小鼠急性心肌梗死后心脏破裂的性别差异及机制探讨

目的:探讨小鼠急性心肌梗死(AMI)后心脏破裂的性别差异及其机制。方法:不同性别C57BL小鼠,随机分入假手术组、心肌梗死组。建立AMI模型后,观察不同性别组心脏破裂发生率,并于AMI后第7天行超声和血流动力学检查;应用酶谱法、病理染色及免疫组化方法,分别于AMI后第3天、第7天检测基质金属蛋白酶(MMP-2,MMP-9)活性表达,心肌间质胶原含量(CVF)和类型的变化,检测AMI后第3天炎性细胞浸润程度。结果:1.AMI后雄性组心脏破裂率显著高于雌性组(42.2%与18.4%,P<0.05)。2.与雌性组比较,雄性心肌梗死(MI)组AMI后第3天炎性细胞浸润程度明显增加(P<0.05),第3天、第7天MMP-9表达增加,心肌间质胶原含量较低。3.雄性假手术组平均动脉压(MAP)、左心室收缩压(LVSP)均高于雌性假手术组(P均<0.05),术后第7天时,雄性MI组较雌性MI组表现出显著的左心室扩张、梗死区变薄、心功能障碍以及血流动力学恶化。结论:小鼠AMI后心脏破裂率存在性别差异,雄性明显高于雌性。炎性细胞浸润程度增加、MMP-9活性增高、原有间质胶原过度降解和左心室早期重塑恶化可能是雄性小鼠心脏破裂率增加的重要原因。     

Relationship between mitral regurgitation and myocardial viability after acute myocardial infarction: their impact on prognosis

Mitral regurgitation (MR) after acute myocardial infarction (AMI) is an important prognostic factor. Although its mechanisms are still debated, ventricular remodeling probably plays an important role. Because myocardial viability (MV) in the infarct zone reduces infarct expansion and ventricular remodeling, it is also possible that its presence counteracts the development of mitral regurgitation in infarcted patients. To evaluate this issue 191 patients with uncomplicated AMI, wall motion abnormalities (akinesis) and semiquantitative evaluation of MR were retrospectively selected from those consecutively examined at our echo-laboratory to evaluate MV using low-dose dobutamine echocardiography (DbE). Follow-up evaluation was performed at 30+/-13 months. Seventy-nine patients had no MR; 86 patients had grade 1 MR, 11 patients had grade 2 MR, nine patients had grade 3 MR, and six patients had grade 4 MR. Patients with significant MR (>grade 1) were older (63+/-7 vs. 59+/-10 years, P=0.03), had lower reduction of RWMSI (DeltaRWMSI) during DbE (0.08+/-0.11 vs. 0.22+/-0.28, P=0.01), more stenotic vessels at coronary angiography (2.35+/-0.93 vs. 1.67+/-1.12, P=0.01), and more frequently had anterior-inferior AMI (P<0.0001); they also had a non-significant tendency to higher RWMSI (2.04+/-0.38 vs. 1.92+/-0.28, P=0.06). In a multivariate regression analysis, DeltaRWMSI proved to be significantly related to the grade of MR (P=0.02). Eighteen patients died during follow-up. Death was more frequent in patients with MR (10/165 vs. 8/26, P=0.0003). At multivariate stepwise Cox regression analysis both the extent of ventricular dysfunction and the presence of MR were significantly related to mortality (P<0.0001 and P=0.01, respectively); DeltaRWMSI showed a non-significant tendency to influence mortality (P=0.09). When MR was excluded from the multivariate analysis, DeltaRWMSI remained significantly related to mortality (P=0.05). In conclusion our study suggests that the presence of MV in infarcted patients influences the development of MR. This reduction of MR may be one of the mechanisms by which MV affects mortality after AMI and should be considered in all studies that evaluate MV after myocardial infarction.     

Biomechanical properties of reperfused transmural myocardial infarcts in rabbits during the first week after infarction. Implications for left ventricular rupture.

