Use of electrogram characteristics during sinus rhythm to delineate the endocardial scar in a porcine model of healed myocardial infarction

INTRODUCTION: Substrate-based catheter ablation of postmyocardial infarction (post-MI) ventricular tachycardia necessitates electroanatomic definition of the scarred endocardium. We sought to determine whether electrogram criteria during sinus rhythm could identify the location and extent of the myocardial scar by electroanatomic mapping. METHODS AND RESULTS: A porcine model of healed MI was generated by injecting agarose microspheres into the mid left anterior descending coronary artery. At least 4 weeks post-MI, the animals (n = 24) underwent detailed left ventricular endocardial electroanatomic mapping using a 4-mm-tip catheter (BioSense-Webster, Inc.). Based upon mapping data in normal animals, infarcted tissue was defined as bipolar electrogram amplitude < 1.5 mV and electrogram duration > or = 50 msec. Radiofrequency ablation lesions (2-10 per animal) were placed to tag the endocardial borders of the electroanatomic mapping-defined scar. The area of the scar defined by abnormal voltage amplitude was 25.9 +/- 15.4 cm2 (range 6.9-60.5). This area correlated well with that defined as scar by the electrogram duration criteria (26.4 +/- 16 cm2). Of those points remote from the infarct with falsely low voltage amplitude resulting from presumed poor catheter-tissue contact, 94% were correctly identified as normal when using the electrogram duration criteria. Late potentials were observed predominantly along the borders of the infarcted myocardium. The radiofrequency lesions placed to tag the scar borders were located along the scar periphery during gross pathologic examination. CONCLUSION: During normal sinus rhythm, both bipolar electrogram voltage amplitude and electrogram duration criteria are able to help differentiate normal from scarred myocardial tissue. Using these criteria, a detailed reconstruction of the endocardial scar can be rendered by electroanatomic mapping of the heart.     

Electrophysiological effects of acute ischaemia on electrically stable myocardial infarction

The purpose of this study was to examine the effects of acute ischaemia superimposed on an electrophysiologically stable, small myocardial infarction, and to determine the mechanisms of induced ventricular arrhythmias, using a canine infarction model. Ten dogs without inducible ventricular tachycardia or fibrillation on the 7th day post-myocardial infarction (Group 1) and 14 control dogs (Group 2) were subjected to 30 min acute ischaemia by occlusion of the proximal left anterior descending artery. The areas of infarcted myocardium ranged from 1.0 to 20.4% (mean 8.9, SD 7.7) of total left ventricular weight. Ventricular arrhythmias were inducible by programmed electrical stimulation in eight of 10 dogs (80%) after acute ischaemia, but in only one of 14 control dogs (7%) (p less than 0.005). In seven of eight Group 1 dogs, epicardial mapping showed that ventricular arrhythmias did not originate from the epicardial region. In one dog, in which there was simultaneous epicardial and endocardial mapping, an endocardial electrogram from the boundary area between infarcted and acutely ischaemic zones recorded continuous fragmented activity. It was thus suggested that re-entry in a relatively isolated endocardial site could be attributed to the induction of ventricular tachyarrhythmias, and that the electrical instability could be significantly enhanced during acute ischaemia when underlying myocardial infarction was present.     

Tritiated digoxin. XX. Tissue distribution in experimental myocardial infarction

The role and potential hazards of digitalis glycoside administration in acute myocardial infarction remain controversial. We investigated the concentration of tritiated digoxin in normal, ischemic, and infarcted left ventricular myocardium of the dog after ligation of the anterior interventricular coronary artery. The normal homogeneous distribution of tritiated digoxin in the normal canine left ventricle was altered following acute myocardial infarction. The ischemic and infarcted zones exhibited a marked diminution in digoxin concentration. Oxidative phosphorylation determinations confirmed tissue hypoxia in the infarcted zone. The gradient of digoxin concentration between normal, ischemic, and infarcted zones of myocardium may potentiate the development of an arrhythmia in the electrically unstable infarcted myocardium.     

