Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction

To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.     

交感神经刺激对大鼠缺血性室性心律失常的影响及其机制的探讨

目的 探讨大鼠急性心肌缺血时交感神经刺激对室性心律失常的影响及其潜在的机制.方法 结扎大鼠冠状动脉前降支制备急性心肌缺血模型后随机分组作为心肌缺血组(MI组,n=25)、缺血+交感神经刺激组(MI-SS组,n=25)、交感神经刺激+酚妥拉明+缺血组(MI-SS-Phen组,n=15)、交感神经刺激+普萘洛尔+缺血组(MI-SS-Prop组,n=15)和假手术组(SO组,n=20).心电图监测室性心律失常的发生.蛋白免疫印记法(Western blot)检测缝隙连接蛋白43(Cx43)的磷酸化蛋白及总量表达变化.逆转录聚合酶链反应(PCR)分析Cx43 mRNA的表达变化.免疫荧光观察Cx43表达分布情况.结果 结扎冠状动脉30 min内MI、MI-SS和MI-SS-Phen组分别有1、3和2只大鼠死于心室颤动(室颤);MI-SS组室性心动过速(室速)/室颤发生率(80.0%,20/25)较MI组(52.0%,13/25)明显增加(P＜0.05);与MI-SS组相比,普萘洛尔明显阻断了交感神经刺激促室速/室颤发生的作用(13.3%,2/15,P＜0.05).冠状动脉结扎30 min后,MI组磷酸化Cx43的比例较SO组显著降低(P＜0.05),但其总量并未减少(P＞0.05).与MI组相比,MI-SS组磷酸化Cx43的比例明显增加(P＜0.05),同时其蛋白总量的表达显著降低(P＜0.05);普萘洛尔显著抑制了交感神经刺激导致的Cx43蛋白降解的作用,同时抑制了缺血引起的Cx43脱磷酸化(P＜0.05).MI和MI-SS组Cx43mRNA表达均较SO组显著减少(P＜0.05).免疫荧光结果 显示,与SO组相比,MI组Cx43由端-端连接转化为侧-侧连接,而MI-SS组Cx43分布明显紊乱,不能分辨出Cx43的分布模式.结论 交感神经刺激能够促进室性心律失常的发生,可能主要与β肾上腺素受体的激活从而促进了Cx43的降解有关.     

Comparison of the influence of acute transmural and nontransmural myocardial infarction on ventricular function

In order to assess the relative impact on left and right ventricular function of nontransmural and transmural acute myocardial infarction (AMI), we performed radionuclide ventriculography in 86 patients (54 men and 32 women) within 16 hours after a first infarct. Nontransmural infarction was present in 19 patients (11 anterior and 8 inferior). Transmural infarction was found in 67 patients (30 anterior and 37 inferior). Left ventricular ejection fractions were higher (0.57 +/- .014 vs 0.46 +/- 0.14, p less than 0.005) and left ventricular end-systolic volume lower (29 +/- 11 vs 42 +/- 20 ml/m2, p = 0.013) in patients with nontransmural infarction compared to those with transmural infarction. Right ventricular ejection fraction also may have been different in the two groups (0.63 +/- 0.15 vs 0.55 +/- 0.13, p = 0.057). In patients with inferior infarction, left and right ventricular ejection fractions were similar in patients with nontransmural and transmural infarction (0.60 +/- 0.09 vs 0.55 +/- 0.10, p = 0.119 and 0.58 +/- 0.14 vs 0.51 +/- 12, p = 0.226). On the other hand, patients with anterior transmural infarction had lower left ventricular ejection fractions (0.36 +/- 0.12 vs 0.54 +/- 0.17, p = 0.003) but similar right ventricular ejection fractions (0.60 +/- 0.13 vs 0.66 +/- 0.14, p = 0.14) compared to those with nontransmural anterior infarction. In 29 additional patients with a history of previous infarction, no differences in any of the parameters studied were found between those with transmural and those with nontransmural infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical significance of transmural versus nontransmural electrocardiographic changes in patients with acute myocardial infarction

