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     

去白细胞血液预防家兔缺血心肌再灌注损伤的实验研究

用涤纶纤维滤器去除再灌注血液中的白细胞，旨在检验其对缺血心肌再灌注损伤的保护效应。３２只家兔随机分成对照组和实验组，分别用全血和去白细胞血再灌注－离体心脏在２８℃下缺血６０ｍｉｎ后再灌注２０ｍｉｎ。结果表明：对照组白细胞计数、ＣＶＲ、ＣＰＫ及ＣＰＫ－ＭＢ显著高于实验组（Ｐ〈０．００１～Ｐ〈０．０５）；ＳＯＤ活性下降，ＭＤＡ含量明显增高与实验组相比有显著差异，分别为Ｐ〈０．０２及Ｐ〈０．０５。线粒体     

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。     

迷走神经预调对心肌缺血再灌注损伤预防作用的实验研究

目的：探讨心脏迷走神经预调对心脏缺血再灌注损伤的预防作用及其机制,以建立一种新的围手术期心肌保护方法。方法：实验用健康杂种犬１６只,随机均分为对照且（Ｃ组）和迷走神经预调组（Ｐ组）。常规建立体外循环,分别于主动脉阻断前以３０Ｈｚ,０．５ｍｓ,１０Ｖ方波刺激心脏迷走神经３ｍｉｎ,间隔３ｍｉｎ,重复２次。转流前、主动脉阻断前、复跳即刻,再灌注３０ｍｉｎ,６０ｍｉｎ时测心输出量（ＣＯ）,射血分数（ＥＦ）     

微血管顿抑与血管内皮细胞保护

心肌顿抑及微血管顿抑是心脏缺血再灌注后可逆性损伤的两种表现。微血管顿抑可影响顿抑心肌的功能恢复，并在某种程度上加重顿抑心肌的组织学损害，促使其向不可逆方面发展。氧自由基造成内皮细胞系统损害是微血管顿抑的核心内容。加强血管内皮细胞保护，促进心功能的恢复，是心脏外科手术心肌保护中不可忽视的方面。     

微血管顿抑与血管内皮细胞保护

心肌顿抑及微血管顿抑是心脏缺血再灌注后可逆性损伤的两种表现。微血管顿抑可影响顿抑心肌的功能恢复,并在某种程度上加重顿抑心肌的组织学损害,促使其向不可逆方面发展。氧自由基造成内皮细胞系统损害是微血管顿抑的核心内容。加强血管内皮细胞保护,促进心功能的恢复,是心脏外科手术心肌保护中不可忽视的方面。     

单次灌注高钾晶体心脏停搏液对未成熟心肌能量代谢和功能的影响

目的为了探讨未成熟心肌保护的方法,研究低温、多次和单次灌注高钾晶体心脏停搏液对未成熟心肌能量代谢和功能的影响。方法将２４只新西兰幼兔随机分成４组,对照组,低温组（Ⅰ组）,多次灌注组（Ⅱ组）：多次高钾晶体心脏停搏液灌注和单次灌注组（Ⅲ组）：单次高钾晶体心脏停搏液灌注。建立离体工作心模型,利用高效液相色谱法（ＨＰＬＣ）和分光光度法检测未成熟心肌缺血前、后心肌高能磷酸化合物、三磷酸腺苷（ＡＴＰ）、磷酸肌酸（ＣＰ）和糖原含量,并检测缺血前、后的心功能。结果缺血再灌注后,Ⅱ组ＡＴＰ,ＣＰ和糖原保存最差,分别为４．０±０．４μｍｏｌ／ｇ干重,５．８±０．４μｍｏｌ／ｇ干重和６３９±４０μｇ／ｇ干重,Ⅰ组和Ⅲ组则相应分别为６．１±０．３μｍｏｌ／ｇ干重,８．８±０．５μｍｏｌ／ｇ干重,７３２±３７μｇ／ｇ干重（Ｐ＜０．０１）和６．０±０．４μｍｏｌ／ｇ干重,９．０±０．５μｍｏｌ／ｇ干重,７７６±５０μｇ／ｇ干重（Ｐ＜０．０１）;心功能方面,Ⅲ组均优于Ⅰ组和Ⅱ组（Ｐ＜０．０１）。结论单次灌注高钾晶体心脏停搏液对未成熟心肌能量代谢和功能的保护效果最佳     