Cellular electrophysiological changes during ischemia in isolated, coronary-perfused cat ventricle with healed myocardial infarction

Cellular electrophysiological consequences of acute ischemia superimposed on healed myocardial infarction were studied in isolated, coronary-perfused cat left ventricles 2-4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, and the preparations were superfused with Tyrode's solution gassed with 95% N2-5% CO2. Transmembrane action potentials were recorded from the endocardial cells in normal and infarcted zones. There were no significant differences in measured action potential variables and refractory periods between cells in the normal and infarcted zones before acute ischemia. When coronary perfusion was discontinued ("ischemia"), resting potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened progressively in cells of the normal zone. However, the action potential changes were less prominent, and the refractory period was unchanged in cells in the infarcted zone. As a result, there were significant differences in resting membrane potential, action potential amplitude, action potential duration, and refractory period between cells in the normal and infarcted zones at 10 minutes of ischemia. These differences became larger as the ischemic period was prolonged. Spontaneous rapid ventricular activity was observed during the last 20-30 minutes of ischemia in four of eight preparations with healed myocardial infarction, whereas no spontaneous rapid ventricular activity was recorded in any of six normal heart preparations. Our data suggest that superimposition of acute ischemia on healed myocardial infarction produces electrophysiological inhomogeneities that may enhance arrhythmogenesis.     

Basic fibroblast growth factor increases regional myocardial blood flow and salvages myocardium in the infarct border zone in a rabbit model of acute myocardial infarction.

Basic fibroblast growth factor (bFGF) has been shown by some to promote angiogenesis and myocardial salvage in experimentally induced acute myocardial infarction. Although these findings have spurred much clinical interest, they are not universally observed, and the true efficacy of bFGF remains unclear. The authors used a rabbit model of acute myocardial infarction to further elucidate the effects of bFGF on acutely infarcted myocardium containing few collaterals. Myocardial infarction was evoked by ligation of the left coronary artery. Prior to ligation, either 100 microg of bFGF (bFGF group; n = 15) or physiological saline (control group; n = 22) was injected into the myocardium supplied by the ligated artery. With use of nonradioactive colored microspheres, regional blood flow (Qm) was measured before, immediately after, and 4 weeks after coronary artery ligation. Infarct and border zone sizes were measured in cross-sectional slices of the resected hearts, and the amount of viable myocardium (myocardium score) and the extent of fibrosis were histologically determined in each area. Four weeks after ligation, Qm values in the infarcted area did not significantly differ between the bFGF and control groups (0.54 +/- 0.36 vs 0.48 +/- 0.30 mL/min/g); in the border zone, Qm tended to be higher in the bFGF group (3.39 +/- 2.68 vs 1.47 +/- 0.80 mL/min/g), but the difference was not significant; finally in the noninfarcted area, Qm was significantly (p < 0.05) higher in the bFGF group (6.06 +/- 3.85 vs 2.09 +/- 0.82 mL/min/g). There was no significant difference in the amount of viable myocardium or the extent of fibrosis in the infarcted areas of the two groups. In the border zone, however, the amount of viable myocardium was significantly (p < 0.005) larger in the bFGF group (61.8 +/- 8.5% vs 35.8 +/- 20.3% of the visual field). Likewise, as graded on a scale from 0 to 5, the extent of fibrosis was significantly (p < 0.005) less in the bFGF group (2.1 +/- 0.5 vs 3.3 +/- 0.8). In conclusion, injection of bFGF into acutely infarcted myocardium increased blood flow to the noninfarcted area and salvaged the myocardium in the border zone.     

Detailed endocardial mapping accurately predicts the transmural extent of myocardial infarction

OBJECTIVES: This study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping. BACKGROUND: The degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue. METHODS: Electromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data. RESULTS: From the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 +/- 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7 mV, 0.8 +/- 0.4 mV in the three groups respectively, p < 0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (<30%) and second transmurality subgroups. CONCLUSIONS: The degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.     