Left ventricular (LV) rupture potential was studied after transmural myocardial infarction (MI) in rabbits by measuring 1) the tensile strength of infarcted tissue strips, 2) the force required to initiate a tear (tear threshold) in the central infarcted region, and 3) the intracavitary pressure required to rupture the infarcted ventricle. During the first week after MI, infarcts resulting from a permanent coronary occlusion were compared with infarcts reperfused "late" (i.e., 3 hours) after coronary occlusion with a resultant hemorrhagic transmural infarct but no reduction in infarct size. The reperfused hemorrhagic infarcted strips had less tensile strength than strips from permanently occluded infarcts in the initial 24 hours after MI (16 +/- 1 versus 24 +/- 3 g/mm2, p less than 0.05), but the tear threshold and response to increased LV pressure were not influenced by infarct reperfusion at this time. By 3 days after MI, reperfused infarcts had equal tensile strength, had greater resistance to infarct tearing, and could withstand a greater LV distending pressure compared with permanently occluded infarcts. By 5 days after MI, reperfused infarcts maintained a greater tear threshold but had less tensile strength than permanently occluded infarcts, although all infarct values were equivalent or greater than normal LV values. By 7 days after MI, reperfused and permanently occluded infarcts were equally strong by all measurements. Thus, late reperfusion of transmural infarcts increased resistance to infarct tearing and LV rupture above that of nonreperfused permanently occluded infarcts by 3 days after MI and enhanced tissue strength after an initial 24-hour vulnerable period. These findings suggest that late reperfusion may accelerate myocardial healing after MI.     

Frequency of rupture of the left ventricular free wall or ventricular septum among necropsy cases of fatal acute myocardial infarction since introduction of coronary care units

Review of 18 published reports before the widespread use of cardiac care units disclosed that the frequency of rupture of the left ventricular free wall or ventricular septum among necropsy cases of acute myocardial infarction (AMI) ranged from 4 to 24% (mean 8%) (619 of 7,905 cases). The frequency of rupture of the left ventricular free wall or ventricular septum among necropsy patients with fatal AMI studied in this laboratory since 1968 was analyzed. Of 648 such patients, 204 (31%) had rupture of the left ventricular free wall or ventricular septum. Rupture occurred in 171 (40%) of 431 patients without healed myocardial infarcts (grossly visible left ventricular scars), and in 29 (13%) of 217 patients with a healed myocardial infarct (p less than 0.01). Thus, the frequency of rupture of the left ventricular free wall or ventricular septum during AMI appears to have increased substantially since the widespread use of coronary care units. Also, the frequency of rupture is nearly 3 times greater in those in whom rupture occurred during the first AMI compared to those with a previous infarct that healed.     

Differences in inflammation, MMP activation and collagen damage account for gender difference in murine cardiac rupture following myocardial infarction

Cardiac rupture remains a fatal complication of acute myocardial infarction (MI) with its mechanism partially understood. We hypothesized that damage to the collagen matrix of infarcted myocardium is the central mechanism of rupture and therefore responsible for the difference in the incidence of rupture between genders. We examined left ventricular (LV) remodeling during the acute phase post-MI in 129sv mice. Following induction of MI, we monitored rupture events and assessed the extent of LV remodeling by echocardiography. Muscle tensile strength, content of insoluble and soluble collagen, expression and activity of matrix metalloproteinases (MMPs) and density of inflammatory cells were determined in the infarcted and non-infarcted myocardium. We then tested the effects of MMP inhibition on rupture. Compared to female mice, males with MI displayed greater extent of LV remodeling, reduced muscle tensile strength, loss of insoluble collagen, local inflammatory response and MMP-9 activation, changes associated with a 3 times higher incidence of rupture than in females. MMP-9 expression by circulating blood mononuclear cells was also increased in male mice with acute MI. Treatment of male mice with an MMP inhibitor reduced MMP activity and halved rupture incidence. Our findings demonstrate that the differences in the severity of inflammation, MMP activation and damage to collagen matrix account for gender difference in cardiac rupture. Our study illustrates the breakdown of fibril collagen as a central mechanism of cardiac rupture.     

