左心室局部心肌缺血时采用压力控制间歇闭塞冠状穴的仿真研究

为了研究左心室局部心肌缺血时采用压力控制间歇闭塞冠状穴（ＰｒｅｓｓｕｒｅＣｏｎｔｒｏｌｅｄＩｎｔｅｒ－ｍｉｔｅｎｔＣｏｒｏｎａｒｙＳｉｎｕｓＯｃｃｌｕｓｉｏｎ，简称ＰＩＣＳＯ）对心血管系统一些重要血液动力学参量的影响以及对缺血心肌的挽救作用，我们建立了一个详细的冠脉循环模型和左心室局部心肌缺血时的组分式模型，并将它们纳入我们原有的心血管循环系统模型中。在计算机仿真实验中，我们考察了缺血心肌的弹性对ＰＩＣＳＯ辅助效果的影响以及ＰＩＣＳＯ的最佳闭塞／释放时间。仿真结果指出：缺血心肌损伤越严重，弹性越小，冠状穴闭塞（ＣＳＯ）期间缺血区域的毛细血管与静脉之间的前、后向血流就越小，ＰＩＣＳＯ的辅助效果也越小；ＣＳＯ不改变心肌的耗氧量，但ＣＳＯ期间的逆向血流能给心肌增加部分供氧量；ＰＩＣＳＯ的最佳闭塞／释放时间是一组使冠状动脉血流以及毛细血管与静脉之间的前、后向血都相对最大时的折中值。     

兔心肌缺血性损伤的超微结构变化及凋亡检测

目的　探讨实验性急性心肌梗塞时不同损伤区域心肌超微结构的变化及心肌细胞是否凋亡。方法　结扎左冠状动脉的左室支建立心肌缺血模型 ,采用透射电镜、原位末端探针标记 ,对不同损伤区心肌细胞的损伤情况进行研究。结果　电镜观察显示中心缺血区心肌组织呈现缺血坏死征象 ,而梗塞交界区呈现明显的心肌细胞凋亡征象。TUNEL检测结果显示中心缺血区未见心肌凋亡细胞发生 ,而梗塞交界区有心肌凋亡细胞检出。结论　急性心梗时 ,中心缺血区和梗塞交界区损伤存在不同的发生机制     

缺血区心肌血流时相分布及其灌注压依赖性的建模与仿真研究

为了研究缺血心肌在侧支循环不同形成阶段的血流分布模式，建立了一个左心室壁血流灌注计算机仿真模型。模型中左心室壁正常心肌和缺血心肌中血管网都分为三层，每层血管网用一时变阻容网络来代表。以六条雄性犬的左心室压和主动脉压的实测数据作为输入进行仿真结果表明，用全外反搏的方法提高冠脉灌注压对缺血心肌的血流灌注有明显改善。     

辛伐他汀对慢性心力衰竭大鼠左室重构的影响

目的:探讨辛伐他汀对慢性心力衰竭大鼠心肌纤维化及心肌超微结构的影响.方法:利用腹主动脉缩窄法建立雄性Wistar大鼠心衰模型,随机分为心衰假手术组、模型组和辛伐他汀组.观察各组大鼠左心室肌质量指数(LVMI),H-E和Massion染色观察左心室心肌形态结构变化,电镜下观察左心室心肌的超微结构,SP免疫组织化学检测左心室心肌中结缔组织生长因子(CTGF)表达情况,RT-PCR测定各组大鼠左心室心肌CTGF mRNA水平.结果:与假手术组相比,模型组LVIM、心肌胶原容积分数(CVF)、CTGF蛋白及mRNA表达明显上升.与模型组相比,辛伐他汀组LVMI、CVF、CTGF蛋白及mRNA表达均明显下降.光镜和电镜结果显示,辛伐他汀组心肌损害程度较模型组明显减轻.结论:辛伐他汀能显著改善慢性心力衰竭大鼠心肌肥厚,逆转心肌纤维化和超微结构的异常方面,其机制可能与下调CTGF的表达有关.     