Electrophysiologic sequelae of chronic myocardial infarction: local refractoriness and electrographic characteristics of the left ventricle

Ventricular tachycardia (VT) has been shown to arise from ischemically damaged left ventricular myocardium, which possesses heterogeneity of refractoriness and activation. Catheter techniques were used to study left ventricular refractoriness using the strength-interval relation and activation by local electrographic characteristics in 8 patients with and 6 patients without previous myocardial infarction (MI). Noninfarcted myocardium in patients with and without previous MI was similar overall with respect to refractoriness and excitability, whereas local electrographic duration in MI patients was longer (66 +/- 2 vs 52 +/- 3 ms, p less than 0.005) and amplitude lower (3.9 +/- 2.1 vs 6.1 +/- 2.0 mV, p less than 0.05). Comparisons of infarcted and noninfarcted regions in MI patients revealed an increased threshold of excitability at infarct sites (e.g., 1.9 +/- 1.0 vs 0.7 +/- 0.4 mA, p less than 0.05) and prolongation of refractory periods (375 +/- 118 vs 275 +/- 13 ms, p less than 0.05) at the lowest level of stimulating current. Shortening of refractory period as a result of change in pacing cycle length was not affected by infarction. The local electrographic duration (95 +/- 17 ms) was significantly longer in infarcted regions than at noninfarcted sites (p less than 0.005), but the electrographic amplitude (3.4 +/- 3.0 mV) differed significantly only in noninfarct patients. It is concluded that considerable electrophysiologic disparity exists between infarcted and noninfarcted myocardium. Whether or not arrhythmogenic tissue possesses unique alterations in electrophysiologic characteristics remains to be established.     

Gene expression and in situ localization of diacylglycerol kinase isozymes in normal and infarcted rat hearts: effects of captopril treatment

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.     

Tissue-specific variability in human epicardial impedance

Epicardial Impedance Mapping . Introduction: Epicardial ablation can be employed to treat ventricular tachycardia. Voltage attenuation in regions of fat can mimic epicardial scar, limiting its specificity. Ablation over fat may not be as effective. Prior animal data have shown that infarcted myocardium has lower impedance than normal, and human bioimpedance studies suggest peripheral fat displays higher impedance. Therefore, we tested the hypothesis that human epicardial fat has higher impedance than myocardium when measured with standard ablation tools. Methods: Patients undergoing elective surgery for coronary artery or valve disease were enrolled. A reference patch was placed on the patients’ back between the scapulae and connected to a standard RF generator (Stockert, GmBH, Germany). Impedance was measured by passing a 1 μA, 50 kHz current from the catheter tip to the patch. After sternotomy but before initiation of cardiopulmonary bypass, an ablation catheter (Celsius, Biosense Webster, Diamond Bar, CA, USA) was placed onto the epicardial surface in ventricular regions visually identified as fat or myocardium. At each site, impedance was recorded from the generator. Results: A total of 37 (7 patients) points were sampled. Impedance was significantly higher in regions of fat versus normal muscle (697 Ω vs. 301 Ω; P = 0.01). Moreover, normal sites from the LV had higher impedance than from the RV (381 Ω vs. 271 Ω; P = 0.01). Conclusions: Human epicardial fat has higher tissue impedance than normal muscle. Using epicardial impedance and voltage mapping in conjunction may improve differentiation of arrhythmia substrate from epicardial fat and improve the efficacy of epicardial ablation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 436‐439)     

Inducible sustained ventricular tachycardia 4 years after experimental canine myocardial infarction: electrophysiologic and anatomic comparisons with early healed infarcts

We studied a group of 17 dogs 4 to 6 years after infarction produced by 2 hr occlusion of the anterior descending coronary artery followed by reperfusion. Dogs in this "late" infarct group were compared with a group of 24 dogs with "early" healed infarcts (2 to 24 weeks old). With signal-averaging techniques body surface potentials were recorded during sinus rhythm. After thoracotomy epicardial electrograms were recorded from 45 standardized sites within the infarcted region and characteristics of selected electrograms were compared with anatomic features of underlying myocardium. Epicardial recordings from the late infarct group demonstrated earlier local activation (p less than .001) and shorter electrogram duration (p less than .001) when compared with recordings from the early infarct group. There was less temporal dispersion of activation and electrogram duration among the 45 sites in dogs with late infarcts as measured by respective coefficients of variance (p = .007 and less than .001). With programmed stimulation six dogs in the late and eight in the early infarct group exhibited inducible sustained ventricular tachycardia. Mean cycle length of the tachycardia in dogs with late infarcts was significantly shorter (p = .035). Late potentials were notably less prominent in dogs in the late infarct group with ventricular tachycardia than in dogs in the early infarct group. Fewer abnormal electrophysiologic characteristics of late infarcts coincided with relatively less scar in the underlying myocardium. Moreover, the strength of electrophysiologic-anatomic correlations differed in late as opposed to early infarcts. The latter findings suggest long-term evolution of infarct anatomy. We conclude that a substrate for reentrant tachycardia is present in dogs 4 to 6 years after reperfused infarction. Conduction characteristics are less abnormal in these late healed infarcts and are associated with a shorter ventricular tachycardia cycle length and less pronounced late potentials on the body surface.     

