可溶性ST-2对接受阿霉素化疗乳腺癌患者的左心功能及结构变化预测价值的研究

目的通过检测乳腺癌患者接受阿霉素化疗后的可溶性致癌抑制因子2(sST-2)水平以及心脏功能指标,评估sST-2水平对左心功能损害的预测价值。方法回顾性收集2016年9月至2018年6月期间于郑州大学第五附属医院乳腺外科接受阿霉素(吡柔比星)化疗的90例乳腺癌患者的临床病理资料。所有患者均于化疗前以及接受蒽环类化疗药物治疗1年时抽取外周静脉血血样检测sST-2水平和心功能指标,同时行超声心动图检查。结果与化疗前比较,化疗1年时的sST-2、左心室收缩末期容积(left ventricular end-systolic volume,LVESV)、左心室舒张末期容积(left ventricular end diastolic volume,LVEDV)、左心室收缩末期内径(left ventricular systolic diameter,LVESD)、左心室舒张末期内径(left ventricular diastolic internal diameter,LVEDD)和二尖瓣舒张早期血流峰值速度与二尖瓣环舒张早期运动峰值速度比值(E/e’)升高,LVEF值降低,差异均有统计学意义(P<0.05)。sST-2水平与LVEF值存在负相关关系(r=–0.618,P<0.05)。受试者工作特征曲线结果显示,sST-2水平为11.9 ng/mL时为最佳临界值,以此预测左心室功能损害的灵敏度和特异度分别为90.6%和69.2%,ROC曲线下面积为0.836(P<0.05)。结论 sST-2对预测接受阿霉素类化疗的乳腺癌患者的左心功能有一定的辅助诊断价值。     

三维斑点追踪成像评估化疗致卵巢癌患者左心室功能损伤

目的观察三维斑点追踪成像(3D-STI)评估紫杉醇联合卡铂对卵巢癌患者左心室功能影响的价值。方法对30例卵巢癌术后接受紫杉醇联合卡铂化学治疗(简称化疗)患者(卵巢癌组)分别于化疗前及化疗3、6周期后行3D-STI检查,以同期30名正常女性为对照组,获取左心室射血分数(LVEF)、左心室整体纵向应变(GLS)、圆周应变(GCS)、左心室扭转角度(LVtw)、扭矩(Tor)及纵向与圆周应变显像舒张指数(L-SI-DI、C-SI-DI),计算心肌综合指数(MCI)。采用受试者工作特征(ROC)曲线评价3D-STI参数对化疗致左心室收缩功能损害的诊断效能。结果卵巢癌组化疗前LVEF、GLS、GCS、LVtw、Tor、MCI、L-SI-DI及C-SI-DI与对照组差异均无统计学意义(P均>0.05),化疗3、6周期后上述参数均较对照组及化疗前降低,且化疗6周期后下降更显著(P均<0.05)。GLS、LVtw、Tor及MCI诊断化疗致左心室收缩功能损伤的AUC均>0.800(P均<0.05),其敏感度、特异度均>60.00%,约登指数均>0.50;其中MCI的AUC最大(0.907),Tor的敏感度最高(86.67%),GLS特异度最高(90.00%)。结论3D-STI可早期发现并量化评价紫杉醇联合卡铂化疗所致卵巢癌患者左心室功能损伤。     

实时三维超声检测心肌节段参数评价风湿性二尖瓣狭窄的左心室运动

目的应用实时三维超声心动图(RT-3DE)检测左心室心肌节段参数,评估风湿性二尖瓣狭窄患者左心室心肌各节段运动功能。方法回顾性分析2014年10~11月我院14例风湿性二尖瓣狭窄(RMS)患者的临床资料(试验组),其中男4例、女10例,年龄34~64(50.9±9.0)岁;另选择健康人员11名作为对照组,其中男7名、女4名,年龄32~67(49.5±9.7)岁。2组患者均行常规二维超声(2DE)及实时三维超声(RT-3DE)检查,记录左心室射血分数(LVEF)、左心室舒张期末容积(LVEDV)、左心室收缩期末容积(LVESV)、左心室心肌各节段的纵向应变值、圆周应变值、面积应变值、横向应变值。结果两组RT-3DE检测的LVEF、LVEDV、LVESV试验组较对照组明显减小(P0.05),左心室心肌纵向应变试验组较对照组大部分节段有明显减小(P0.05)。结论通过RT-3DE可准确评价风湿性二尖瓣患者心肌运动及功能的变化。     