大鼠心肌梗塞后心肌炎症反应和细胞因子表达

目的：探讨大鼠急性心肌梗塞(AMI)后是否存在心肌炎症反应和心脏细胞因子表达。方法：建立大鼠心梗模型并设假手术组，于术后第1、4、8周末测血流动力学后取心脏。RT-PCR检测心脏肿瘤坏死因子-α(TNF-α)、自介素(IL-1β、IL-6、IL-10)和转化生长因子-β(TGF-β)mRNA的表达，并进行心肌病理检查。结果：与假手术组相比，AMI组血流动力学有明显改变。术后第1周末梗塞区、交界区心肌炎性细胞浸润，同期发现梗塞区、交界区和非梗塞区细胞因子表达有不同程度增高，其中TGF-β升高最明显。梗塞后第4、8周末炎症细胞因子表达下降，但TGF-β仍高表达，梗塞区心肌纤维化。结论：炎症参与心肌梗塞后心室重塑，细胞因子在重塑中起一定作用，TGF-β扮演重要角色。     

卡托普利对实验性腹主动脉狭窄小鼠左心室肥厚的影响

目的 进一步证实实验性腹主动脉狭窄大鼠左心室肥厚及卡托普利的作用。方法 采用实验性腹主动脉银夹狭窄大鼠模型，观察左心室重量指数，放免测定血浆血管紧张素Ⅱ及左心室心肌局部ＡｎｇⅡ。结果 模型组ＬＶＭＩ，血浆ＡｎｇⅡ，左心室心肌ＡｎｇⅡ水平明显高于假手术组；卡托普利组ＬＶＭＩ，血浆ＡｎｇⅡ，左心室心肌ＡｎｇⅡ，左心室明显下降。     

左心室缺血再灌注肺损伤模型的建立

目的: 探讨建立左心室缺血再灌注肺损伤模型的方法。方法: 40只家兔随机分为模型组和对照组,模型组建立左心室缺血再灌注肺损伤模型,对照组不做模型。对比2组动物心电图、膈肌放电曲线、心肌和肺组织HE染色组织病理情况、肺组织透射电镜超微结构变化情况。结果: 模型组心肌出现缺血再灌注损伤表现,肺组织出现急性损伤表现,二者之间的变化呈相关性。结论: 此种左心室缺血再灌注肺损伤模型是一种可行可靠的动物模型。     

卡托普利对实验性腹主动脉狭窄大鼠左心室肥厚的影响

目的进一步证实实验性腹主动脉狭窄大鼠左心室肥厚及卡托普利的作用。方法采用实验性腹主动脉银夹狭窄大鼠模型,观察左心室重量指数（ＬＶＭＩ）,放免测定血浆血管紧张素Ⅱ（ＡｎｇⅢ）及左心室心肌局部 Ａｎｇ Ⅱ。结果模型组ＬＶＭＩ、血浆ＡｎｇⅡ、左心室心肌Ａｎｇ　Ⅱ水平明显高于假手术组;卡托普利组ＬＶＭＩ、血浆Ａｎｇ Ⅱ、左心室心肌Ａｎｇ　Ⅱ明显下降。结论使用腹主动脉银夹狭窄方法建立心脏后负荷增加的心肌肥厚动物模型是可靠的,卡托普利确有抗心肌肥厚的作用。     

实验性心肌肥厚大鼠血浆与心肌儿茶酚胺含量变化及黄芪的影响

结扎大鼠腹主动脉形成实验性心肌肥厚，对动物血浆及左心室组织中肾上腺素、去甲肾上腺素含量与心肌肥厚程度，以及黄芪注射液和卡托普利抗肥厚作用之间的相关性进行研究。手术4周后开始连续给药8周。以动物的心脏重量衡量心肌肥厚程度，用HPLC法测定血浆及左心室组织中肾上腺素和去甲肾上腺素含量，以SPSS统计软件对二者的相关性进行分析。结果显示模型组动物肾上腺素在血浆和心室组织中的含量均比对照组升高，去甲肾上腺素的血浆浓度比对照组升高，而其左心室组织中含量则低于对照组。黄芪注射液和卡托普利有不同程度的抗心肌肥厚作用，并可部分纠正肾上腺素和去甲肾上腺素含量的异常变化。相关性分析结果显示，心肌肥厚程度（全心重量、左心室重量）与左心室组织中去甲肾上腺素含量呈显著负相关性（P＜0．01）。上述结果提示：药物改变体内儿茶酚胺类物质含量可在一定程度上反映药物对心肌肥厚程度的影响。     

Captopril和Losartan对心肌梗塞大鼠心肌细胞核酸、蛋白质和胶原合成的影响

Ｃａｐｔｏｐｒｉｌ和Ｌｏｓａｒｔａｎ对心肌梗塞大鼠心肌细胞核酸、蛋白质和胶原合成的影响西安医科大学病理生理教研室（西安７１００６１）申景平，雷主权，高广道，李炯雌性ＳＤ大鼠随机分为假手术组（ＳＯ组），梗塞组（ＭＩ组），Ｃａｐｔｏｐｒｉｌ处理组（ＭＩ＋...     