Effects of lidocaine and procainamide on normal and abnormal intraventricular electrograms during sinus rhythm

The effect of lidocaine (n = 6) and procainamide (n = 12) on electrogram characteristics from electrically normal right ventricular and electrically abnormal left ventricular endocardial sites was determined in 18 patients with prior myocardial infarction. Bipolar electrograms were recorded during sinus rhythm with No. 6F catheters positioned at a left ventricular abnormal site (electrograms fulfilling two of the following criteria: amplitude less than 3 mV, duration greater than 70 msec, or an amplitude to duration ratio less than .046) and normal sites at the right ventricular apex (RVA) and right ventricular outflow tract (RVOT). All electrograms were recorded from the same location before and after intravenous lidocaine or procainamide administered to obtain mean serum concentrations of 4.2 +/- 0.6 and 9.42 +/- 2 micrograms/ml respectively. Lidocaine and procainamide had no significant effect on sinus cycle length or electrogram amplitude. After lidocaine, no significant change in QRS width (112 +/- 23 vs 114 +/- 24 msec), left ventricular electrogram duration (76 +/- 21 vs 78 +/- 15 msec), or right ventricular electrogram duration (RVA 33 +/- 9 vs 33 +/- 10 msec, RVOT 31 +/- 9 vs 33 +/- 11 msec) was noted during sinus rhythm. At a paced cycle length of 600 msec, there was also no change in the paced QRS duration (197 vs 198 msec), the RVA electrogram duration (30 vs 32 msec), the RVOT electrogram duration (49 vs 52 msec), or the left ventricular electrogram duration (102 vs 108 msec).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vector mapping of myocardial activation

A custom-made probe, consisting of four electrodes arranged so that two orthogonal bipolar electrograms could be recorded from a single site, was used to record epicardial activity during atrial and ventricular pacing in five normal and five anesthetized open-chest mongrel dogs with myocardial infarction. Unfiltered bipolar electrograms recorded with a 2 mm interelectrode distance averaged 36 +/- 15 mV in amplitude and 16 +/- 5 msec in duration in normal areas and 14 +/- 11 mV and 23 +/- 12 msec in infarcted areas (p less than .01 infarct vs normal). The bipolar electrograms were vector summed so that a vector loop could be generated at each site. The direction of epicardial impulse propagation as determined by multipoint isochronal activation mapping was compared with that indicated by maximum x,y deflection of the vector loop. At 203 sites (141 normal and 62 infarcted) there was a median error of only 13 degrees and an excellent correlation by linear regression (r2 = .95). In normal myocardium vector loops were straight (60%), open (21%), or hooked (19%). In infarcted myocardium, notched and irregular loops were occasionally seen. However, a clear maximum x,y deflection was still obtained from 98% of infarcted sites. During ventricular pacing in normal dogs, uniform epicardial conduction was observed for up to 4 cm longitudinal to fiber orientation but only 1 cm transverse to it. At selected sites longitudinal to fiber orientation conduction velocity was 0.618 m/sec, electrogram duration 12 msec, and vector amplitude 76 mV compared with 0.304 m/sec, 18 msec, and 38 mV during conduction transverse to fiber orientation (p less than .05 for all comparisons). Vector mapping of epicardial activation was performed during ventricular tachycardia induced by programmed stimulation in two of five 2-week-old canine myocardial infarcts. Aside from minor irregularities caused by impulse spread around areas of block, vector loops indicated when impulses were spreading away from the area of early epicardial activity and thus directed mapping to the region of earliest activation. We conclude that vector loops generated by summing orthogonal local bipolar electrograms accurately represent the direction of epicardial activation in both normal and infarcted myocardium. Such loops may prove useful in mapping tachycardias and in clarifying details about cardiac activation processes.     