心肌带结构在常用心脏超声切面的分布

目的 初步观察心肌带(ventricular myocardial band,VMB)结构在常用心脏超声切面的分布情况.方法 成年猪心、牛心和羊心各5个,按照VMB的标准解剖方法将心脏解剖为完整的VMB结构,将VMB各段按标准分界后用油性染料着色,自然凉干后还原为未解剖前状态.将已染色的还原VMB按常用心脏超声切面切开,显示各个平面上VMB各段的分布情况.结果 清楚地显示了VMB各段在不同平面中的分布情况,其中左心室在不同平面中显示由2～3层心肌构成,而右心室则仅由1层心肌构成.结论 在不同的常用心脏超声切面中,心肌带各段的分布情况不尽相同,为今后使用心脏超声进一步深入研究心肌带结构和功能打下了一定基础.     

脓毒症大鼠心功能及氧化应激水平变化

目的观察脓毒症大鼠超声心动图、心肌组织病理学表现及氧化应激水平变化。方法将48只12周龄SD大鼠随机均分为脓毒症24 h组(CLP24 h组)、脓毒症48 h组(CLP48 h组)、假手术组(Sham组)及空白对照组(Blank组)。造模后采用彩色多普勒超声测量各组左心室舒张末期内径(LVEDD)、室间隔舒张末期厚度(IVSD)、左心室后壁舒张末期厚度(LVPWD)、左心室短轴缩短率(LVFS)、左心室射血分数(LVEF)及心率(HR)。对心肌组织行HE及Masson染色,观察心肌组织病理学变化。测定心肌组织超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)及丙二醛(MDA)水平,并分析其与LVEF的相关性。结果 4组LVIDD、IVSD、LVFS、LVEF及HR差异均有统计学意义(P均0.01), LVFS、LVEF及HR在Blank组Sham组CLP24 hCLP48 h组。CLP24 h组及48 h组部分心肌细胞肿胀坏死,心肌间隙中胶原纤维明显增多,48 h组更显著。SOD、GSH在Blank组Sham组CLP24 hCLP48 h组,MDA在Blank组Sham组CLP24 h组CLP48 h组。LVEF与SOD、GSH呈正相关(r=0.922 6、0.938 0,P均0.001),与MDA呈负相关(r=-0.929 8,P0.001)。结论脓毒症可引起大鼠心功能异常及心脏结构改变;氧化应激可能是脓毒症致心肌损害的重要机制。     

骨髓间充质干细胞自体移植治疗心肌梗死的实验研究

目的探讨兔骨髓间充质干细胞(MSCs)移植至缺血心肌后的增殖分化情况,对缺血心肌细胞的修复重建能力及心功能改善情况。方法将20只新西兰白兔随机分为骨髓间充质干细胞移植组(MSCs组,n=10)和对照组(n=10),采用结扎冠状动脉左前降支(LAD)制备心肌梗死模型,2周后分别将Dil标记的1×106个细胞悬液400μl或等量L-DMEM培养基用微量注射器注入梗死灶边缘,于建模前、建模后2周、细胞移植后2、4周采用多普勒超声心动图检测左心室收缩期末内径(LVESD)、左心室舒张期末内径(LVEDD),计算左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)评价心脏收缩功能,同时进行心肌声学造影评价心肌组织的血流灌注情况。细胞移植后8周处死所有动物,病理学检查移植细胞在梗死区的生长状况。结果多普勒超声心动图检测结果显示:两组动物建模前、建模后2周LVEF、LVFS差异无统计学意义(0.72±0.08vs.0.71±0.04,0.56±0.11vs.0.55±0.09;0.35±0.06vs.0.35±0.04,0.24±0.08vs.0.23±0.03,P>0.05),细胞移植后2、4周MSCs组LVEF、LVFS值均明显高于对照组(0.71±0.05vs.0.60±0.05,0.72±0.07vs.0.62±0.08;0.34±0.03vs.0.29±0.01,0.35±0.06vs.0.27±0.05,P<0.05);病理学检查见自体MSCs移植8周后存活于梗死心肌中,表达肌细胞特异性标志,并且能显著增加瘢痕区毛细血管密度(38.6±7.6/mm2vs.21.4±3.9/mm2,P<0.05),心肌声学造影亦显示梗死局部血流灌注MSCs组较对照组明显改善。结论自体MSCs移植缺血心肌中可向心肌细胞分化,增加心肌血流灌注,改善心脏收缩功能。     