兔心肌缺血再灌注损伤的超微结构变化及凋亡检测

目的　探讨实验性心肌缺血再灌注损伤时心肌超微结构变化及心肌细胞凋亡的发生。方法　选家兔 6只 ,阻断左冠状动脉的左室支建立心肌缺血模型 ,达到预定的缺血时间后 ,使血管再通 ,建立心肌的缺血再灌注模型。采用透射电镜、原位末端探针标记 (TUNEL)对不同损伤区心肌细胞的损伤情况进行研究。结果　电镜观察显示缺血再灌注损伤中心区呈现明显的心肌细胞凋亡征象 ,在缺血再灌注损伤交界区可见心肌细胞凋亡的早期征象 ,TUNEL检测结果显示缺血再灌注损伤中心区出现较多的凋亡阳性细胞 ,而损伤交界区出现较少的凋亡阳性细胞。结论　心肌细胞凋亡是心肌缺血再灌注损伤的重要特征 ,这与心肌的缺血性损伤存在不同     

Induction of Caspase Cascade as a Nonspecific Response to Myocardial Damage

In three experimental series, acute hemodynamic overload of the left ventricle, focal ischemia of the left ventricle, and diphtheritic intoxication were modeled in rabbits. On days 1, 3, and 5 of the experiments, activity of myocardial caspase-3 and caspase-8 were measured separately in the left and right ventricles. In the left ventricle, caspase-3 activity increased in all 3 modeled pathological processes, while in the right ventricle this parameter increased during acute overload and ischemic injury to the left ventricle. Caspase-8 activity increased only in the left ventricle during its hemodynamic overload and remained unchanged in other cases. It was concluded that induction of the caspase cascade can be considered as a nonspecific response to myocardial damage. In this case, specific mechanisms responsible for generation and transmission of apoptotic stimuli in cardiomyocytes have unique features.     

不同时段的心肌缺血后再灌注损伤与心肌细胞凋亡的实验研究

目的　探讨实验性不同时段的心肌缺血后再灌注损伤是否致心肌细胞凋亡、凋亡率的大小及不同的缺血时间与凋亡率的关系。方法　阻断左冠状动脉的左室支建立心肌缺血模型 ,达到预定的缺血时间后 ,使血管再通 ,建立心肌的缺血再灌注模型。采用透射电镜、原位末端探针标记、图像分析和统计处理对缺血灌注损伤区心肌细胞的损伤情况进行研究。结果　电镜观察和原位未端标记 (TUNEL)检测发现在经历了不同的缺血时间后 ,再灌注均可致心肌细胞凋亡 ,但不同的缺血时间后再灌注致心肌细胞的凋亡率不同 ,实验Ⅰ～Ⅲ组平均凋亡率分别为 3 2 7%、18 4 3%和 2 0 2 8%。缺血时间越长凋亡率越高。结论　心肌缺血再灌注损伤的发生与凋亡机制有关 ,且凋亡率的大小在一定的时间段内可能与心肌的缺血时间呈正相关     

Quantitative Three-Dimensional Wall Motion Analysis Predicts Ischemic Region Size and Location

Stress echocardiography is an important screening test for coronary artery disease. Currently, cardiologists rely on visual analysis of left ventricular (LV) wall motion abnormalities, which is subjective and qualitative. We previously used finite-element models of the regionally ischemic left ventricle to develop a wall motion measure, 3DFS, for predicting ischemic region size and location from real-time 3D echocardiography (RT3DE). The purpose of this study was to validate these methods against regional blood flow measurements during regional ischemia and to compare the accuracy of our methods to the current state of the art, visual scoring by trained cardiologists. We acquired RT3DE images during 20 brief (<2 min) coronary occlusions in dogs and determined ischemic region size and location by microsphere-based measurement of regional perfusion. We identified regions of abnormal wall motion using 3DFS and by blinded visual scoring. 3DFS predicted ischemic region size well (correlation r ² = 0.64 against microspheres, p < 0.0001), reducing error by more than half compared to visual scoring (8 ± 9% vs. 19 ± 14%, p < 0.05), while localizing the ischemic region with equal accuracy. We conclude that 3DFS is an objective, quantitative measure of wall motion that localizes acutely ischemic regions as accurately as wall motion scoring while providing superior quantification of ischemic region size.     