Two hundred thirty patients with probable or definite acute myocardial infarction were observed in a coronary care unit. The electrocardiogram showed changes in the S-T segment and T wave associated with a definitely abnormal enzyme curve in 45 patients (group I), with minimal enzyme rises in 33 patients (group II) and with development of Q waves and evolutionary changes in the S-T segment and T wave in 152 patients (group III). The incidence of supraventricular arrhythmias, ventricular premature beats and primary ventricular tachycardia was similar in all groups. The incidence of shock and mortality rates was similar in groups I (22 and 37 per cent, respectively) and III (18 and 19 per cent, respectively) and significantly greater when compared with group II (3 and 3 per cent, respectively) (p <0.05). There was a significant increase (p <0.05) in maximal serum lactic dehydrogenase (LDH) and serum glutamic oxaloacetic transaminase (SGOT) in patients with severe pump failure when compared to those in patients who had no or mild congestive heart failure. The incidence of severe pump failure and mortality is closely reflected in the magnitude of the enzyme rise but not in the electrocardiographic changes. Although a subset of patients with acute myocardial infarction in whom the prognosis was excellent (group II) was identified, the hazard of arrhythmic deaths (judged by the incidence of premature ventricular contractions and ventricular tachycardia) was similar in all groups.     

Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias

BACKGROUND: Small scale clinical trials suggested the feasibility and the efficacy of autologous myoblast transplantation to improve ventricular function after myocardial infarction. However, these trials were hampered by unexpected episodes of life-threatening ventricular tachyarrhythmias (VT). We investigated cardiac electrical stability after myoblast transplantation to the myocardium. METHODS AND RESULTS: Seven days after coronary ligation, Wistar rats were randomized into 3 groups: a control group receiving no further treatment, a vehicle group injected with culture medium into the infarcted myocardium, and a myoblast group injected with autologous myoblasts. Holter monitoring did not discriminate the myoblast from the vehicle groups. Programmed Electrical Stimulation (PES) was performed to evaluate further a cardiac substrate for arrhythmia susceptibility. The occurrence of sustained VT during PES was similar in control and vehicle groups (5/17 and 4/19 rats, respectively; p=0.50). In contrast, 13/20 rats (65%) from the myoblast group showed at least one episode of sustained VT during PES (p<0.05 and p<0.005 versus control and vehicle groups). As a further control group, rats injected with autologous bone marrow mononuclear cells into the infarcted myocardium did not show increased susceptibility to PES. CONCLUSIONS: In an infarcted rat model, myoblast transplantation but not bone marrow mononuclear cells or myocardial injection per se induces electrical ventricular instability. Because ventricular arrhythmias are life-threatening disorders, we suggest that such preclinical evaluation should be conducted for any new source of cells to be injected into the myocardium.     

Coronary angiography and left ventriculography in survivors of transmural and nontransmural myocardial infarction

Recent studies have suggested a similar prognosis for patients with transmural myocardial infarction and nontransmural myocardial infarction despite a smaller infarct size in the latter patients estimated by creatine phosphokinase (CPK). Thirty-one patients with transmural myocardial infarction and 17 patients with nontransmural myocardial infarction as defined by electrocardiographic criteria underwent coronary angiography and left ventriculography from 10 to 24 days after they had an acute myocardial infarction. Forty-three of these 48 patients were asymptomatic following their myocardial infarction. When compared to patients with nontransmural myocardial infarction, those with transmural myocardial infarction had greater peak CPK levels, 1,090 +/- 210 versus 290 +/- 60 IU (p less than 0.01). There was no difference in prevalence of single, double or triple vessel coronary artery disease, mean number of coronary arteries 50 per cent narrowed (2.0 +/- 0.2 versus 2.0 +/- 0.2), near total or total occlusions, coronary score (Friesinger) (7.9 +/- 0.6 versus 8.2 +/- 0.7), left ventricular ejection fraction (48 +/- 2 versus 53 +/- 4), or per cent of akinetic-dyskinetic myocardial segments (66 of 242 [27 per cent] versus 32 of 132 [24 per cent]) between two groups. The similar extent of coronary artery narrowing and degree of left ventricular dysfunction may explain the similar prognosis for patients with transmural myocardial infarction and those with nontransmural myocardial infarction despite differences in enzymatically estimated acute infarct size.     

Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats

Background

Mesenchymal stem cell transplantation is a promising new therapy to improve cardiac function after myocardial infarction (MI). The electrophysiological consequences of MSC implantation has not been systematically studied.

Methods

We investigated the electrophysiological and arrhythmogenic effects of mesenchymal stem cells (MSCs) therapy in experimental infarction model. Rats were subjected to MI operation by LAD ligation and randomly allocated to receive intramyocardially injection PBS (MI-PBS) or 5 × 10⁵ EGFP labeled MSCs (MI-MSCs). Electrophysiological study, histological examination, and western blotting were performed 2 weeks after cell transplantation.

Results

Programmed electrical stimulation (PES) showed a significant reduced inducible ventricular tachycardias (VTs), raised ventricular fibrillation threshold (VFT) and prolonged ventricular effective refractory period (VERP) in MSC-treated rats compared to PBS-treated animals. MSC implantation led to markedly longer action potential duration (APD) and shorter activation time (AT) in infarcted border zone (IBZ) of left ventricular epicardium compared with PBS-treated hearts. Histological study revealed that fibrotic area and collagen deposition in infarcted region were significantly lower in MI-MSC group than in MI-PBS group. Abnormal alterations of Connexin 43 including reduction and lateralization were significantly attenuated by MSC treatment.

Conclusions

This study provide strong evidence that MSC implantation ameliorates interstitial fibrosis and the remodeling of gap junction, attenuates focal heterogeneity of reporlarization and conduction and reduces vulnerability to VTs. The results suggest that MSC transplantation might emerge as a new preventive strategy against VAs besides improving cardiac performance in ischemic heart disease.     

Patterns of activation in ventricular arrhythmias of late myocardial infarction in dogs

Ventricular arrhythmias were produced in 12 dogs 4 to 6 days after coronary artery ligation by programmed ventricular stimulation. The electrocardiogram and 7 composite electrograms from endocardial and epicardial surfaces of the ischemic, border and normal zones, as well as from the right ventricle, were recorded during and after programmed ventricular stimulation. The ventricular arrhythmias were preceded and sustained by delayed, fragmented activity in the ischemic epicardial zone bridging diastole. Efferent pathways from the ischemic epicardium led to direct epicardial spread to adjacent normal epicardium in most instances. Efferent pathways into the endocardial regions were also observed, but to a lesser extent. The efferent reentry pathways led to both ventricles, and produced right and left ventricular arrhythmias in 8 of the 12 dogs; they were exclusively of left ventricular origin in the remaining 5. Classification of right and left ventricular arrhythmias may only be related to the exit points and not necessarily to their origin.     