Patency of the infarct-related coronary artery and ventricular geometry.

The pathogenesis of acute myocardial infarction (AMI) involves a sudden thrombotic occlusion of a coronary artery. Spontaneous or pharmacologic thrombolysis may lead to myocardial salvage if patency is achieved within a narrow time window. However, patients in whom thrombolysis occurs late seem to demonstrate improved left ventricular (LV) function and prognosis, which may be independent of myocardial salvage. Preservation of normal LV geometry by reducing expansion of the infarcted segment is a likely mechanism for this benefit. Infarct expansion is most pronounced in patients with anterior wall AMI who have a persistently occluded infarct-related vessel. This process of expansion leads to early increases in LV volume and distortions of LV contour (abnormal LV geometry). Patients whose infarct segment is largest, patients who have manifested infarct expansion, and patients with a persistently occluded infarct-related artery are at highest risk for progressive LV dilation. Experimental data support the concept that reperfusion of occluded vessels that occurs too late for myocardial salvage will preserve LV geometry by limiting infarct expansion. Prospective clinical trials should address whether there is a late, "second time window" during which infarct expansion and distortions of LV geometry may be reduced by (1) therapy with thrombolytic agents applied late after infarction, (2) late mechanical reperfusion with percutaneous transluminal coronary angioplasty (PTCA) or related methods, and (3) load-reducing agents to decrease remodeling, such as angiotensin-converting enzyme inhibitors or nitroglycerin.     

Acute Myocardial Infarction with Hyperoxemic Therapy (AMIHOT): a prospective, randomized trial of intracoronary hyperoxemic reperfusion after percutaneous coronary intervention.

OBJECTIVES: This study sought to determine whether hyperoxemic reperfusion with aqueous oxygen (AO) improves recovery of ventricular function after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Hyperbaric oxygen reduces myocardial injury and improves ventricular function when administered during ischemia-reperfusion. METHODS: In a prospective, multicenter study, 269 patients with acute anterior or large inferior AMI undergoing primary or rescue PCI (<24 h from symptom onset) were randomly assigned after successful PCI to receive hyperoxemic reperfusion (treatment group) or normoxemic blood autoreperfusion (control group). Hyperoxemic reperfusion was performed for 90 min using intracoronary AO. The primary end points were final infarct size at 14 days, ST-segment resolution, and delta regional wall motion score index of the infarct zone at 3 months. RESULTS: At 30 days, the incidence of major adverse cardiac events was similar between the control and AO groups (5.2% vs. 6.7%, p = 0.62). There was no significant difference in the incidence of the primary end points between the study groups. In post-hoc analysis, anterior AMI patients reperfused <6 h who were treated with AO had a greater improvement in regional wall motion (delta wall motion score index = 0.54 in control group vs. 0.75 in AO group, p = 0.03), smaller infarct size (23% of left ventricle in control group vs. 9% of left ventricle in AO group, p = 0.04), and improved ST-segment resolution compared with normoxemic controls. CONCLUSIONS: Intracoronary hyperoxemic reperfusion was safe and well tolerated after PCI for AMI, but did not improve regional wall motion, ST-segment resolution, or final infarct size. A possible treatment effect was observed in anterior AMI patients reperfused <6 h of symptom onset.     

Effect of exercise on acute myocardial infarction in rats

Infarct expansion, the time-related thinning and dilation of an acute transmural infarct, leads to aneurysm formation and cardiac rupture in humans. In this study, the effect of exercise on acute infarct expansion early after myocardial infarction was examined in 129 rats. Ninety rats were exercised on a treadmill for 1.5 hours daily for 1 week beginning on the day of coronary artery ligation; the remaining 39 rats remained in their cages. There was no effect on the prevalence or extent of expansion; specifically, infarct wall thickness, left ventricular diameter and expansion grade (0 to 4+) were similar in the exercise and control rats. There was no difference in infarct size or the number of animals with aneurysmal shape changes in the exercise and control groups. There was no significant difference between the two groups in the histologic finding of intramural hemorrhage, a feature that has been associated with cardiac rupture, and no complete rupture was seen. However, there was a nonsignificant trend toward higher mortality in the exercised group. Thus, the findings of this study suggest that moderate exercise early after myocardial infarction produces no significant detrimental effect on infarct size or left ventricular topography in the rat model.     