实时三维超声心动图评价心肌致密化不全患儿左心室收缩功能

目的探讨实时三维超声心动图(RT-3DE)评价心肌致密化不全患儿左心室整体及局部收缩功能的价值。方法依据常规超声左心室射血分数(LVEF)将34例LVNC患儿分为LVEF正常组(A组,LVEF≥50%,25例)及LVEF减低组(B组,LVEF50%,9例),选取同期20名健康儿童作为正常对照组(C组),行RT-3DE检查,测量左心室收缩末期容积(LVESV)、左心室舒张末期容积(LVEDV)及LVEF,计算收缩末期左心室最厚处非致密心肌/致密心肌比值(NC/C)并观察左心室17节段心肌受累情况,通过左心室容积-时间曲线分析获得节段舒张末期容积(rEDV)、节段收缩末期容积(rESV)及节段射血分数(rEF),并进行统计分析。结果与C组比较,A组LVEDV(t=-0.17,P=0.87)、LVESV(t=0.79,P=0.44)及LVEF(t=-1.72,P=0.10)差异均无统计学意义;B组LVEDV(t=1.62,P=0.15)差异亦无统计学意义,但LVESV明显增大(t=2.85,P=0.03),且LVEF明显减低(t=-6.15,P0.01)。A组NC/C与B组间差异无统计学意义(t=-1.15,P=0.27),但左心室心肌受累节段数更少(t=-4.59,P=0.03)。A组与C组间左心室17节段rEDV及rESV差异均无统计学意义(P均0.05),左心室中部后间隔、后壁及后侧壁、心尖部间隔、下壁及侧壁rEF差异均有统计学意义(P均0.05)。B组均与C组间左心室17节段rEDV差异无统计学意义(P均0.05),基底部后侧壁及前侧壁、中部前壁、前间隔、后壁、后侧壁及前侧壁、心尖部前壁、间隔及侧壁rESV、左心室17节段rEF差异均有统计学意义(P均0.05)。结论应用RT-3DE技术评估LVNC患儿整体和局部收缩功能有利于早期诊断、治疗和改善预后。     

斑点追踪成像技术评价表阿霉素对乳腺癌患者左心室心肌纵向分层应变的影响

目的探讨二维斑点追踪成像(2D-STI)分层应变技术评价表阿霉素(Epi)对左心室各层心肌纵向收缩功能影响的价值。方法 140例乳腺癌术后患者,分为3组:A组,40例,平均年龄(52.1±6.1)岁,未给予化疗;B组,50例,平均年龄(50.9±7.3)岁,化疗方案为环磷酰胺+Epi+5-氟尿嘧啶,Epi累积剂量180~240 mg/m2;C组,50例,平均年龄(54.4±7.4)岁,与B组化疗方案相同,Epi累积剂量≥360mg/m2。分别获取患者左心室心尖位四腔、二腔切面、左心室长轴切面二维图像,并测定各层心肌的纵向应变峰值(LS)及常规超声参数。结果 3组患者心肌常规超声心动图参数差异无统计学意义(P0.05);A、B、C组的LS至内向外逐层递减,即:心内膜下心肌中层心肌心外膜下心肌;3组间心外膜下心肌、中层心肌LS差异无统计学意义(P0.05);A组与B组心内膜下心肌LS差异无统计学意义(P0.05),C组与A组心内膜下心肌LS、C组与B组心内膜下心肌LS差异有统计学意义(P0.05)。结论 2D-STI心肌纵向分层应变可精确反映Epi对各层心肌的浸润程度,其影响主要在心内膜层。     