抑肽酶对成年豚鼠心肌再灌注损伤的保护作用

目的：探索抑肽酶的心肌保护作用。方法：建立离体心脏顺行灌注后左心做功模型，２０只成年豚鼠随机分为Ａ、Ｂ两组，分别以４℃Ｓｔ．ＴｈｏｍａｓＨｏｓｐｉｔａｌｃａｒｄｉｏｐｌｅｇｉｃｓｏｌｕｔｉｏｎＮｏ．２（ＳＴＳ）和ＳＴＳ＋抑肽酶（１５０ＫＩｕｍＬＳＴＳ）为心停搏液，测定缺血（９０分钟，２０℃）前、后和再灌注（６０分钟）时心脏动力学指标，心肌腺苷酸和丙二醛含量，并行心肌电镜观察。结果：Ｂ组再灌注后的心功能恢复，腺苷酸贮备和超微结构的改善明显高于或优于Ａ组，而丙二醛含量显著低于Ａ组（Ｐ＜０．０５）。结论：抑肽酶加入ＳＴＳ中可减少氧自由基产生，对成年豚鼠心肌缺血再灌注损伤有保护作用。     

St.ThomasⅡ液对心肌微循环及内皮细胞的作用

目的 观察Ｓｔ．ＴｈｏｍａｓⅡ液对心肌微循环及内皮细胞（ＥＣ）的作用。方法 制作离体心灌注模型，分缺血停跳组（Ａ）；单次灌注停跳液组（Ｂ）；多次灌注停跳液组（Ｃ）。测定生理指标及毛细血管密度和充盈率；观察心肌及内皮细胞超微结构的改变。结果复跳后三组ｄｐ／ｄｔ均有下降，Ａ组尤明显（Ｐ〈０．０１）；五羟色胺只增加Ｂ、Ｃ组冠状血管流量（Ｐ〈０．０１）；硝酸甘油增加冠状血管流量，Ｂ、Ｃ组多于Ａ组（Ｐ〈０     

Effects of postischemic left ventricular pressure-volume unloading on contractile recovery and myocardial blood flow in the regionally stunned canine heart.

OBJECTIVE: Myocardial stunning remains a clinical problem without definitive therapy. This study tested the hypothesis that mechanical therapy with a ventricular assist device would accelerate recovery of contractility in stunned myocardium by increasing the postischemic myocardial blood flow. METHODS: Regional stunning was induced in dogs (25 kg) by 15 minutes of coronary occlusion and 180 minutes of reperfusion. One group (ventricular assist device; n = 10) was reperfused in conjunction with left ventricular unloading with a centrifugal-pump ventricular assist device. A second group (control; n = 8) underwent unmodified reperfusion. Hemodynamic and regional function data were acquired in all dogs with the heart in the working state before and during ischemia and after 180 minutes of reperfusion. Regional myocardial blood flow was measured at these same intervals and after 30 minutes of reperfusion, at which time the left ventricle was mechanically unloaded in animals with a ventricular assist device. RESULTS: Regional stunning was observed in all animals, but cardiogenic shock developed in none of them. After 180 minutes of reperfusion, animals with a ventricular assist device had greater systolic shortening in the risk segment than did control animals (11.5% +/- 2.8% vs 1.1% +/- 1.3%; P <.05) and had no differences in either the slope or x-axis intercept of regional preload recruitable stroke work relations compared with preischemic values. Differences in contractile recovery did not correlate, however, with postischemic myocardial blood flow. Hyperperfusion mediated by the ventricular assist device was not observed in either stunned or remote segments. CONCLUSIONS: Mechanical left ventricular unloading attenuates regional myocardial stunning within 3 hours in normotensive dogs, independent of effects on myocardial blood flow. The mechanism underlying this effect remains undefined, but these data support expanded use of mechanical therapy for stunned myocardium in clinical settings.     