Relationship of specific electrogram characteristics during sinus rhythm and ventricular pacing determined by adaptive template matching to the location of functional reentrant circuits that cause ventricular tachycardia in the infarcted canine heart

INTRODUCTION: It would be advantageous, for ablation therapy, to localize reentrant circuits causing ventricular tachycardia by quantifying electrograms obtained during sinus rhythm (SR) or ventricular pacing (VP). In this study, adaptive template matching (ATM) was used to localize reentrant circuits by measuring dynamic electrogram shape using SR and VP data. METHODS AND RESULTS: Four days after coronary occlusion, reentrant ventricular tachycardia was induced in the epicardial border zone of canine hearts by programmed electrical stimulation. Activation maps of circuits were constructed using electrograms recorded from a multichannel array to ascertain block line location. Electrogram recordings obtained during SR/VP then were used for ATM analysis. A template electrogram was matched with electrograms on subsequent cycles by weighting amplitude, vertical shift, duration, and phase lag for optimal overlap. Sites of largest cycle-to-cycle variance in the optimal ATM weights were found to be adjacent to block lines bounding the central isthmus during reentry (mean 61.1% during SR; 63.9% during VP). The distance between the mean center of mass of the ten highest ATM variance peaks and the narrowest isthmus width was determined. For all VP data, the center of mass resided in the isthmus region occurring during reentry. CONCLUSION: ATM high variance measured from SR/VP data localizes functional block lines forming during reentry. The center of mass of the high variance peaks localizes the narrowest width of the isthmus. Therefore, ATM methodology may guide ablation catheter position without resorting to reentry induction.     

Effect of cellular uncoupling by heptanol on conduction in infarcted myocardium

Experiments were performed in vitro on six normal thin ventricular epicardial tissue strips and 10 strips removed from the infarcted regions of dogs 21-60 days after experimental myocardial infarction. Conduction was evaluated by mapping activation sequences at 40-45 sites over an area of 1 x 2 cm during pacing at a basic cycle length of 2,000 msec. The amplitude and length of recorded electrograms were also determined at each site. After control recordings, heptanol, which increases gap junctional resistance, was added to the tissue bath at concentrations ranging between 0.2 and 1.0 mM. In contrast to its effect on normal tissues, heptanol caused 75 of 260 previously active sites in the infarcted tissues to become inactive. The affected sites were located in areas of very slow conduction and/or adjacent to areas of preexisting conduction block. In addition, heptanol decreased the length and degree of fractionation of electrograms recorded in slowly conducting regions of the infarcted tissues. The magnitude of the decrease in electrogram length following heptanol was related to the degree of electrogram abnormality during control as reflected in the ratio of electrogram length to amplitude. Heptanol shortened electrograms by causing local conduction block, which eliminated some components of the fractionated electrograms. In an additional eight epicardial strips removed from the infarcted region, 0.5 mM heptanol had only a slight effect (10.7% decrease) on the maximum rate of membrane depolarization. Thus, heptanol does not act primarily by way of depressing the fast inward current. We conclude from heptanol's effects on conduction and electrogram characteristics that slow and dissociated conduction in the infarcted region is due to an abnormality in gap junctional distribution between surviving cells and/or an abnormality in individual gap junctional function.     

Essential role of ICAM-1/CD18 in mediating EPC recruitment, angiogenesis, and repair to the infarcted myocardium

