离体工作鼠心模型,观察ＣＢＣ ４℃,８℃,１２℃,１６℃和２０℃停搏１２０分钟再灌注４５分钟对心功能,超微结构、心肌肌浆网（ＳＲ）Ｃａ＾２＋－ＡＴＰａｓｅ活性和Ｃａ＾２＋摄取恢复的改变。结果：４℃￣１２℃组心功能,超微结构及ＳＲ Ｃａ＾２＋－ＡＴＰａｓｅ活性和Ｃａ＾２＋摄取恢复均优于１６℃和２０℃组。结论：温度为影响ＣＢＣ心肌保护效果     

抑肽酶心肌保护机制的探讨

目的 探讨抑肽酶增强Ｓｔ．ＴｈｏｍａｓⅡ停跳液心肌保护作用的机制。方法 用离体豚鼠工作心脏模型，研究４℃、３３℃下不同剂量抑肽酶增强Ｓｔ．ＴｈｏｍａｓⅡ型跳液心肌保护效果，记录停跳前后心脏血流动力学和心肌酶学。结果 在４℃下抑肽酶能增加复灌后心肌ＡＴＰ的保存量，并存在剂量依赖关系；同时性马抑肽酶能明显减少保存后心肌酶的释放、并改善保存后心肌的超微结构；但抑肽酶组停跳后的心功能，较对照组无明显提高；     

卡托普利心脏停搏液对缺血再灌注心肌NOS活性和NO产生的影响

目的：探讨卡托普利心脏停搏液对缺血再灌注心肌保护作用的机制。方法：１２只绵羊,随机均分为对照组（Ｉ组）和卡托普利组（Ｉ组）。常规建立体外循环,心脏停搏６０分钟,再灌注３０分钟。Ｉ组采用仁济医院冷晶体停搏液,ＩＩ组在停搏液中加入卡托普利２３μｍｏｌ／Ｌ。观察冠状窦血中一氧化氮（ＮＯ）、肌酸磷酸激酶（ＣＰＫ）、环磷酸鸟苷（ｃＧＭＰ）、心肌丙二醛（ＭＤＡ）含量及心肌ＮＯ合酶（ＮＯＳ）同功酶活性的变化,监测心肌功能。结果：再灌注后Ｉ组心肌血ＮＯ、ＣＰＫ、ｃＧＭＰ、心肌ＭＤＡ均明显升高,Ｉ组低于Ｉ组（Ｐ＜０．０５或０．０１）。ＩＩ组再灌注后心肌原生型ＮＯ合酶（ｃＮＯＳ）活性明显高于Ｉ组,而诱导型ＮＯ合酶（ｉＮＯＳ）及总ＮＯＳ活性显著低于Ｉ组（Ｐ＜０．０１或０．００１）。两组再灌注后心肌功能均降低,Ｉ组较Ｉ组更为显著。再灌注后ＮＯ的变化与心肌ＭＤＡ和ＣＰＫ之间呈正相关（Ｐ＜０．００１和０．０１）。结论：缺血再灌注心肌损伤与过量ＮＯ产生有关,卡托普利通过调节ＮＯＳ同功酶活性,维持正常ＮＯ水平起到保护作用。     

改良的St.Thomas停跳液对未成年兔心肌的保护作用

目的 探讨不同停跳液对未成年兔心肌缺血再灌注损伤的保护作用。方法 应用离体心脏工作模型对１６只未成年兔心脏灌注改良的Ｓｔ．ＴｈｏｍａｓＮｏ１停跳液（Ａ组）及改良的Ｓｔ．ＴｈｏｍａｓＮｏ２停跳液（Ｂ组）,观察经１５℃缺血１２０ｍｉｎ再灌注６０ｍｉｈ后兔心功能恢复情况。结果 离体心脏再灌注后,１５℃血２ｈ条件下,Ｂ组心功能恢复明显好于Ａ组,而心肌含水率,冠脉漏出液的肌酸磷酸激酶及乳酸脱氢酶及心肌细胞超     