环孢菌素A逆转利多卡因对七氟醚后处理心肌保护的作用

Objective To study the effects of lidocaine on sevoflurane postconditioning-induced cardioprotection.Methods Ischemic status was kept for 40 rain in isolated perfused rat hearts followed by 1 h of reperfusion.Sevoflurane(3%) was administered at the beginning of reperfusion for 15 rain with or without lidocaine (20 μg/ml) perfusion.The direct mitochondrial permeability transition pore (MPTP) inhibitor Cyclosporin A (CsA,0.2 μmol/L) was co-administered in the presence or absence of lidocaine.LVDP,LVEDP,+dp/dtmax were recorded and infarct size was measured with TTC staining.Results Sevoflurane postconditioning significantly improved the recovery of ischernic myocardial function and decreased the infarct size of rat hearts (P＜0.05),which was abolished by lidocaine perfusion.The inhibition of lidocaine on sevoflurane posteonditioning effect was reversed by CsA.Conclusion Sevoflurane postconditioning effectively protects myocardium against ischemia/reperfusion injury,and higher concentration of lidocaine inhibits this protective effect by opening MPTP.     

Gadolinium attenuates regional stunning in the canine heart in vivo

OBJECTIVE: Gadolinium, a lanthanide cation, ameliorates pathophysiologic features of both heart failure and cardiac arrhythmias. We have shown, in an in vitro model, that gadolinium blocks stretch-induced contractile dysfunction in both normal and stunned myocardium. The present study tested the hypothesis that gadolinium would also attenuate regional myocardial stunning in an in vivo model. METHODS: Mongrel dogs (n = 13) were subjected to regional myocardial ischemia (occlusion of the left anterior descending coronary artery) for 15 minutes, followed by reperfusion for 180 minutes. Intravenous gadolinium (500 micromol) was given to 7 dogs before ischemia; no gadolinium was given to control animals. Regional contractile function was assessed serially by means of both systolic shortening (percentage) and regional preload recruitable stroke work. RESULTS: Administration of gadolinium before ischemia had no effect on heart rate, arterial blood pressure, stroke volume, or regional contractile function. Ischemia resulted in paradoxical systolic bulging in both groups. After 180 minutes of reperfusion, systolic shortening was enhanced in gadolinium-treated animals compared with that in control animals (10.9% +/- 1.5% vs 2.4% +/- 1.7%, P =.003). Both the slope and x-axis intercept of regional preload recruitable stroke work returned to preischemic values in treated animals but remained abnormal in control animals. CONCLUSIONS: These data confirm that gadolinium attenuates regional myocardial stunning in vivo. Gadolinium may cause peripheral vasodilatation but does not appear to exert positive inotropic effects on the normal canine heart. The mechanism underlying gadolinium-mediated effects on stunned myocardium remains undefined, but this study suggests that use of gadolinium may represent a novel adjunct to current cardioprotective strategies.     

Enhanced interstitial fluid adenosine attenuates myocardial stunning.

Reversible myocardial dysfunction associated with transient ischemia has been termed the stunned myocardium. Because exogenous adenosine has been shown to protect the ischemic myocardium, we hypothesized that augmentation of endogenous adenosine levels would attenuate myocardial stunning. To induce stunning, anesthetized dogs were subjected to 15 minutes of ischemia (left anterior descending artery occlusion) followed by 60 minutes of reperfusion. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 5 mg/kg/hr), an adenosine deaminase inhibitor, was used to augment adenosine levels. The effect of EHNA on interstitial fluid (ISF) adenosine levels, coronary blood flow, and regional systolic wall thickening was compared with that of an untreated group (n = 8). EHNA increased preischemia ISF adenosine levels threefold and was associated with a corresponding increase in coronary blood flow. EHNA administration did not alter preischemia systolic wall thickening. Although ISF adenosine increased fourfold during ischemia in the untreated group, ISF adenosine increased nearly sixtyfold above preischemia values in the EHNA-treated group and remained elevated throughout reperfusion. Postischemic regional function was enhanced significantly in the group treated with EHNA. These data show that adenosine deaminase inhibition increased ISF adenosine levels and attenuated myocardial stunning. Metabolic manipulation of myocardial ISF nucleoside levels may be beneficial in limiting postischemic myocardial dysfunction.     

Amino acid substrate preloading and postischemic myocardial recovery.

During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.     