Bone marrow-derived endothelial progenitor cells (EPCs) have the ability to migrate to ischemic organs. However, the signals that mediate trafficking and recruitment of these cells are not well understood. Using a functional genomics strategy, we determined the genes that were upregulated in the ischemic myocardium and might be involved in EPC recruitment. Among them, CD18 and its ligand ICAM-1 are particularly intriguing because CD18 and its heterodimer binding chains CD11a and CD11b were correspondingly expressed in ex vivo-expanded EPCs isolated from rat and murine bone marrows. To further verify the functional role of CD18 in mediating EPC recruitment and repair to the infarcted myocardium, we used neutralizing antibody to block CD18. Blockade of CD18 in EPCs significantly inhibited their attachment capacity in vitro and reduced their recruitment to the ischemic myocardium in vivo by 95%. Moreover, mice receiving EPCs that were treated with control isotype IgG exhibited significantly increased capillary density in the infarct border zone, reduced cardiac dilatation, ventricular wall thinning, and fibrosis when compared with myocardial infarction mice receiving PBS and CD18 blockade reversed the EPC-mediated improvements to the infarcted heart. Thus, our results suggest an essential role of CD18 in mediating EPC recruitment and the subsequent functional effects on the infarcted heart.     

抗心肌肌凝蛋白抗体亲大鼠梗塞心肌特性的研究

目的　探讨抗心肌肌凝蛋白单克隆抗体 (antimyosinantibody ,AMA)亲梗塞心肌的特点。方法　心肌梗死大鼠静脉注射放射性锝 99m标记的抗心肌肌凝蛋白单克隆抗体 (99mTc AMA) ,观察注射时间 ,梗死时间和梗塞区对梗塞心肌摄取AMA的影响。结果　注射后 2h梗塞心肌开始摄取AMA ,以后摄取逐渐增加 ,2 4h达到高峰。心肌梗死后 2 0d ,梗塞心肌持续摄取AMA ,期间心肌梗死后 1～ 5d摄取最强 ,梗塞中央区以及梗塞区内层摄取强于其他梗塞区域。结论　急性心肌梗死大鼠梗塞心肌特异性地摄取AMA ,注射AMA后摄取迅速、持久 ,受心肌梗死时间影响较小 ,梗塞中央区内层心肌摄取最强 ,AMA具有亲梗塞心肌的特性。     

大麻素Ⅱ型受体激动剂促进小鼠心肌梗死后心脏干／祖细胞增殖的作用

目的：探讨大麻素Ⅱ型受体（CB2）选择性激动剂AMl241对小鼠心肌梗死（MI）模型中心脏干／祖细胞增殖的作用。方法：40只雄性C57BL／6小鼠通过结扎小鼠心脏左冠状动脉前降支建立MI模型并随机分为4组,每组10只（n=10）：①假手术（Sham）组;②MI组;③MI＋CB：受体激动剂AMl241（MI＋AMl241）组;④MI＋CB2受体激动剂AMl241＋CB2受体拮抗剂AM630（MI＋AMl241＋AM630）组。采用小动物超声系统观察小鼠左室射血分数（LVEF）的变化。用免疫荧光染色法观察MI周边区表达干细胞生长因子受体（c-kit）、干细胞抗原1（Sea-1）的阳性细胞数,实时荧光定量PCR测定MI周边区c-kit、Sea-1和多药耐药蛋白P糖蛋白（MDRl）的表达水平。结果：与MI组相比,MI＋AMl241组小鼠7d和14d心脏LVEF值显著提高（P〈0．01）。免疫荧光染色的结果提示,MI＋AMl241组c-kit和Sea-1的表达较MI组增多（P〈0．05）。实时荧光定量PCR结果显示,MI＋AMl241组c-kit和Sea-1的基因表达水平明显高于MI组（P〈0．05）。同时,CB2受体拮抗剂AM630可阻断AMl241的上述作用。结论：CB2受体激活可促进梗死心肌干／祖细胞的增殖,改善心脏的收缩功能。     

Heterogeneous changes in K currents in rat ventricles three days after myocardial infarction

