糖皮质激素受体激活对心肌细胞损伤后影响的实验研究

目的观察糖皮质激素受体(GR)激活对小鼠心梗(MI)后心功能和心肌细胞缺氧刺激的影响及其机制。方法将80只C57B/L6背景的野生雄性小鼠,按照随机数字表法随机分为生理盐水(盐水)组和地塞米松(地米)组,再分别分为假手术组和手术组(MI),即盐水+假手术组(20只)、地米+假手术组(20只)、盐水+MI组(20只)和地米+MI组(20只)。术前24h分别注入生理盐水(盐水)或地塞米松(地米,20 mg/kg),MI组结扎小鼠左冠状动脉前降支制作MI模型,假手术组只绕线不结扎,在术后第1、7天用小动物超声仪检测心功能指标;于术后1天取心脏组织行免疫组织化学染色及蛋白印迹法观察GR磷酸化水平、TUNEL染色观察细胞凋亡水平;于术后7天取心脏组织行Masson染色观察梗死面积、多因子试剂盒及实时荧光定量PCR检测脂联素蛋白和mRNA水平;并体外培养H9c2大鼠心肌细胞系,高内涵扫描实验观察地米对心肌细胞缺氧刺激后的凋亡和坏死的影响。结果与盐水+MI组比较,地米+MI组的磷酸化GR水平明显升高(1.75倍),小鼠MI后左室射血分数、舒张末期、收缩末期内径和短轴缩短率等心功能指标均明显改善(均为P<0.05),心脏损伤减轻,梗死面积减小(34.8%±5.8%比44.1%±3.6%,P<0.05),脂联素的蛋白(2.82倍)和mRNA(6.45倍)水平均明显升高(均为P<0.05),且凋亡细胞减少(P<0.05)。细胞实验显示与对照组相比,地米可显著减少缺氧刺激导致的H9c2心肌细胞凋亡和坏死(均为P<0.05)。结论 GR激活对小鼠MI后的心肌细胞损伤具有保护作用,这一作用可能与其抗炎和抗细胞凋亡、坏死作用有关。     

内脏脂肪组织传入神经阻断对心肌梗死后心脏功能和心脏神经重构的影响

目的 探讨内脏脂肪组织(VAT)传入神经阻断对心肌梗死(MI)后大鼠心脏功能及心脏神经重构的影响。方法 选择SPF级健康雄性SD大鼠30只,其中12只大鼠随机分为对照组和激活组,每组6只,激活组使用低浓度辣椒素(1 mmol/L)激活VAT传入神经,对照组注射等量生理盐水,监测实时血压心率30 min,计算激活前后血压及心率变化。另外18只大鼠随机分为假手术组、MI组、高浓度辣椒素阻断组(33 mmol/L),每组6只,采用结扎冠状动脉左前降支建立MI模型。MI造模成功后高浓度辣椒素阻断组使用高浓度辣椒素阻断VAT传入神经,假手术组和MI组注射等量生理盐水。2周后通过超声心动图测定心功能,氯化三苯四氮唑染色测定MI面积,检测心肌酪氨酸羟化酶(TH)密度。生化法检测心肌丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果 激活组大鼠血压及心率变化显著高于对照组,差异有统计学意义(P<0.01)。MI组大鼠MI面积、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、心肌TH密度、心肌MDA水平显著高于假手术组,左心室射血分数(LVEF)、心肌SOD水平显著低于假手术...     

一种快捷小鼠心肌梗死模型的建立

目的建立一种快速高效不需要通气辅助呼吸的小鼠心肌梗死模型制作方法,并对制作过程中的技巧细节进行分析。方法 40只C57/B6雄性小鼠,随机分成手术组(25只)和对照组(15只),于麻醉状态下在左侧第3,4肋间隙挤出心脏,手术组结扎冠状动脉左前降支建立小鼠心肌梗死模型;对照组不结扎冠状动脉,其余操作与手术组相同。28天后,心脏超声系统进行心功能测定对比,解剖进行形态对比和病理染色对比心肌梗死和纤维化。结果至术后第28天,手术组心肌梗死小鼠的生存率80%,对照组的小鼠生存率100%。超声检测显示28天后手术组小鼠心功能明显降低,与对照组相比,手术组心室明显扩大,左心室舒张期末内径由3.52±0.10 mm扩大到4.65±0.08 mm(P<0.0001),左心室收缩期末内径由2.60±0.19 mm扩大到4.36±0.13 mm(P<0.0001);左心室射血分数由66.70%±1.41%下降到29.70%±1.64%(P<0.0001),左心室缩短分数由35.90%±1.01%下降到14.20%±0.80%(P<0.0001)。肉眼可见手术组小鼠心脏左心室心腔变大,心室壁明显变薄,梗死面积可达45.10%±1.53%;HE、免疫组织化学、Masson病理染色可见有明显纤维瘢痕形成,有大量炎细胞浸润。结论此种方法制备心肌梗死模型高效快捷,动物死亡率低,结果明显,是一种较好的方法。     

