Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg^–1 in two animalsand 0.6 µg. kg^–1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin the control group (0.58± 0.38 vs 3.42 ± 0.84),in contrast to nearly baseline values in the experimental group(0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.     

一种新的大鼠冠状动脉微栓塞模型

目的 建立一种新的大鼠冠状动脉微栓塞模型。方法 48只大鼠随机分为模型组、假手术组和正常对照组,每组16只。钳夹升主动脉后自主动脉根部注入自身血栓微粒0.2ml/只,24h后取心脏标本,染色计数被栓塞的小冠脉数量;28d后染色计算胶原纤维占心肌组织面积的百分比。结果①HE染色显示,模型组被栓塞的小冠脉数量明显多于假手术组,分别为(31.88±3.80)％、(1.50±0.93)％(P<0.01);而假手术组和正常对照组差异无统计学意义(P>0.05)。②Martius—Sarlet—Blue染色显示,模型组被栓塞的小冠状动脉数量明显多于假手术组,分别为(32.38±3.81)％、(1.38±0.92)％(P<0.01);而假手术组和正常对照组差异无统计学意义(P>0.05)。③Sirius-Red染色显示模型组胶原纤维面积百分比明显大于假手术组,分别为(6.51±1.22)％、(1.08±0.19)％(P<0.01);而假手术组和正常对照组差异无统计学意义(P>0.05)。结论 自身血栓微粒能稳定的造成大鼠冠状动脉微栓塞,该模型可作为冠状动脉微栓塞病理生理学研究较理想的实验平台。     

TNFα in ischemia/reperfusion injury and heart failure

Abstract. During myocardial ischemia, both the myocardial and serum TNF concentrations are rapidly increased within the area at risk. With prolongation of ischemia and development of cardiomyocyte necrosis, the TNF concentration increases also in the surrounding viable portions of the myocardium. Indeed, in the scenario of myocardial ischemia/reperfusion, treatment with TNF antibodies reduced the extent of myocardial infarction in rabbits and attenuated the contractile dysfunction following microembolization in dogs. In the latter studies, the serum TNF concentration remained unaltered thereby supporting the notion of a direct action of TNF at the level of cardiomyocytes during ischemia/reperfusion.In heart failure, the serum TNF concentration is also increased, and in patients with advanced heart failure the serum TNF concentration is an independent predictor of mortality. The origin of the increased serum TNF concentration is not clearly identied yet, but TNF derived from the heart and peripheral organs contributes to the increased serum TNF concentration. Treatment with TNF antibodies in the clinical scenario, however, did not improve the prognosis of heart failure patients.     

不同剂量卡维地洛对大鼠冠状动脉微栓塞后心室重塑的影响

目的:比较不同剂量卡维地洛对大鼠冠状动脉微栓塞(CME)后心室重塑的影响.方法:利用大鼠自体的血栓微粒造成心肌内小冠状动脉栓塞,建立CME模型.40只大鼠随机分成4组,即假手术组(SO组)、CME组、小剂量卡维地洛组(LCAR组,1.0 mg*kg-1*d-1)和大剂量卡维地洛组(HCAR组,10.0 mg*kg-1*d-1).灌胃4周后,行心功能检测、血流动力学测定及心肌病理学分析.结果:与SO组比较,CME组细胞间质胶原容积分数(CVF)与心肌细胞凋亡率(Rapo)明显增加,左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)明显增大,左心室短轴缩短率 (LVFS)、左心室射血分数 (LVEF)明显降低(均P<0.01);左心室舒张末期压(LVEDP)明显增加,左心室收缩压(LVSP)和左心室腔内压力最大上升速率(+LVdp/dtmax)显著下降(均P<0.01).与CME组比较,LCAR组和HCAR组心肌间质CVF和Rapo显著降低,LVEDD、LVESD明显减小,LVFS明显上升,LVEF明显改善(均P<0.01);LVEDP明显下降,+LVdp/dtmax显著上升,心率明显减慢(均P<0.01).除LVSP外,以上改变HCAR组均较LCAR组明显(P<0.05).结论:①大鼠CME后心脏发生慢性重塑;②卡维地洛剂量依赖性地改善CME后心室重塑.     