卡托普利对心肌组织高能磷酸化合物代谢的影响

观察含卡托普利（巯甲丙脯酸）的停搏液及再灌注血液对心肌组织高能磷酸化合物代谢的影响。用杂种犬１６条，随机分为对照组（Ｓｔ．Ｔｈｏｍａｓ改型停搏液）、卡托普利（ｃｐｌ）组（含ｃｐｌ４．６μｍｏｌ／Ｌ的Ｓｔ．Ｔｈｏｍａｓ停搏液改型及再灌注血液）。测定心肌组织三磷酸腺苷（ＡＴＰ）、二磷酸腺苷（ＡＤＰ）、一磷酸腺苷（ＡＭＰ）、肌酸肌苷（ＣＰ）、丙二醛（ＭＤＡ）含量、股动脉及冠状静脉窦血气及乳酸值，计算心肌氧摄取率。结果表明，心脏复跳后ｃｐｌ组ＡＴＰ、ＡＤＰ、ＡＭＰ及ＣＰ的恢复率、心肌氧摄取率均明显高于对照组，而心肌组织ＭＤＡ含量、冠状静脉窦与股动脉的血乳酸含量差值明显低于对照组。提示含４．６μｍｏｌ／Ｌｃｐｌ的停搏液及再灌注血液可改善心肌组织氧的供需平衡，增加心肌组织氧摄取率及乳酸利用率，增加ＡＴＰ的合成，从而改善心肌缺血再灌注后心肌组织的能量代谢及心功能     

体外循环中人参二醇组皂甙的心肌保护作用

为观察人参二醇组皂甙（ＰＤＳ）对体外循环（ＣＰＢ）手术病人的心肌保护作用，将６０例ＣＰＢ手术病人，随机均分为对照组与ＰＤＳ组。ＰＤＳ组术前２天和术前３０分钟，按１５ｍｇ／ｋｇ，共３次，静脉滴注ＰＤＳ。测定两组ＣＰＢ期间（转流前、转流１５、３０分钟、再灌注１５、３０、６０分钟）血清超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）含量。结果发现ＣＰＢ时间与ＳＯＤ活性成反比，与ＭＤＡ含量成正比。两组ＳＯＤ活性总均数ＰＤＳ组较对照组高，差异显著（Ｐ＜０．０１）；两组ＭＤＡ含量总均数ＰＤＳ组较对照组低，差异有显著性（Ｐ＜０．０１）。结论：术前应用ＰＤＳ可显著提高ＣＢＰ手术病人ＳＯＤ活性，减少ＭＤＡ生成，从而防治心肌再灌注损伤。     

甲状腺激素T3增补于心脏停搏液中对心肌的保护作用

目的　探讨Ｔ３ 增补于停搏液中的心肌保护作用。方法　离体鼠心（ ｎ ＝ １６） 在改良的ＬａｎｇｅｎｄｏｒｆｆＮｅｅｌｙ 灌注模型上、３７ ℃下经历２０ 分钟预灌注、２０ 分钟停搏、３０ 分钟再灌注。结果　再灌注３０ 分钟时,左室功能指标（ＬＶＤＰｄｐ／ｄｔ）百分恢复率治疗组显著高于对照组（ Ｐ ＜０ ．０１）,心肌超氧化物歧化酶（ＳＯＤ） 治疗组显著高于对照组（ Ｐ＜ ０．０１）,过氧化脂质（ＬＰＯ） 治疗组显著低于对照组（ Ｐ ＜０．０５）;心肌酶（ＨＢＤＨ．ＬＤＨ）释放量再灌注期对应时点组间比较,治疗组显著低于对照组（ Ｐ＜ ０ ．０１） ;电镜观察心肌超微结构,治疗组显著优于对照组。结论　Ｔ３ 增补于心脏停搏液中可以显著地促进缺血后左室功能的恢复,显著减轻心肌缺血再灌注损伤,具有良好的心肌保护作用。     

大剂量抑肽酶对心肌缺血再灌注损伤的保护作用

目的　探索大剂量抑肽酶对缺血再灌注离体鼠心的影响。方法　32只雄性SD大鼠随机均分为抑肽酶组(A),对照组(B)。制成离体鼠心工作模型,分别用含有抑肽酶（1×106KIU/L）和不含抑制肽酶的克氏液灌注30min,缺血停搏40min,复灌30min。缺血前及再灌注期间测定血液动力学指标、肌磷酸激酶含量、心脏干湿重比,对心肌超微结构作定性观察。结果　再灌注后,A组心功能、冠脉流量的恢复、超微结构的改善明显优于B组,肌磷酸激酶含量明显低于B组（P＜0.05）。结论　大剂量抑肽酶对缺血再灌注心肌有保护作用。     