主动脉瓣重度狭窄伴左心室收缩功能受损患者的外科疗效分析

目的分析主动脉瓣置换术在治疗主动脉瓣重度狭窄伴左心室收缩功能受损患者中的疗效。方法回顾性分析2000年1月至2011年12月在第二军医大学长海医院接受手术治疗的主动脉瓣重度狭窄伴左心室收缩功能受损[左心室射血分数（LVEF）〈50％]患者的临床资料,排除二尖瓣狭窄患者。共纳入29例患者,男22例、女7例,年龄14～76（56.3±12．9）岁。将患者手术前后临床及心脏超声心动图相关指标进行比较,评价手术效果,并根据患者LVEF恢复情况,分析可能影响患者术后心脏功能恢复的危险因素。结果术后早期死亡1例。其余28例患者术后主动脉瓣跨瓣压差由（97．6±25．1）mmHg降至（25．0±9．7）mmHg,LVEF由41％±6％增加至56％±11％,左心室舒张／收缩期末直径／容积均较术前明显改善（P均〈0．001）。结论主动脉瓣膜置换术是主动脉瓣重度狭窄伴左心室收缩功能受损患者的有效治疗方法,术后左心室超声指标显著改善。术前左心室扩大程度较低可能更利于术后LVEF的恢复。     

晚期肾病患者心肌二维超声心动图的变化

心血管疾病是晚期肾病(ESRD)患者常见的致死原因,其中95％伴有心脏大小和功能异常改变。超声心动图检查心脏变化最有价值。作者报道了ESRD患者的超声心动图特征。方法对1982～1986年间在Tulane医疗中心做过超声心动图的全部ESRD患者进行回顾性分析。包括年龄、种族、性别、透析时间、肾移植时间、原发肾脏病、高血压病史,检测血红蛋白、血清肌酐、钙、磷水平。所有患者均做M型和二维超声心动图,检查左心室末期舒张直径、左心房大小、室间隔厚度和左心室后壁厚度,按美国超声心动图协会建议的统计方法进行分析。同时检查有无二尖瓣和二尖瓣环钙化,有无主动脉硬化和心包积液。用Troy-Pombo公式计算左心室量和量指数。特别注意心肌的构造,在2个心室寻找有无反射回声增强,如果存在则称心肌有“闪光花斑现象(GSA)”将有GSA的患者归入Ⅰ组,无GSA者为Ⅱ组。结果 59(男33,女26)例ESRD患者的超声心动图表明,41例(69％)在心肌肥大,20例     

Perioperative assessment of diastolic dysfunction

Assessment of diastolic function should be a component of a comprehensive perioperative transesophageal echocardiographic examination. Abnormal diastolic function exists in >50% of patients presenting for cardiac and high-risk noncardiac surgery, and has been shown to be an independent predictor of adverse postoperative outcome. Normalcy of systolic function in 50% of patients with congestive heart failure implicates diastolic dysfunction as the probable etiology. Comprehensive evaluation of diastolic function requires the use of various, load-dependent Doppler techniques This is further complicated by the additional effects of dehydration and anesthetic drugs on myocardial relaxation and compliance as assessed by these Doppler measures. The availability of more sophisticated Doppler techniques, e.g., Doppler tissue imaging and flow propagation velocity, makes it possible to interrogate left ventricular diastolic function with greater precision, analyze specific stages of diastole, and to differentiate abnormalities of relaxation from compliance. Additionally, various Doppler-derived ratios can be used to estimate left ventricular filling pressures. The varying hemodynamic environment of the operating room mandates modification of the diagnostic algorithms used for ambulatory cardiac patients when left ventricular diastolic function is evaluated with transesophageal echocardiography in anesthetized surgical patients.     

‘Conditioning’ the heart during surgery

Coronary heart disease (CHD) is the leading cause of death worldwide. Coronary artery bypass graft (CABG) surgery remains the procedure of choice for coronary artery revascularisation in a large number of patients with severe CHD. However, the profile of patients undergoing CABG surgery is changing with increasingly higher-risk patients being operated upon, resulting in significant morbidity and mortality in this patient group. Myocardial injury sustained during cardiac surgery, most of which can be attributed to acute myocardial ischaemia–reperfusion injury, is associated with worse short-term and long-term clinical outcomes. Clearly, new treatment strategies are required to protect the heart during cardiac surgery in terms of reducing myocardial injury and preserving left ventricular systolic function, such that clinical outcomes can be improved. ‘Conditioning’ the heart to harness its endogenous cardioprotective capabilities using either brief ischaemia or pharmacological agents, provides a potentially novel approach to myocardial protection during cardiac surgery, and is the subject of this review article.     