猪冠状动脉微栓塞致心肌梗死模型的建立

目的 以聚乙烯醇(PVA)为栓塞剂, 采用经皮微导管介入方法建立可长期存活的猪冠状动脉微栓塞(CME)致心肌梗死模型。方法 对16只西藏小型猪经股动脉选择性插管, 于左前降支动脉第一对角支开口处远端缓慢注入不同浓度100 μm PVA, 于术后第3天、第60天行640层容积CT心肌灌注成像;动物处死后对心肌组织行TTC染色和病理学观察。结果 9只动物造模成功并长期存活, 其PVA浓度为0.001 ml/ml, 注射总量10 ml;CT心肌灌注成像示左心室心尖前壁、侧壁及间隔壁灌注缺损, 主要位于心内膜下, 部分累及心外膜下心肌;心脏TTC染色和病理示微血管栓塞区域心肌梗死。结论 以PVA颗粒为栓子, 采用经皮微导管介入方法建立猪CME致心肌梗死模型成功率高、存活时间长, 为临床研究CME致心肌梗死的理想动物模型。     

冠状动脉内直接支架植入对冠状动脉微循环的影响

目的探讨选择性冠状动脉病变不作球囊预扩张的直接支架植入术对冠状动脉微循环的影响。方法选择急性冠状动脉综合征（ACS）92例，随机分为直接支架植入A组（47例）和球囊预扩张后支架植入B组（45例），选择的病变均为A型或B1型病变，以造影剂心肌染色（TMP）分级法、TIMI计帧法和支架植入术前后心肌酶的变化作为心肌组织灌注成功和冠状动脉微循环栓塞形成的诊断标准。结果（D两组支架植入成功率均为100％。②TMP分级：A组TMP3级34例（72％），B组TMP3级21例（47％），两组间有显著性差异（P〈0.05）。③TIMI帧数：A组支架植入前后TIMI帧数虽有增加，但无统计学差异（P〉0．05）；B组支架植入前后TIMI帧数明显增加，有统计学意义（P〈0．05）；两组间术后增加的TIMI帧数比较，B组比A组增加明显，有统计学差异（P〈0．05）。④心肌酶学变化：A组术前术后比较无统计学意义（P〉0．05），B组术前术后变化有统计学意义（P〈0．05），两组之间比较有统计学明显差异（P〈0．001）。结论冠状动脉（A型或B1型病变）内直接支架植入，冠状动脉微循环栓塞的发生率低，心肌组织血流灌注程度高。     

Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of dogs

Purpose We investigated the effects of propofol on contractility and oxygen balance in acute ischemic myocardium and compared them with those of normal myocardium using a coronary microembolization model in dogs.Methods In open-chest dogs, the left anterior descending coronary artery (LAD) was perfused through an extracorporeal bypass from the carotid artery. Regional myocardial contractility and myocardial oxygen balance were evaluated along with segment shortening (%SS), regional myocardial oxygen consumption (MVO₂), and lactate extraction ratio (LER) of the area perfused by the LAD. Acute ischemia was produced by repeated injection of microspheres into the LAD-perfused area until %SS decreased by 50% of baseline.Results In normal myocardium, intracoronary infusion of propofol at doses of 1.2 and 2.4mg·kg^–1·h^–1 caused slight decreases in %SS to 83% ± 8% and 80% ± 10%, respectively. In ischemic myocardium, propofol caused greater decreases in %SS (59% ± 18% and 35% ± 20%, respectively). The changes in MVO₂ after propofol infusion generally paralleled the changes in %SS, but LER was not changed in either ischemic or normal myocardium.Conclusion Propofol causes a greater decrease in the contractility of acute ischemic myocardium as compared with normal myocardium in which myocardial oxygen imbalance is not involved as a mechanism.     

Hemodynamic Changes in a Model of Chronic Heart Failure Induced by Multiple Sequential Coronary Microembolization in Sheep

Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 ± 2 kg), chronic heart failure was induced under flouroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 µm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3‐week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan‐Ganz catheter (mean pulmonary arterial pressure [PAPmean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre‐ and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 ± 4 bpm [base] to 93 ± 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 ± 5 [base] to 38 ± 7 [3 mo][P < 0.05]), and increased body weight 77 ± 2 kg to 81 ± 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.