OBJECTIVE: After coronary artery occlusion, surviving myocardium in and around the infarct zone plays an important role in arrhythmogenesis. Understanding the mechanisms for derangements in cardiac electrical activity at the cellular and molecular levels is important for the design of effective therapeutic strategies. METHODS: To provide part of that understanding, we studied changes in K channel function and expression in rat ventricular myocardium three days after occluding the left major coronary artery. The epicardium and endocardium of infarcted region in the left ventricle and the free wall of right ventricle were separated for myocyte isolation, followed by whole-cell voltage clamp studies. Myocytes were also isolated from corresponding regions of control and sham-operated hearts and studied under the same conditions. RESULTS: We found that the transient outward (Ito), delayed rectifier (IK) and inward rectifier (IKI) currents have different distribution patterns in normal rat ventricular myocardium. Sham-operation did not affect any of these K currents in left ventricular myocytes, but coronary artery occlusion caused a reduction of all three. For Ito and IKI the reduction was greater in epicardial than in endocardial myocytes, but IK was reduced equally in these two cell groups. Unexpectedly, Ito and IK as well as cell capacitance were increased in right ventricular myocytes from infarcted as well as sham-operated hearts. Western blot analysis indicated that the level of Kv4 channel proteins (Kv4.2 + Kv4.3) was reduced in infarcted left ventricular myocardium, consistent with the reduction in Ito. CONCLUSION: Our data suggest that the distribution of K channels and changes in them induced by coronary artery occlusion are heterogeneous in ventricular myocardium. Understanding the molecular mechanisms for this heterogeneity and its implications in arrhythmogenesis poses a challenge in designing effective antiarrhythmic therapy for myocardial infarction patients.     

Prognostic significance of ventricular late potentials in the postmyocardial infarction period

Ventricular late potentials in patients after myocardial infarction can be assumed to herald an increased risk of future sudden cardiac death or symptomatic sustained ventricular tachycardia. This holds particularly true for patients studied early after recent myocardial infarction whereas patients assessed later in the subsequent course have a substantially lesser incidence of arrhythmic events, probably due to intercurrent death of those at high risk. Of prognostic importance appears not only the presence but also the duration of late potentials. A meaningful role is also assumed by the extent of left ventricular functional impairment (EF less than 40%). However, in consideration of the complex mechanisms that can lead to sudden cardiac death, no single method predicts with high sensitivity the occurrence of a ventricular tachyarrhythmic event. Sudden cardiac death can be incurred on the basis of chronic electrophysiological abnormalities as a consequence of regional slow conduction in the border zone of a previous myocardial infarction precipitated by trigger factors such as spontaneous ventricular arrhythmias. Sudden cardiac death or symptomatic sustained ventricular tachycardia can also occur due to sudden and transient changes in the electrophysiological properties of the myocardium due to ischemia. Whether the combination of late potentials with clinical parameters such as ventricular arrhythmias detected in the ambulatory ECG and those induced with programmed electrical stimulation will lead to more accurate identification of patients at risk prerequisites further elucidation. Currently available literature indicates that in patients with late potentials, ventricular tachycardias can be induced more frequently by programmed electrical stimulation and that the combination of both phenomena confers a particularly high risk.     

Dual‐Dye Optical Mapping after Myocardial Infarction: Does the Site of Ventricular Stimulation Alter the Properties of Electrical Propagation?

Introduction: Myocardial infarction (MI) disrupts electrical conduction in affected ventricular areas. We investigated the effect of MI on the regional voltage and calcium (Ca) signals and their propagation properties, with special attention to the effect of the site of ventricular pacing on these properties.
Methods: New Zealand White rabbits were divided into four study groups: sham-operated (C, n = 6), MI with no pacing (MI, n = 7), MI with right ventricular pacing (MI + RV, n = 6), and MI with BIV pacing (MI + BIV, n = 7). At 4 weeks, hearts were excised, perfused, and optically mapped. As previously shown, systolic and diastolic dilation of the LV were prevented by BIV pacing, as was the reduction in LV fractional shortening.
Results: Four weeks after MI, optical mapping revealed markedly reduced action potential amplitudes and conduction velocities (CV) in MI zones, and these increased gradually in the border zone and normal myocardial areas. Also, Ca transients were absent in the infarcted areas and increased gradually 3–5 mm from the border of the normal zone. Neither BIV nor RV pacing affected these findings in any of the MI, border, or normal zones.
Conclusions: MI has profound effects on the regional electrical and Ca signals and on their propagation properties in this rabbit model. The absence of differences in these parameters by study group suggests that altering the properties of myocardial electrical conduction and Ca signaling are unlikely mechanisms by which BIV pacing confers its benefits. Further studies into the regional, cellular, and molecular benefits of BIV pacing are therefore warranted.