Early changes and rules of cardiac function and hemodynamics in rabbits with experimental myocardial contusion

Objective: To study changes and rules of the left ventricular functions in rabbits with myocardial contusion through parallel functional analysis by using echocardiography combined with cardiac catheter intervention. Methods : Thirty healthy rabbits were selected and impacted to make moderate or severe myocardial contusion by BIM-Ⅱ biomedical impact machine. The changes of bemodynamics and cardiac systolic and diastolic functions were respe~vely observed before injury and 1, 4, 8 and 24 hours after injury. Results: After myocardial contusion, the heart rate,systolic pressure, diastolic pressure and mean arterial pressure of rabbits decreased remarkably at 1-4 hours. The left ventricular end-systolic pressure ( LVESP ), the maximum increasing rate of the left intraventricular pressure ( dp/dtmax), isovolumic pressure (IP) and the maximum systolic vdocity of the left ventricle (Vmax) also decreased markedly. And then these parameters recovered to the levd of preinjury at 8-24 hours. The left ventricular end-diastolic pressure (LVEDP), the rate of the left intraventricular pressure ( - dp/dtmax ) and the decreasing time constant of the left intraventricular pressure (T) increased remarkably 1 hour after myocardial contusion,and did not decrease until 8 hours after myocardial contusion. Detection by echocardiography showed that ejection fraction of the left ventricle markedly decreased at 24 hours after myocardial contusion, while the systolic volume decreased obviously as early as 1 hour after myocardial contusion, at 4-8 hours it recovered a little and again decreased at 24 hours. The end systolic volume and end diastolic volume increased after myocardial contusion,but statistical sitmificance was only seen at 8 hours after myocardial contusion. Conclusions: Cardiac functions of the left and right ventricles are markedly injured after myocardial contusion with disorders of the left ventricle diabolic function and of the right ventricle systolic function as the dominant injury.While the systolic function of the left ventricle can recover.Echocardiography shows clinical importance in detection of early injuries of cardiac functions.     

Clinical Evidence of Myocardial Stunning in Patients Undergoing CABG Surgery

Abstract Although patients who have undergone coronary artery bypass graft (CABG) surgery frequently present with symptoms suggesting that myocardial stunning has occurred, measurements of regional myocardial function and perfusion are difficult in clinical settings. Several studies have used left ventricular function indices (i.e., cardiac index, left ventricular stroke work index, ejection fraction) to assess myocardial stunning immediately following CABG surgery. These changes in ventricular function have been found to be reversible and the clinical data are consistent with the occurrence of myocardial stunning. Myocardial metabolism is also reportedly depressed following CABG surgery. Decreases in myocardial oxygen extraction, consumption, and lactate utilization all point to the presence of myocardial stunning, as do abnormalities in regional wall-motion and electrocardiographic changes (i.e., transient Q waves) described in patients who have undergone CABG surgery. New approaches to differentiating viable from nonviable myocardial tissue will likely include stress echocardiography using new stress agents, ultrasound contrast agents, and high frequency ultrasound.     

Coronary artery bypass grafting in patients with poor left ventricular function using retrograde continuous cold blood cardioplegia]