慢性缺血性心力衰竭模型制备方法的对比研究

目的探讨冷冻左心室前壁与结扎前降支两种方法诱导大鼠心肌梗死后制作慢性心力衰竭模型的对比研究。方法选择8～10周龄SD健康大鼠120只,随机分为冷冻组(50只),结扎组(50只)、假手术组(20只)。手术后4周行心电图、心功能检查,取心脏组织行TTC、HE染色并观察其死亡率。结果手术后4周冷冻组大鼠死亡率为32%低于结扎组48%。与假手术组比较,冷冻组、结扎组大鼠心电图显示为心肌梗死,LVEF、左心室短轴缩短率明显降低,左心室舒张末直径明显升高,差异有统计学意义(P<0.01),冷冻组和结扎组大鼠心肌切片、TTC染色可见100%梗死区;梗死区HE染色主要为瘢痕组织,假手术组未见心肌梗死。结论冷冻法诱导的心力衰竭模型在心功能、心肌梗死面积等方面等同于结扎法,且死亡率明显减低,冷冻左心室前壁诱导大鼠心肌梗死后慢性心力衰竭模型较结扎法更好。     

肾去交感支配术对心肌梗死大鼠心功能和结缔组织生长因子的影响

目的探讨肾去交感支配术(renal sympathetic denervation,RSD)对心肌梗死(myocardial infarction,MI)大鼠心肌纤维化的影响及其可能机制。方法健康雄性SD大鼠54只,分为假手术(Sham组,10只)、RSD组(12只)、Sham 3d+MI组(16只)、RSD 3d+MI组(16只),观察期为MI术后4周。超声心动图评估大鼠心功能、RT-PCR法和蛋白印迹法分别评估大鼠左心室心肌组织中结缔组织生长因子(CTGF)mRNA和蛋白的表达水平。结果Sham 3d+MI组较Sham组和RSD组左心室收缩末内径和左心室舒张末容积水平明显增加(P0.01),左心室短缩率和LVEF水平明显降低(P0.01)。Sham 3d+MI组和RSD 3d+MI组大鼠心肌胶原容积分数[(59.13±6.00)%和(43.96±6.23)%vs(4.94±0.37)%和(4.19±0.59)%,P0.01]、CTGF mRNA相对表达(2.28±0.18和1.53±0.23 vs 0.80±0.11和0.71±0.07,P0.01)、CTGF蛋白相对表达(0.25±0.02和0.16±0.02 vs0.12±0.02和0.08±0.01,P0.01)较Sham组和RSD组明显增加,但RSD 3d+MI组大鼠心肌胶原容积分数、CTGF mRNA相对表达、CTGF蛋白相对表达水平较Sham 3d+MI组明显降低。结论 RSD术能改善MI大鼠心肌纤维化及心功能,可能与其下调致纤维化因子CTGF的表达有关。     

扩张型心肌病大鼠模型心肌结构与心功能的变化

目的探讨扩张型心肌病大鼠胶原重塑及其与心功能的关系.方法用呋喃唑酮饲养Wistar大鼠建立扩张型心肌病(DCM)大鼠模型, 超声心动图检测大鼠左心室舒张期末内径(LVED)、左心室收缩期末内径(LVES)、左心室内径缩短率(FS)及左心室射血分数(LVEF);右心导管测压,HE染色观察大鼠心肌细胞形态学变化;VG和免疫组化染色检测心肌胶原纤维及胶原容积分数(CVF).结果①与正常对照组相比,DCM组大鼠心脏LVED(cm)和LVES(cm)均明显增大、FS(%)和LVEF(%)均明显下降,左心室内径增大、游离壁变薄,心脏重量/体重比值增加,右房压明显增高(均P>0.05).②DCM大鼠心肌细胞肥大,变性,间质胶原纤维明显增多,间质胶原CVF及Ⅰ、Ⅲ型胶原的含量明显增加.结论 DCM大鼠心肌间质胶原网络重塑影响左室功能.     