Effects of gadolinium on regionally stunned myocardium: temporal considerations

OBJECTIVES: The lanthanide cation, gadolinium (Gd(3+)), accelerates recovery of stunned myocardium when given prior to ischemia. This study sought to determine whether giving Gd(3+) during ischemia or during reperfusion also ameliorates stunning, as these temporal relationships could help determine the clinical utility of this novel agent. METHODS: Regional myocardial stunning was induced in anesthetized dogs by coronary occlusion for 15 min followed by reperfusion for 3 h. Gd(3+) (500 micromol) was given intravenously in three treatment groups: [1] preischemia; [2] during ischemia; [3] after reperfusion. No Gd(3+) was given to controls (Group 4). Measures of global and regional myocardial function were assessed serially. RESULTS: Treatment with Gd(3+) prior to ischemia (Group 1) had no effects on hemodynamics or regional contraction. Coronary occlusion resulted in diastolic lengthening and paradoxical systolic bulging equally in all groups. After 3 h of reperfusion, regional systolic shortening (%) in the stunned segment was greater in Groups 1 (10.9 +/- 3.4; P = 0.02) and 2 (6.6 +/- 1.3; P = 0.047) compared with controls (-0.6 +/- 0.03). Recovery of systolic function (% of baseline shortening) after 3 h of reperfusion was similarly improved in Groups 1 (56.1 +/- 16.8; P = 0.02) and 2 (43.3 +/- 8.1; P = 0.04) compared with controls (-11.5 +/- 4.7). CONCLUSIONS: Gadolinium has no inherent inotropic effects but enhances recovery of stunned myocardium. This effect appears maximal if Gd(3+) is given prior to ischemia, indicating potential utility in elective cardiac surgical procedures or percutaneous coronary interventions. Gadolinium also enhances recovery if given during ischemia but prior to reperfusion, and may thus be useful in acute coronary syndromes as well.     

Possible involvement of Na(+)-H+ exchange in the early phase of reperfusion in myocardial stunning.

Calcium overload during reperfusion after prolonged ischemia has been associated with the Na(+)-Ca2+ exchange system. It has been proposed that the promotion of Na(+)-Ca2+ exchange at reperfusion may be mediated by Na(+)-H+ exchange. To evaluate whether this hypothesis is applicable for stunned myocardium, we examined the influence of temporary suppression of Na(+)-H+ and/or Na(+)-Ca2+ exchange during early reperfusion in isolated rat hearts. Myocardial stunning was produced by global ischemia for 15 min at 37 degrees C. The initial reperfusate was given during the subsequent 10 min after ischemia, and followed by reperfusion with normal Krebs-Henseleit buffer solution for 40 min. Hemodynamic indices, creatine kinase in coronary effluent, and myocardial water content were measured during reperfusion. The functional recovery of stunned myocardium was improved with higher extracellular Na+ concentration and/or lower Ca2+ concentration of the initial reperfusate. Aortic flow recovery of group II (135 mM Na(+)-0.5 mM Ca2+) was 77.0 +/- 3.4%, which was substantially greater (P < 0.05) than that of other groups: group I (control, 135 mM Na(+)-1.5 mM Ca2+), 68.2 +/- 2.4%; group III (25 mM Na(+)-0.5 mM Ca2+), 48.7 +/- 2.9%; group IV (25 mM Na(+)-1.5 mM Ca2+), 21.6 +/- 1.5%. Administration of amiloride, an inhibitor of Na(+)-H+ exchange, in the initial reperfusate ameliorates cardiac damage and improved aortic flow recovery in a dose-dependent manner (10(-6) M, 70.1 +/- 3.7%; 10(-5) M, 77.3 +/- 1.7%; 10(-4) M, 82.0 +/- 2.1% vs control 68.2 +/- 2.4%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Triiodothyronine on Stunned Myocardium

Abstract Administration of thyroid hormone, triiodothyronine (T₃), causes numerous cardiovascular effects such as increases in stroke volume, cardiac output, heart rate, and myocardial contractility, and decreases in systemic vascular resistance. Along with other stressors, cardiopulmonary bypass (CPB) has been associated with reduced levels of T₃. We examined the effects of T₃ on early postischemic myocardial recovery in rabbit hearts subjected to crystalloid perfusion to simulate a low T₃ state, and in pig hearts following global ischemia due to CPB. Studies using the former system showed that T₃ administration results in significantly improved developed pressure after reperfusion of mildly ischemic hearts compared to controls, without producing inotropic effects. In more severely stunned rabbit hearts, physiologic and 10 times physiologic doses of T₃ produced significantly improved (p < 0.05) stroke work end-diastolic length compared to placebo treatment. T₃ treated pigs undergoing CPB and subjected to 30 minutes of global normothermic ischemia experienced significantly enhanced recovery of left ventricular contractility compared to controls at 90 and 120 minutes post reperfusion. Neither placebo nor T₃ affected myocardial adenosine triphosphate levels. These data show that T₃ enhances recovery from myocardial stunning without producing acute inotropic effects.     