Infarct resorption, compensatory hypertrophy, and differing patterns of ventricular remodeling following myocardial infarctions of varying size

OBJECTIVES: We sought to identify advantages of contrast-enhanced magnetic resonance imaging (MRI) in studying postinfarction ventricular remodeling. BACKGROUND: Although sequential measurements of ventricular volumes, internal dimensions, and total ventricular mass have provided important insights into postinfarction left ventricular remodeling, it has not been possible to define serial, directionally opposite changes in resorption of infarcted tissue and hypertrophy of viable myocardium and effects of these changes on commonly used indices of remodeling. METHODS: Using gadolinium-enhanced MRI, the time course and geometry of changes in infarcted and noninfarcted regions were assessed serially in dogs subjected to coronary occlusion for 45 min, 90 min, or permanently. RESULTS: Infarct mass decreased progressively between three days and four to eight weeks following coronary occlusion; terminal values averaged 24 +/- 3% of those at three days. Radial infarct thickness also decreased progressively, whereas changes in circumferential and longitudinal extent of infarction were variable. The ability to define the circumferential endocardial and epicardial extents of infarction allowed radial thinning without epicardial expansion to be distinguished from true infarct expansion. The mass of noninfarcted myocardium increased by 15 +/- 2% following 90-min or permanent occlusion. However, the time course of growth of noninfarcted myocardium differed systematically from that of infarct resorption. Measurements of total ventricular mass frequently failed to reflect concurrent changes in infarcted and noninfarcted regions. Reperfusion accelerated infarct resorption. Histologic reductions in nucleus-to-cytoplasm ratios corresponded with increases in noninfarcted ventricular mass. CONCLUSIONS: Concurrent directionally opposite changes in infarcted and noninfarcted myocardium can be defined serially, noninvasively, and with high spatial resolution and full ventricular coverage following myocardial infarction.     

经冠脉移植骨髓单个核细胞和间充质干细胞治疗急性心肌梗死的对比实验研究

目的 对比研究经冠脉骨髓单个核细胞（BM-MNC）和间充质干细胞（MSC）移植对实验性急性心肌梗死（AMI）心功能的影响及其机制.方法 选用12只雄性冀中白猪随机分为：正常对照组、AMI模型组、BM-MNC组、MSC组各3只,经导管球囊封闭前降支制作AMI的动物模型,于梗死后1 h直接冠脉球囊成型术后经OTW球囊注入骨髓干细胞.分别于术前及术后4 w经心脏超声检测心功能,4 w后取材行光、电镜病理学检查,实时定量RT-PCR检测心肌血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）mRNA表达.结果 4 w时干细胞组比AMI模型组室壁运动异常指数显著减轻（P＜0.05）、射血分数显著提高（P＜0.01）.与AMI模型组相比：BM-M;NC和MSC组梗死区及梗死边缘区血管数显著增多、BM-MNC组增加比MSC组显著（P＜0.01）,心肌细胞凋亡指数显著降低,BM-MNC组及MSC组间无明显差异（P＜0.01）.干细胞移植组梗死边缘区冠脉血管周围可见异常细胞生长,有毛细血管＂芽生＂现象,可见不成熟的心肌细胞和细胞凋亡.4 w时左室射血分数（LVEF）与心肌血管数成正相关（r=0.694 9,P=0.037 7）,LVEF与心肌细胞凋亡指数成负相关（r=0.913 3,P=0.000 6）.BM-MNC组,心肌梗死区及梗死边缘区VEGF基因表达比其他三组均明显增加（梗死区F=4.23,P=0.045 6,边缘区F=5.66,P=0.022 3）.BM-MNC及MSC组心肌梗死区bFGF基因表达比梗死模型组显著增加（梗死区F=7.49,P=0.010 4）.结论 经冠脉骨髓单个核细胞和间充质干细胞移植均可改善实验性AMI心功能;改善心功能的机理与梗死区及梗死边缘区VEGF及bFGF表达增加,血管密度增加,心肌细胞凋亡减少有关;骨髓单个核细胞移植的促血管增生作用优于间充质干细胞移植.     