扩张型心肌病大鼠模型心肌结构与心功能的变化

目的　探讨扩张型心肌病大鼠胶原重塑及其与心功能的关系。方法 用呋喃唑酮饲养Wistar大鼠建立扩张型心肌病(DCM)大鼠模型, 超声心动图检测大鼠左心室舒张期末内径(LVED)、左心室收缩期末内径(LVES)、左心室内径缩短率(FS)及左心室射血分数(LVEF);右心导管测压,HE染色观察大鼠心肌细胞形态学变化;VG和免疫组化染色检测心肌胶原纤维及胶原容积分数(CVF)。结果 ①与正常对照组相比,DCM组大鼠心脏 LVED(cm)和 LVES(cm)均明显增大、FS(%)和LVEF(%)均明显下降,左心室内径增大、游离壁变薄,心脏重量/体重比值增加,右房压明显增高(均P>0 .05)。②DCM大鼠心肌细胞肥大,变性,间质胶原纤维明显增多,间质胶原 CVF及Ⅰ、Ⅲ型胶原的含量明显增加。结论 DCM大鼠心肌间质胶原网络重塑影响左室功能。     

辛二酰苯胺异羟肟酸通过抑制组蛋白去乙酰化酶改善小鼠心肌肥厚的研究

目的:探讨组蛋白去乙酰化酶(HDAC)抑制剂辛二酰苯胺异羟肟酸(SAHA)改善小鼠心肌肥厚的作用,为防治心肌肥厚提供新思路。方法:选取60只昆明小鼠,随机分为正常组、假手术组、心肌肥厚组、心肌肥厚+SAHA组,通过部分结扎小鼠胸主动脉建立心肌肥厚模型,最终每组纳入6只。采用苏木素伊红(HE)染色观察小鼠心肌细胞,超声心动图检测小鼠心功能,比色法检测HDAC活性,小鼠心肌组织中HDAC亚型HDAC5和β-肌球蛋白重链(β-MHC)信使核糖核酸(mRNA)和蛋白表达水平分别运用逆转录-聚合酶链反应(RT-PCR)和蛋白免疫印迹(Western blot)检测。结果:HE染色结果表明心肌肥厚组小鼠心肌细胞肥大、排列紊乱、细胞核深染。心肌肥厚组小鼠左心室舒张末期直径、左心室舒张末期容积均显著低于假手术组(P0.05),而室间隔明显较假手术组增厚(P0.05)。心肌肥厚组小鼠HDACs活性显著高于假手术组(P0.05);心肌肥厚组HDAC5和β-MHC的mRNA及蛋白表达水平均显著高于假手术组(P0.05)。SAHA能够显著降低HDAC5表达水平,显著下调心脏肥厚相关基因β-MHC的表达并改善小鼠心功能和心肌肥厚(P均0.05)。结论:HDAC参与了心肌肥厚的发生,HDAC抑制剂SAHA通过抑制HDAC5的表达从而改善小鼠心肌肥厚。     

应用压力-容积环评价曲美他嗪对大鼠心肌顿抑的影响

目的应用压力-容积环评价曲美他嗪对大鼠心肌顿抑的影响及可能机制。方法 30只雄性SD大鼠,随机等分成3组:对照组、心肌顿抑组(生理盐水2 mL)和曲美他嗪组(曲美他嗪片3 mg/kg)。结扎冠状动脉左前降支20 min再灌注120 min,制作大鼠心肌顿抑模型(对照组只穿线不结扎)。用压力-容积系统动态观察心率、左心室收缩期末压、收缩期末压力容积、左心室舒张期末压及舒张期末压力容积等血流动力学变量以及压力-容积环变化,并应用软件PowerLab系统离线分析;再灌注结束后测定大鼠心肌组织中ATP含量、ATP酶活性及磷酸果糖激酶活性,并应用体视学方法定量分析大鼠心肌线粒体的变化。结果与心肌顿抑组相比,曲美他嗪组舒张期末压、收缩期末容积、前负荷补充搏功均显著降低(P<0.01),舒张期末压力-容积也降低(P<0.05);舒张期末容积、收缩期末压力容积均显著升高(P<0.01),ATP含量及ATP酶(Ca2+-Mg2+ATPase和Na+-K+ATPase)活性增加(P<0.05);磷酸果糖激酶活性显著增加(P<0.01);心肌线粒体损伤显著减轻(P<0.01)。结论曲美他嗪可以通过改善能量代谢降低心肌顿抑的发生,压力-容积环能准确敏感地评价心功能。     