肝素对顿抑心肌功能影响的实验研究

目的：探讨肝素化剂量肝素对在体家兔短暂缺血－再灌注顿抑心肌的功能的影响。方法：23只雄性家兔，分为实验（A）组和对照（B）组，建立在体心肌短暂缺血（15min）－再灌主（60min）损伤模型。A组于前降支阻断前20min给予肝素（700U／kg）。分别于给药前、缺血前、再灌注期间，检测2组NO、ET－1、MDA、SOD水平，测定血流动力学指标变化，对心肌超微结构做定性观察。结果：A组在给药后20min，NO含量即较给药前明显升高（P＜0．05），且在整个再灌注期较B组有显著性差别（P＜0．05），心功能、超微结构明显改善。结论：肝素参与短暂缺血－再灌注顿抑心肌功能的保护，机制可能是通过药物性预适应，增强内皮源性NO的产生，从而减轻心肌缺血－再灌注损伤。     

Response of hypertrophied myocardium to ischemia: correlation with biochemical and physiological parameters

The increased susceptibility of hypertrophied hearts to ischemic injury during cardiac operations has long been recognized. Although the imbalances in oxygen supply and demand which may occur with hypertrophy during hypotension, ventricular fibrillation, or reperfusion have been extensively studied, the biochemical response of hypertrophied myocardium to ischemia has not been fully elucidated. In the present investigation, rat hearts in which hypertrophy was induced by chronic pressure overload were used to examine the relationship of the physiological parameter, ischemic contracture, to high-energy phosphate content and mitochondrial function during global ischemia. Hypertrophied hearts developed ischemic contracture after significantly shorter duration of ischemia than did normal hearts (5.8 +/- 0.3 minutes versus 10.1 +/- 0.7 minutes). High-energy phosphate content was lower in hypertrophied hearts at control and at ischemic contracture initiation and completion than in normal hearts, whereas mitochondrial function was consistently greater in the hypertrophy group. This investigation demonstrates that the hypertrophied myocardium, independent of flow-related events, is more vulnerable to ischemic injury than normal myocardium and suggests that the increased susceptibility may result from lower high-energy phosphate stores present at the onset of ischemia. The results emphasize the need for rapid cardiac arrest with the induction of ischemia in hypertrophied myocardium and suggest the potential for increasing myocardial high-energy phosphate content in the hypertrophied ventricle by interventions such as arrested perfusion with substrate containing oxygenated cardioplegic solutions prior to the onset of planned ischemia.     

Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart

OBJECTIVE: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. METHODS: The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by means of measurement of creatine kinase and myeloperoxidase activity within the myocardium, as well as histochemical analysis. RESULTS: Aprotinin (20,000 U/kg) administrated 2 minutes before reperfusion significantly attenuated myocardial injury expressed as creatine kinase washout compared with that seen in vehicle-treated rats (65 +/- 25 vs 585 +/- 98 creatine kinase difference in units per 100 mg, P <.01). Administration of 5000 U/kg of the protease inhibitor resulted in partial inhibition of myocardial reperfusion injury. Moreover, cardiac myeloperoxidase activity in the ischemic myocardium, a marker of neutrophil accumulation, was significantly reduced after aprotinin treatment. Histologic analysis of the reperfused myocardium demonstrated reduced polymorphonuclear leukocyte infiltration and reduced tissue injury. Furthermore, aprotinin treatment resulted in decreased induction of cardiac myocyte apoptosis compared with that seen in vehicle-treated rats. CONCLUSIONS: Inhibition of serine proteases with aprotinin appears to be an effective means of preserving ischemic myocardium from reperfusion injury, even after 24 hours of reperfusion. Aprotinin might exert cardioprotection through inhibition of polymorphonuclear leukocyte-induced myocardial injury and inhibition of reperfusion-induced apoptosis of cardiac myocytes.     