Ischemic preconditioning in the aged heart —Myocardial protective effect as compared with the mature heart—

It is now well established that pre-treatment with sublethal ischemia, followed by reperfusion, will delay myocardial necrosis during a later sustained ischemic episode, termed ischemic preconditioning (IPC); this has been confirmed experimentally and clinically. However, the effects for the senescent heart differ from those of the mature heart at both functional and cellular levels which have not yet been determined. Comparisons were made between aged (>135 weeks, n=18) and mature (15～20 weeks, n=8) rabbit hearts which underwent 30 min. normothermic global ischemia with 120 min reperfusion in a buffer-perfused isolated, paced heart model, and the effects of IPC on post-ischemic functional recovery and infarct size were investigated. Ischemic preconditioned hearts (n=6) were subjected to one cycle of 5 min. global ischemia and 5 min. reperfusion prior to global ischemia. Global ischemic hearts (n = 6) were subjected to 30 min. global ischemia without intervention. Control hearts (n = 6) were subjected to perfusion without ischemia. Post-ischemic functional recovery was better in the ischemic preconditioned hearts than in the global ischemic hearts in both aged and mature hearts. However, in the aged hearts, post-ischemic functional recovery was slightly reduced compared to that of the mature hearts, and only the coronary flow was well-preserved. In the mature hearts, myocardial infarction in the ischemic preconditioned hearts (14.9 ± 1.3%) and in the control hearts (1.0 ± 0.3%) was significantly decreased (p<0.01) compared to that of the global ischemic hearts (32.9 ± 5.1%). In the aged hearts, myocardial infarction in the ischemic preconditioned hearts (18.9 ± 2.7%) and in the control hearts (1.1 ± 0.6%) was significantly decreased (p<0.001) compared to that of the global ischemic hearts (37.6 ± 3.7%). The relationship between infarct size and post-ischemic functional recovery of left ventricularpeak developed pressure (LVDP) was linear and the correlation negative, with r=?0.934 (p<0.001) and ?0.875 (p<0.001) for mature and aged hearts respectively. The data suggest that, in the senescent myocardium, the cellular pathways involved ischemic preconditioning responses that were post-ischemic, and that functional recovery was worse as compared to that of the mature myocardium. Furthermore, the effects of post-ischemic functional recovery became consistently weaker during the control period of 120 min. reperfusion after a prolonged ischemic insult in a buffer perfused isolated rabbit model. However, the effects of infarct size limitation were well-preserved in both senescent and mature myocardia.     

Adenosine and the Stunned Heart

Abstract Adenosine is one agent under investigation as a therapeutic intervention of myocardial stunning. Adenosine caused numerous effects on the cardiovascular system through its interaction with A₁ and A₂ receptors. We investigated adenosine A₁ receptor mediated mechanisms of cardiac protection in the stunned rat myocardium. Previous studies showed that both adenosine and R-phenylisopropyladenosine (PIA), an A₁ receptor agonist, prolonged the time to onset of ischemic contracture in ischemic isolated rat hearts. Phenylaminoadenosine, an A₂ receptor agonist, did not have any effect, while receptor antagonists blocked adenosine and PIA action. Direct attenuation of the effects of myocardial stunning was observed by altering levels of interstitial fluid adenosine. Our laboratory has shown that administration of erthro-9(2-hydroxy-3-nonyl) adenine (EHNA; an adenosine deaminase inhibitor) to dogs subjected to left anterior descending coronary artery (LAD) occlusion followed by reperfusion results in dramatic increases in ischemic levels of interstitial fluid adenosine and postischemic myocardial function. Using a similar model in dogs, we have shown that exogenous intracoronary adenosine (50 μg/kg per min) augmented postischemic recovery of function, as assessed by significant enhancement (p < 0.01) of systolic wall thickness (7.0 ± 3.0 pretreatment vs ?5.7 ± 1.7 controls). These data support the role for an adenosine A₁ receptor mediated mechanism for protection against myocardial stunning.