抑制1-磷酸鞘氨醇裂解酶活性加重缺血性心力衰竭

目的:观察1-磷酸鞘氨醇(S1P)裂解酶(SPL)在小鼠缺血性心衰(HF)模型中的作用。方法:将60只成年雄性C57/BL6J小鼠随机分为以下4组:假手术(Sham)组、心肌梗死(MI)组、假手术+THI(Sham+THI)组[THI是SPL的抑制剂]及MI+THI组,每组15只(n=15),将25 mg/L THI溶于饮水中,于手术24 h后连续饲喂2周。MI4周后,采用ELISA试剂盒测定心肌中S1P的含量。根据心脏质量/体质量(HW/BW)评价心肌肥厚。用小动物心脏超声评估小鼠心脏结构和功能,经Masson三色染剂染色法观察心脏纤维化。用Western blot检测转化生长因子-β(TGF-β)蛋白的表达。实时PCR检测Ⅰ、Ⅲ型胶原、心房钠尿肽(ANP)、脑钠尿肽(BNP)和平滑肌肌动蛋白-α(α-SMA)mRNA的水平。结果:与MI组相比,MI+THI组小鼠心肌组织中S1P的含量增加(P0.01);左心室射血分数(LVEF)降低(P0.01),左心室收缩末期内径(LVESD)和舒张末期内径(LVEDD)均增加(均P0.05),HW/BW增加(P0.01),心脏纤维化加重;TGF-β蛋白的表达增加(P0.01);Ⅰ、Ⅲ型胶原、ANP、BNP和α-SMA mRNA的水平均显著增加(均P0.01)。与Sham组相比,Sham+THI组小鼠上述指标无显著差异。结论:抑制SPL的活性可能增加梗死后心肌病理性S1P信号的激活,加重MI后的心脏重构和HF。     

The cardiac component of cardiac cachexia

Background Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. Methods Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 ± 13 vs 67 ± 8 years, P = .07; New York Heart Association class 2.9 ± 0.7 vs 2.6 ± 0.6, P = .08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. Results Cardiac dimensions including LV diastolic (69 ± 9 mm vs 67 ± 13 mm) and systolic cavity diameter (58 ± 11 mm vs 55 ± 15 mm), LV mass (480 ± 180 g vs 495 ± 190 g), and LV systolic and diastolic function including fractional shortening (16% ± 10% vs 18% ± 10%), isovolumic relaxation time (29 ± 22 ms vs 36 ± 27 ms), and E/A ratio (2.7 ± 1.6 vs 3.3 ± 2.9) did not differ between cachectic and noncachectic patients (all P > .1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (χ² test, P < .05). Conclusions Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia. (Am Heart J 2002;144:45-50.)     

Analysis of cardiac symptoms preceding cardiac arrest

Prodromal symptoms and cardiac history were examined in 227 patients with coronary artery disease who were successfully resuscitated after out-of-hospital cardiac arrest. Cardiac arrest was sudden—with either no symptoms or symptoms for less than 1 hour—in 71% of the patients. Nonsudden death—death occurring after more than 1 hour of symptoms—occurred in 29% of the patients. A history of cardiovascular disease was present in 85% of patients with sudden cardiac arrest and in 83% with nonsudden arrest. Cardiac arrest occurred without symptoms in 38% of the patients with sudden cardiac arrest and was the first expression of coronary artery disease in 4% of the entire study group. This study indicates that cardiac arrest usually occurs with symptoms and almost always in the setting of a history of cardiovascular disease.     

心脏骤停和心脏性猝死

心脏性猝死(SCD)是目前社会关注的热点问题.2005年WHO的数据表明,在全球死于心脑血管疾病的约1700万人群中,40%～50%是SCD.SCD虽然有多种定义,但目前一般认为是在1 h内出现的由于心血管原因导致的非预期死亡事件或无目击者的死亡事件.心脏骤停(SCA)不等同于SCD,SCA如果救治失败会引起真正的SCD.     

Sodium-induced cardiac aldosterone synthesis causes cardiac hypertrophy

High sodium intake causes cardiac hypertrophy independently of increases in blood pressure. Aldosterone is synthesized in extraadrenal tissues such as blood vessels, brain, and heart. Effects of 8 weeks of high sodium intake on cardiac aldosterone synthesis, as well as cardiac structure, mass, and aldosterone production, levels of mRNA coding for aldosterone synthase (CYP11B2) and the angiotensin II AT1 receptor, were studied in normotensive Wistar-Kyoto (WKY) rats. Isolated rat hearts were perfused for 2 hr, and the perfusate was analyzed by high-performance liquid chromatography and mass spectrometry. Aldosterone synthase activity was estimated from the conversion of [14C]deoxycorticosterone to [14C]aldosterone. Levels of mRNA for CYP11B2 and AT1 receptor were determined by competitive polymerase chain reactions. A high sodium intake for 8 weeks produced left ventricular hypertrophy without elevation of blood pressure. Plasma aldosterone concentrations and plasma renin concentrations were decreased by high sodium intake. Aldosterone production, activity of aldosterone synthase, and expression of mRNA for CYP11B2 and AT1 receptor were increased in hearts of rats with high sodium intake. These results suggest that high sodium intake increases cardiac aldosterone synthesis, which may contribute to cardiac hypertrophy independently of the circulating renin-angiotensin-aldosterone system.     