阿片受体在缺血预处理中的作用

目的　研究阿片受体激动在缺血预处理限制心肌梗死(心梗)范围作用中的地位。方法　建立在体家兔心脏缺血再灌注模型,观察阿片受体拮抗剂纳洛酮对缺血预处理心肌保护作用的影响。在离体兔心模型上,观察阿片受体激动剂吗啡代替短暂缺血刺激,对随后发生的急性心梗范围的影响,并用纳洛酮及蛋白激酶C阻断剂Chelerythrine分别进行干预。电镜观察吗啡预处理对离体心脏缺血心肌超微结构改变的影响。结果　在体心脏模型上,5min缺血及10min再灌注的预处理可显著缩小随后30min缺血引起的心梗范围(P＜0.01);在预处理前10min或30min、缺血前5min给予纳洛酮均可使预处理所产生的限制心梗范围的作用消失。离体心脏经历5min全心缺血及10min再灌注的预处理后,可缩小心梗范围(P＜0.05);在缺血前如给予吗啡预灌注15min,亦可缩小心梗范围(P＜0.05),其作用可被纳络酮或Chelerythrine分别阻断。30min缺血后心肌线粒体等超微结构严重受损,如给吗啡预灌流,心肌损伤明显减轻。结论　阿片受体激动参与了缺血预处理的心肌保护;吗啡预处理可以减轻缺血心肌损伤及产生限制心梗范围的心肌保护作用;吗啡是通过心脏局部的阿片受体介导,激活蛋白激酶C从而产生心肌保护作用。     

腺苷后处理对大鼠心肌缺血再灌注时血清IL-10和TNF-α浓度的影响

目的 探讨腺苷后处理对大鼠心肌缺血再灌注时血清IL-10和TNF-α浓度的影响.方法 雄性SD大鼠24只,体重180～250 g,随机分为4组(n=6):假手术组(S组)、缺血再灌注组(IR组)、缺血后处理组(IP组)和腺苷后处理组(AP组).IR组、IP组和AP组结扎冠状动脉左前降支30 min后恢复再灌注.IP组缺血30 min时进行再灌注30 s缺血30 s,循环3次,然后再灌注120 min;AP组缺血30 min时静脉输注腺苷40 μg·kg-1·min-1,剂量1.5 mg/kg,然后再灌注120 min.于缺血前(基础状态)、缺血30 min、再灌注30、120 min时记录HR、SP和DP.再灌注120 min时采集动脉血样,测定血清IL-10和TNF-α的浓度.采集血样后,取心肌组织,测定MDA含量及心肌梗死面积,光镜下观察心肌病理学结果.结果 与S组比较,IR组HR、SP和DP降低,IP组和AP组SP降低,IR组、IP组和AP组血清IL-10、TNF-α浓度和心肌MDA含量升高,心肌梗死面积增加(P<0.05);与IR组比较,IP组和AP组HR、SP和DP升高,血清TNF-α浓度和心肌MDA含量降低,心肌梗死面积减小,血清IL-10浓度升高(P<0.05);IP组和AP组上述指标差异无统计学意义(P>0.05).IP组和AP组心肌病理学损伤程度轻于IR组.结论 腺苷后处理可促进IL-10生成,抑制TNF-α生成,从而减轻大鼠心肌缺血再灌注损伤.     

Protective effect of lisinopril against ischemia-reperfusion injury in isolated guinea pig hearts