选择性去心脏交感传入神经对犬急性心肌梗死后室性心律失常的影响

目的探讨选择性去心脏交感传入神经(SCSAD)对犬急性心肌梗死(AMI)后自主神经功能、心室电生理特性和室性心律失常的影响。方法 24只成年雄性杂种犬随机分为对照组(n=8)、AMI组(n=8)和SCSAD组(n=8)。SCSAD组犬心外膜给予树胶脂毒素。对照组和AMI组犬心外膜涂抹不含树胶脂毒素的溶剂。AMI组与SCSAD组通过结扎冠状动脉(简称冠脉)左前降支建立AMI模型,对照组只分离穿线,不结扎冠脉。于结扎冠脉后15 min检测心率变异性(HRV),记录结扎后1 h室性心律失常的发生情况,对照组于相应时间点检测。ELISA法检测血清去甲肾上腺素(NE)水平。于结扎冠脉后1 h依次采用S_1S_2程控刺激测量心室有效不应期(ERP),S_1S_1 300 ms起搏测量单相动作电位(MAP)和S_1S_1动态起搏法测量动作电位时程(APD)电交替起搏周长。通过不同电压直接电刺激左侧星状神经节(LSG)后的最大收缩压变化百分比评价LSG功能。蛋白免疫印记法(Western blot)检测各组新鲜LSG组织的c-fos和神经生长因子(NGF)的表达。结果与对照组相比,AMI组HRV明显降低,SCSAD组较对照组和AMI组升高。相比对照组,AMI组和SCSAD组室性早搏发生增多,而SCSAD组较AMI组减少。与AMI组相比,SCSAD组室性心动过速发生减少,且SCSAD组与对照组相比无差异。与对照组相比,AMI组和SCSAD组血清NE水平升高,SCSAD组较AMI组低。与对照组相比,AMI组结扎后其缺血区心室ERP和MAP缩短,APD电交替起搏周长延长。SCSAD组较AMI组ERP和MAP延长,APD电交替起搏周长缩短,且SCSAD组较对照组ERP延长,MAP和APD电交替起搏周长无差异。AMI组LSG功能比对照组增强,SCSAD组较对照组和AMI组LSG功能减低。AMI组c-fos表达比对照组高,NGF表达二者无明显差异,而SCSAD组c-fos和NGF表达比AMI组低。结论 SCSAD降低AMI后心脏交感神经活性,提高心脏电生理稳定性,减少室性心律失常的发生。     

R and S wave changes produced by experimental nontransmural and transmural myocardial infarction

Electrocardiographic R and S wave changes occur after transmural myocardial infarction. It was the purpose of this study to define the spatial characteristics of these changes and their pathologic determinants after nontransmural as well as transmural necrosis. Twenty-six dogs were studied after occlusion of the left circumflex coronary artery for 60 to 240 minutes, followed by reperfusion. Electrocardiographic potentials were recorded before and 1 week after infarction using an 84 electrode array to compute maximal and root-mean-square R and S wave voltages. Infarct size was quantitated by computer-aided evaluation of heart slices stained by triphenyltetrazolium chloride. R and S wave amplitudes after infarction varied widely from one torso site to another in a pattern generally consistent with the inferoposterior location of the infarcted zones. Although changes in peak R and S wave potentials did not significantly correlate with infarct size, differences in pre- and postocclusion root-mean-square R and S wave amplitudes did, with correlation coefficients of -0.79 and -0.63, respectively. Root-mean-square values increased for small lesions and decreased for larger ones. These data indicate that nontransmural as well as transmural infarction can produce R and S wave changes that are dependent on overall lesion size and the specific lead studied. Such changes may represent useful methods to quantitate lesion size.     

Prophylactic versus selective lidocaine for early ventricular arrhythmias of myocardial infarction

A total of 333 patients arriving within 6 h of the onset of suspected or proven but uncomplicated myocardial infarction were randomized to treatment by either the prophylactic or the selective lidocaine strategy. Patients were monitored for 24 h. The major end points were sustained ventricular tachycardia or fibrillation and emergent adverse effects of lidocaine. There were four episodes of emergent adverse effects of lidocaine, all in patients treated by the prophylactic strategy (2.4%, p = NS). There were two episodes of nonagonal, sustained ventricular tachycardia or fibrillation, both in patients treated by the selective strategy (1.2%, p = NS). The difference between major end points was 1.2% in favor of the selective strategy (p = NS). There were significant differences in lesser ventricular arrhythmias and lesser lidocaine adverse effects but no difference in mortality rate (selective = 3%, prophylactic = 5%, p = NS). Potentially lethal ventricular arrhythmias occurred only in patients with myocardial infarction. Nonlethal but complex ventricular arrhythmias were rare in patients without infarction. However, toxicity occurred in patients with and without infarction. The major conclusion of this study is that there is no important overall advantage of either strategy for lidocaine use in such patients. The advantage of one is the risk of the other. The strategy used should be selected for individual patients, and the use of one strategy for all patients would seem inappropriate.     