飞龙掌血水提物对心肌缺血兔心功能和血液动力学的影响

目的:观察飞龙掌血(Toddalia asiatica Lam)水提物(飞龙一号,F01)对急性心肌缺血动物模型心脏功能和血液动力学的影响。方法:新西兰兔作不开胸膜冠脉左前降支高位结扎造成急性心肌缺血, 观测结扎后及F01 ip对动物心功、血液动力学的影响。结果:冠脉左前降支结扎后,LVEDP显著升高(P＜0.05),t-dp/dt max 无明显变化,其余各项参数均明显降低(P＜0.05或P＜0.01)。F01(268 mg/kg)腹腔注射后,除有关左室作功和心肌耗氧的参数(HR、TTI和TTI×HR)继续降低外,其余各项参数的变化均显著逆转,恢复或接近结扎前的水平, 用药后1.5 h的作用较0.5 h更明显。结论:F01可显著减少急性缺血心肌的作功和耗氧,通过纠正心脏对氧的供需平衡失调,改善心脏收缩、舒张功能和泵血功能,从而发挥对缺血心肌的保护作用。     

Integrative Models for Understanding the Structural Basis of Regional Mechanical Dysfunction in Ischemic Myocardium

Myocardial ischemia and many other cardiac pathologies are associated with regional ventricular dysfunction. Since the distributions of stress and material properties cannot be measured directly in intact myocardium, understanding how regional alterations in myocardial strain or segment function are related to underlying cellular dysfunction must be deduced from theoretical models. Here, we describe how anatomically detailed, three-dimensional computational models can be used in conjunction with experimental or clinical studies to elucidate the structural basis of regional dysfunction in acutely ischemic and ischemic-reperfused (stunned) myocardium in vivo. Integrative experimental and computational analysis shows that: (1) in acutely ischemic myocardium, the transition from abnormal systolic strain in the ischemic region to normal shortening in adjacent, normally perfused tissue is governed primarily by systolic blood pressure and regional fiber orientation rather than the geometry of the perfusion boundary; and (2) in stunned myocardium, the degree of reperfusion injury to the contractile apparatus may be uniform across the wall thickness despite observations that the extent of ischemia and the impairment of regional strain during reperfusion are both significantly greater in the subendocardium. © 2000 Biomedical Engineering Society. PAC00: 8719Hh, 8719Uv, 8719Ff, 8719Rr, 8710+e     

External mechanical work from relaxing ventricle.

The possibility has been proposed earlier that the specific pressure-volume (P-V) area bounded by the left ventricular end-systolic and end-diastolic P-V curves and the isovolumic relaxation part of the P-V loop represents mechanical potential energy that has been built during systole and is stored at end systole in the wall of the ventricle. In the present study on canine left ventricles, as much as 70% of the P-V area was actually converted into external mechanical work when ventricular volume was allowed to decrease at an appropriate speed (about 55 ml/s in 70 g left ventricle) during relaxation. Less external work was extracted from the same P-V area when the speed of volume reduction was either higher or lower than that speed. These results indicate that the P-V area is equivalent to a form of potential energy, which is wasted with isovolumic relaxation but most of which is convertible to external mechanical work if the ventricle is allowed to eject against an appropriately decreasing afterload during relaxation.     

Clinical application of end-systolic pressure-volume relation

On the basis of a mathematical formalism derived in previous studies, properties of the end-systolic pressure-volume (P-V) relation were analyzed to define indexes that can characterize a normal or failing left ventricle. Careful analysis of different areas under the P-V line can lead to new indexes that describe the performance of the left ventricle. The possibility to distinguish between normal, midly depressed, or severely depressed left ventricles based on P-V relation is discussed. Implementation of the results for routine clinical work is examined.     

Left ventricular systolic pressure-volume area correlates with oxygen consumption.

In 13 excised, cross-circulated canine hearts, we studied the correlation between left ventricular oxygen consumption per beat (MVO2) and the magnitude of a specific pressure-volume (P-V) area circumscribed by the end-systolic and end-diastolic P-V relationship curves and the systolic segment of the P-V trajectory of a left ventricular contraction. The pressure and volume load of the ventricle were changed with a volume servo pump in order to alter the P-V area, and MVO2 was measured (after each change in the pressure and volume load). In the data collected from both isovolumic and ejecting contractions of each left ventricle contracting with a stable inotropic background, we found a linear correlation between MVO2 and the P-V area. The average correlation coefficient was 0.92 +/- 0.016 (SE). Linear regression analysis yielded the formula: MVO2 (ml/beat) = alpha[P-V area (mmHg.ml/beat)] + b, where alpha, the slope coefficient, was (1.53 +/- 0.14) x 10(-5) and b, which probably represents the basal O2 consumption, was 0.019 +/- 0.003 ml/beta. We propose that the P-V area as defined above may be a good index of ventricular oxygen consumption under a given inotropic background.