BACKGROUND: In order to determine whether angiotensin-converting enzyme inhibitors (ACEI s) attenuate ischemia-reperfusion injury, we investigated and compared the effects of lisinopril via different routes of administration in an isolated guinea pig heart model of ischaemia reperfusion. METHODS: The effect of lisinopril cardioplegia, oral pretreatment with lisinopril and lisinopril enriched reperfusion solution on myocardium after a normothermic global ischemia of 90 minutes and 30 minutes of reperfusion in the modified Langendorff model was randomly studied in 4 groups (n=8 in each). In all groups, cardioplegic arrest was achieved by administering St. Thomas Hospital Cardioplegic Solution (STHCS). The first group was utilized as the control. In the second group, hearts were arrested with lisinopril (1 micromol/L) enriched STHCS. In the third group, animals were pretreated with oral lisinopril (0.2 mg/kg/twice a day) for ten days. In the last group hearts were again pretreated with oral lisinopril (like in Group 3) and the heart were reperfused with lisinopril enriched (1 micromol/L) Krebs-Henseleit solution during the reperfusion period. RESULTS: Contractility, which was expressed as contractile force (g contractility/g heart weight), was preserved better in the study groups. In the last group, the hearts had the best left ventricular contractile function, where contractile force was 58.4%+/-4.82% of the preischaemic values. In Group I, Group II and Group III they achieved 29.5%+/-5.6%, 41.9%+/-4.9%, and 55.3%+/-5.8% of their preischaemic contractile force values respectively. Creatine kinase leakage was significantly lower and also post- ischaemic coronary flows were significantly higher in the 4th group. Coronary flow after reperfusion increased from 48.0+/-6.2 to 68.0+/-4.51 ml/min.g.heart, in Group IV (p<0.05). CONCLUSIONS: Myocardial MDA and GSH contents showed that there was a correlation between the depletion of myocardial GSH content and increased lipid peroxidation. The myocardial GSH content indicates that the best results were obtained in the last group as compared to the other groups. These preliminary results showed that oral preconditioning improved postischaemic myocardial function and decreased myocardial injury. Because the best results were achieved in the last group, it can be suggested that lisinopril may also play a protective role against reperfusion injury.     

Influence of pre-existing ischemia on recovery from chemical cardioplegia. A study on pig hearts in an isolated blood-perfused model.

The impact of prior cardiac ischemia on recovery from chemical cardioplegia was investigated in pig hearts. Group I hearts were subjected to 9-min normothermic ischemia before the start of chemical cardioplegia. After 180 min of induced cardiac arrest, all hearts were reperfused and monitored for 120 min in a blood-perfused Langendorff model. Consistent with left ventricular performance, myocardial oxygen uptake was significantly lower in group I than in the other hearts during the first 60 min of reperfusion. Lactate elimination was significantly higher in group I at the start of reperfusion, but showed no intergroup difference after 25 min. Nor was intergroup difference found in left ventricular end-diastolic pressure, total myocardial flow or glucose extraction fraction during reperfusion. The mitochondrial ultrastructure was identical in the two groups before chemical cardioplegia. During cardioplegia it deteriorated in group I but normalized in group II. During reperfusion these circumstances were reversed. Although precardioplegic ischemia thus significantly impaired left ventricular performance during early recovery, with corresponding effects on metabolism and ultrastructure, stable performance during reperfusion indicated that the ischemic injury did not worsen.     

抗ICAM-1单抗对体外循环下犬心肌的保护作用

目的 探讨抗ICAN-1单抗对体外循环下心肌的保护作用及可能机制.方法 应用犬体外循环心肌再灌注损伤模型,比较含抗ICAM-1单抗的灌注液干预前后心功能以及心肌组织或血浆中SOD、NDA、CPK、ATP、LA等的变化.结果 体外循环再灌注后,心功能减退,心肌组织中NDA、LA增加,SOD及ATP减少,而血浆CPK增加,发生再灌注损伤.抗ICAN-1单抗干预后心功能显著改善,心肌或血浆中原本升高的MDA、CPK、LA下降,而下降的SOD及ATP增加.结论 抗ICAN-1单抗可减少体外循环再灌注时的白细胞黏附,降低心肌自由基水平,减轻心肌损伤,产生心肌保护作用.     

Functional and metabolic protection of the neonatal myocardium from ischemia. Insufficient protection by cardioplegia

The effects of ischemia and cardiac arrest by cardioplegia on the mechanical function and energy metabolism of the ventricular myocardium of the neonatal guinea pig were investigated in the isolated perfused heart preparation and compared with these effects in the adult guinea pig. Whereas reperfusion after ischemia resulted in better recovery of mechanical function and a higher adenosine triphosphase content in the neonatal myocardium than in the adult, recovery from cardiac arrest induced by St. Thomas' Hospital cardioplegic solution was not as good in the neonatal myocardium as in the adult. Contracture developed in the neonatal myocardium on administration of the cardioplegic solution, but did not in the adult. This was considered to be the reason that the protective effect of the cardioplegic solution was inferior in the neonatal myocardium to that in the adult.