Occult cardiac lymphoma presenting with cardiac tamponade

Subxiphoid pericardiostomy is the procedure of choice for treatment of a pericardial effusion with tamponade. We report a case in which this procedure not only failed to reveal the presence of an occult malignancy, but also resulted in a recurrent symptomatic effusion.     

External cardiac pacing during in-hospital cardiac arrest

External noninvasive cardiac pacing offers a rapid and simple method of pacing the heart during an emergency. It has been suggested that early use of cardiac pacing for bradycardia or asystole may improve survival in patients who have cardiac arrest. To investigate this possibility 58 consecutive episodes of cardiac arrest occurring on the medical wards or emergency room. Twenty-six episodes underwent external noninvasive pacing for bradycardia or asystole refractory to standard drugs. Only 2 patients survived, and survival could be directly attributed to pacing in only 1 of them. Of the 32 episodes not undergoing pacing, 23 had transient asystole or bradycardia, 13 of which rapidly responded to medications. The 17 cases (53%) not undergoing pacing survived. In conclusion, when bradycardia or asystole during cardiac arrest fails to respond to standard pharmacologic measures, it is an indicator of severe myocardial damage, and attempts at cardiac pacing rarely improve survival.     

Acute cardiac tamponade due to cardiac actinomycosis

Cardiac actinomycosis occurs in less than 2 percent of the patients with infections due to Actinomyces israelii. We describe the findings in a patient with acute cardiac tamponade who survived through pericardial drainage and aggressive medical therapy. Although uncommon, this disorder is important to recognize because it is curable with current medical and surgical therapy.     

Coronary angioscopy during cardiac catheterization and cardiac surgery

Summary Coronary angioscopy (CA) was performed in 30 patients (pts) during cardiac catheterization (Group 1) and in 11 pts during coronary bypass surgery (Group 2) using ultrathin fiberoptic angioscopes (Ø1.2–1.8 mm). For percutaneous CA (Group 1) the angioscope was introduced through a 9F guiding catheter from the femoral artery. The viewing field was cleared by flushing Ringer's solution and short-time occlusion of the coronary ostium by the guiding catheter. In Group 2 CA was performed retrogradely from the distal arteriotomy and through the bypass vein during flushing with cardioplegic solution. In Group 1 in 17/30 pts the coronary artery could be successfully examined by CA. In 13 pts the obstruction was eccentric and irregular shaped. In 2/5 pts, in whom CA was performed successfully pre and post balloon dilatation, CA after PTCA revealed an intimal rupture without clinical or angiographical signs of the intimal dissection. In Group 2 in 9/11 pts good visualization of stenoses could be achieved. At the obstruction site CA revealed thrombi in 3 pts and ulcer in 1 pts. In contrast to angiography, which estimates the lumen diameter of a segmental lesion, CA gives information about the luminal shape and the underlying substance of the obstruction (e.g. atheroma, thrombus, ulceration). The main problems in percutaneous CA are the insufficient intraluminal guidance, the insufficient depth of view of the angioscopes, and the limited examination time.     

心脏介入性治疗并发心脏压塞的处理策略

目的 探讨心脏介入治疗并发心脏压塞的处理策略。方法 12例心脏压塞患者，男性5例，女性7例，年龄28～52岁。其中经皮二尖瓣球囊扩张术8例，冠状动脉腔内成形术1例，先天性动脉导管未闭封堵术2例，右心室起搏1例。根据心脏穿孔的不同原因、可能的部位及心脏压塞情况，分别采用心包穿刺引流、心包穿刺引流与开胸修补或开胸置管引流等方法治疗。结果 3例单纯心包穿刺引流均痊愈；8例紧急心包穿刺引流后开胸修补有7例痊愈，1例主动脉根部破裂者因心源性休克时间过长，死于呼吸衰竭；1例冠状动脉腔内成形术者左回旋支穿孔，紧急心包穿刺引流后心包切开、胸腔置管引流痊愈。结论 根据心脏介入性治疗导致心脏压塞的不同原因、可能部位及心脏压塞进展情况，采取相应措施，可有效治疗此类并发症。