白藜芦醇降低大鼠心肌梗死后室性心律失常的研究

目的:探讨白藜芦醇对大鼠心肌梗死(myocardial infarction,MI)后室性心律失常的影响及可能机制。方法:将成功建立心肌梗死模型的24只SD大鼠随机分为MI组(n=12)和白藜芦醇组(n=12),另设假手术组(n=12),其中白藜芦醇组给予白藜芦醇10 mg/(kg·d)灌胃,MI组和假手术组给予5%羧甲基纤维素钠灌胃。4周后,所有大鼠行电生理检查;ELISA法检测血清白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α水平;免疫组化和Western blot检测心肌缝隙连接蛋白43(Cx43)表达水平。结果:与假手术组相比,MI组室性心律失常的诱发率明显增加,心室颤动阈值显著降低,血清IL-1β、TNF-α水平明显增加,Cx43表达水平显著降低(P0.05);与MI组相比,白藜芦醇组心律失常诱发率显著降低,心室颤动阈值增加,血清IL-1β、TNF-α水平明显降低,Cx43表达明显增加(P0.05),但白藜芦醇不能使上述指标恢复到假手术组水平(P0.05)。结论:白藜芦醇可有效降低大鼠心肌梗死后室性心律失常的发生,其机制可能与提高心肌Cx43表达,降低炎症反应有关。     

肾去交感神经对心肌梗死犬室性心律失常及心室电不稳定性的影响

目的:探讨肾去交感神经(RSD)对心肌梗死(MI)后早期室性心律失常及慢性期心室电不稳定性的影响。方法:21只杂种犬随机分成假手术组、MI组和RSD组,每组各7只,通过结扎冠状动脉前降支制作MI模型。造模成功1 h后,利用程序刺激检测梗死边缘区及远离梗死区的心室有效不应期(VERP),RSD组行双侧肾动脉交感神经射频消融术,假手术组和MI组仅行肾动脉造影,持续体表心电图记录1 h,观察各组室性心律失常发生率和持续时间;1周后重复检测上述部位的VERP,最后测定所有存活动物的心室颤动阈值(VFT)。结果:仅MI组有2只犬发生自发性心室颤动而死亡,RSD组室性心律失常的发生率和持续时间明显低于MI组(P0.05);MI 1 h后,3组动物的梗死边缘区及远离梗死区的VERP无明显差异;MI 1周后,RSD组梗死边缘区VERP、VFT较MI组均得到明显改善(P0.05),而与假手术组无明显差异。结论:RSD可以抑制MI早期室性心律失常的发生,改善慢性期心室电不稳定性。     

The impact of right ventricular infarction on the prevalence of ventricular arrhythmias during acute inferior myocardial infarction

To determine the impact of RV infarction on the prevalence and complexity of ventricular arrhythmias during inferior AMI, 57 patients with no prior MI were studied by 24-hour Holter monitoring on the first and tenth days of AMI. Based on radionuclear studies, patients were allocated into two groups: (1) group A, 21 patients (37 percent) with normal RVEF (greater than or equal to 40 percent); and (2) group B, 36 patients (63 percent) with depressed RVEF (less than 40 percent). There were no significant differences between the groups regarding age and LVEF. Values of RVEF were 47 +/- 6 percent and 31 +/- 6 percent, respectively (p less than 0.05). The RVEF had no influence on the prevalence and complexity of early and late arrhythmias. Stratification of patients in group B into two subgroups based on the extent of RV dysfunction did not reveal any differences in the occurrence of all forms of ectopy (when both groups were matched to group A). Therefore, patients with inferior AMI, with or without RV infarction, have a similar prevalence of arrhythmias. Ventricular ectopic beats may be related to the severity and spread of LV involvement, rather than to RV dysfunction.