Patients with poor left ventricular function or those requiring urgent surgery may have more extensive ischemic myocardial injury if myocardial preservation is incomplete. We have performed coronary artery bypass grafting (CABG) aimed at complete revascularization in such cases using RC-CBCP, which is considered more effective on myocardial preservation during aortic cross-clamping in particular to protect ischemic area distal to severe coronary artery stenosis or obstruction. In the present study, in 25 patients with poor left ventricular function (left ventricular ejection fraction; LVEF less than or equal to 0.3) including 10 patients who required urgent surgery, the operative results were evaluated. All the distal and proximal anastomoses of grafts (average 2.5 grafts) were completed during one aortic cross-clamping using RC-CBCP, therefore graft flow was obtained immediately after release of the aortic clamping. Though this method required 142 minutes of a mean aortic cross-clamping time, myocardial protection was considered to be preferable judging from postoperative isoenzymatic evaluation and improved ventricular function. Fifteen patients with elective CABG were all alive and restored to NYHA class I to II. Among 10 patients requiring urgent CABG, 4 patients with acute myocardial infarction died but others were restored to NYHA class I to II. We conclude that it is important to aim at complete coronary revascularization in patients with poor left ventricular function and RC-CBCP achieves more effective myocardial protection during CABG in the patients.     

Evaluation of native left ventricular function during mechanical circulatory support: theoretical basis and clinical limitations.

Left ventricular function on patients with heart disease is now evaluated by echocardiography, but these dimensional changes are erroneous in the patient supported by left ventricular assist device because of mechanical unloading for the failing heart. Left ventricular end-systolic pressure-volume relationship provides theoretically most reliable left ventricular contractility. Recently, some patients have weaned from the device because of unexpected recovery of myocardial contractility. But it is very important to evaluate the left ventricular function just before the weaning, and to predict the longevity of the recovered function to keep the good quality of life. Current clinical situation in the patients with ventricular assist device, and theoretical limitations to evaluate the recovering myocardium are discussed.     

Protection against oxygen-induced reperfusion injury of the isolated canine heart by superoxide dismutase and catalase

While oxygen-derived free radicals have been implicated in the pathogenesis of myocardial injury, the exact nature of this injury is still unclear. To test the hypothesis that oxygen-induced injury may influence the recovery of cardiac function from ischemic damage, we used an oxygen free radical scavenger, superoxide dismutase (SOD), together with catalase, during the reperfusion of isolated canine heart which had been subjected to 15 min of normothermic ischemic arrest followed by 2 hr of hypothermic cardioplegic preservation using a modified Collins solution. Determinations of thiobarbituric acid reactive substances and coenzyme Q10 within the myocardium showed that the treatment with SOD and catalase was capable of inhibiting lipid peroxidation induced by reperfusion. This inhibition was apparently associated with the improvement of myocardial energy metabolism and cardiac performance. Coronary flow was significantly higher in the heart treated with SOD and catalase during the working stage with a corresponding increase in oxygen consumption. Myocardial adenosine triphosphate (ATP) was partially, but significantly restored during reperfusion in these hearts whereas no restoration was observed in the heart without the enzymes. The treatment with SOD and catalase also improved left ventricular stroke work index and left ventricular maximum dp/dt at an early stage of the working mode. These results suggest that the use of SOD and catalase during reperfusion can protect the ischemic heart against reperfusion injury by scavenging oxygen-derived free radicals.     

Extended Evaluation of Effects of Anoxia on Ventricular Performance and Compliance

Eight dogs were prepared by implanting a left ventricular pressure transducer, aortic flow probe, and endocardial ultrasound crystals across the maximum transverse left ventricular diameter. In an unanesthetized state, the dogs were evaluated at rest and with acute volume loading, both before ischemic cardiac arrest and sequentially (2, 4, 6, 12, 24, and 48 hours) after 20 minutes of arrest during normothermic cardiopulmonary bypass.At a left ventricular end-diastolic diameter comparable to preoperative levels, left ventricular systolic pressure, heart rate, and rate of rise of left ventricular pressure were not changed, but at 2 to 6 hours there was a significant decrease in cardiac output (p < 0.01), left ventricular stroke work (p < 0.01), ejection fraction (p < 0.05), maximum rate of systolic diameter shortening (p < 0.05), and circumferential fiber shortening (p < 0.05). They gradually returned to control levels by 24 hours postoperatively. Left ventricular compliance, as measured by left ventricular end-diastolic pressure at a set end-diastolic diameter and by left ventricular diastolic pressure/diameter, was reduced at 2 hours (p < 0.01) and gradually returned to control values at 48 hours. Thus, reversible myocardial injury due to anoxia is associated with both decreased contractility and compliance, with resultant depressed left ventricular performance for 24 to 48 hours after injury.     

Novel cardioprotective effects of tetrahydrobiopterin after anoxia and reoxygenation: Identifying cellular targets for pharmacologic manipulation

OBJECTIVES: Contemporary cardioprotective strategies to prevent perioperative ischemia-reperfusion injury have focused on the l-arginine nitric oxide pathway. Tetrahydrobiopterin is an absolute cofactor required for the enzyme nitric oxide synthase and is thus a critical determinant of nitric oxide production. We hypothesized that ischemia-reperfusion results in diminished levels of tetrahydrobiopterin, which might represent a key cellular defect underlying endothelial and myocyte dysfunction after ischemia-reperfusion. To this aim, we examined the effects of tetrahydrobiopterin supplementation in (1) an in vivo experimental model of global ischemia-reperfusion and (2) an in vitro human ventricular heart cell model of simulated ischemia-reperfusion. Measures of endothelial function, oxidant production, cell survival, and cardiac function were used to assess outcome. METHODS: In study 1 Wistar rats were divided into one of 2 groups (n = 10 per group). One group received tetrahydrobiopterin (25 mg x kg(-1) x d(-1) for 7 days), and the other group served as the control group. Hearts were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion, and left ventricular developed pressure, left ventricular systolic pressure, and left ventricular end-diastolic pressure were determined by using the modified Langendorff technique. In study 2 we quantitated myocardial malondialdehyde, a marker of lipid peroxidation, in ventricular tissues from both groups of animals using butanol phase extraction and spectrophotometric analysis. In study 3 coronary vascular responses were determined in vascular segments of the left coronary artery in both groups of animals after ischemia-reperfusion. Endothelium-dependent and endothelium-independent vasodilatation to acetylcholine and sodium nitroprusside, respectively, were compared between groups. In study 4, using a human ventricular heart cell model of simulated ischemia-reperfusion, we studied the effects of tetrahydrobiopterin (20 micromol/L) on cellular injury (as assessed by means of trypan blue uptake). RESULTS: After ischemia-reperfusion, myocardial dysfunction was evidenced by a decrease in left ventricular developed pressure and an increase in left ventricular end-diastolic pressure (P =.01 compared with baseline). Hearts from tetrahydrobiopterin-treated rats exhibited protection against ischemia-reperfusion injury (left ventricular developed pressure: 74 +/- 4 vs control 42 +/- 8 mm Hg, P =.01; left ventricular end-diastolic pressure: 12 +/- 3 vs 34 +/- 7 mm Hg, P =.01). Furthermore, tetrahydrobiopterin treatment attenuated the rise in malondialdehyde levels after ischemia-reperfusion (P =.01). After reperfusion, coronary endothelial function to acetylcholine was attenuated (P =.003 vs sham-treated mice), whereas responses to sodium nitroprusside remained unchanged. Tetrahydrobiopterin-treated rats exhibited an improvement in acetylcholine-mediated vasorelaxation (P =.01 vs ischemia-reperfusion group). Cellular injury, as assessed by means of trypan blue uptake, was higher in human ventricular heart cells subjected to simulated ischemia-reperfusion; this effect was prevented with tetrahydrobiopterin treatment (P =.001). CONCLUSIONS: Supplemental tetrahydrobiopterin provides a novel cardioprotective effect on left ventricular function, endothelial-vascular reactivity, oxidative damage, and cardiomyocyte injury after ischemia-reperfusion injury and might represent an important cellular target for future operative myocardial protection strategies.     

Chirurgische Therapie linksventrikulärer Aneurysmata

Due to the development of postinfarction left ventricular aneurysms, kinetic dysfunction, left ventricular thrombus formation, arrhythmia and heart failure can occur. Surgical resection of ventricular aneurysms is the only effective therapy so far to stop the remodeling process, recreate the geometry of the ventricle and to improve ventricular function. Several techniques of reconstruction exist but most frequently used is the modified technique of Dor. The advantages of this technique are that all parts of the aneurysms can be excluded and a new apex can be reconstructed. Other surgical treatments are the technique of Cooley and the linear resection with or without patch plasty. Several studies demonstrate that, with definite indications, patients with postinfarction left ventricular aneurysms benefit from surgical treatment.