不同月龄鼠急性心肌梗死后心室重构和心脏破裂的观察

目的 探讨老龄对小鼠急性心肌梗死(AMI)后心室重构心脏破裂的影响. 方法 老龄和低龄C57BL/6小鼠,随机分为假手术组、心肌梗死组.建立AMI模型后,观察心脏破裂发生率,并于AMI后第7天行超声和血流动力学检查;应用酶谱法、病理染色及免疫组化方法 ,分别于AMI后第3、7天检测基质金属蛋白酶-2、-9(MMP-2、MMP-9)活性表达,炎性细胞浸润程度,心肌间质胶原含量(CVF)和类型的变化. 结果 AMI后老龄组心脏破裂率高于低龄组(38.0%与16.0%,X2=6.139,P＜0.05);第7天时,较低龄组出现明显的梗死区扩张、左心室重构、心功能障碍及血流动力学变化(t=5.754,P＜0.05).与低龄组比较,老龄AMI组AMI后第3天炎性细胞浸润程度、MMP-9表达明显增加(P＜0.05).与低龄组比较,老龄组心肌间质胶原含量、Ⅲ型胶原表达增加(P＜0.05). 结论 老龄是小鼠AMI后心脏破裂的高危因素,其原因可能与AMI早期炎性细胞浸润程度增加、MMP-9、Ⅲ型胶原过度表达和早期左心室重构恶化有关.     

Macroscopic hemorrhagic infarction following selective coronary thrombolysis in acute myocardial infarction

Macroscopic hemorrhagic infarction was studied in 14 autopsied hearts with selective coronary thrombolysis (SCT) after acute myocardial infarction (AMI). In all patients urokinase, 240,000 - 720,000 units, had been selectively injected into ischemia-related coronary artery at 2 - 7 hours after the onset of AMI. The degree of stenosis after SCT was 90 - 99% in 13 patients and 100% in one patient. According to the duration of illness at death, the 14 patients were classified into 3 stages; stage I: 4 - 9 hours; stage II: 15 hours to 11 days; stage III: 19 days to 12 months. Three hearts in stage I had no macroscopic hemorrhage. In stage II, marked and diffuse hemorrhage in the infarct area was macroscopically evident in 6 of 7 hearts. In a stage II patient, extravasation of contrast medium into the myocardium was found at 3 hours after the onset of AMI. In stage III, 4 hearts had massive fibrosis or granulation in the left ventricular wall without macroscopic hemorrhage. Cardiac rupture was seen in 4 of 10 patients from stages I and II. It is concluded that macroscopic bleeding appears in most patients with AMI treated with coronary thrombolysis. In the majority of cases, the hemorrhage increases gradually after SCT and becomes macroscopically definite approximately 15 hours after the onset of AMI. Rarely, massive bleeding appears earlier. Hemorrhagic infarction is replaced by massive fibrosis after approximately 2 weeks.     

Immediate mineralocorticoid receptor blockade improves myocardial infarct healing by modulation of the inflammatory response

Mineralocorticoid receptor (MR) blockade reduces morbidity and mortality after acute myocardial infarction; however, the underlying mechanisms are still under investigation. This study examined whether MR antagonism promotes healing of the infarcted myocardium. Starting immediately after coronary ligation, male Wistar rats were treated with the selective MR antagonist eplerenone (100 mg/kg per day by gavage) or placebo for 2 to 7 days. At 7 days, eplerenone therapy versus placebo significantly reduced thinning and dilatation of the infarcted wall, improved left ventricular function, and enhanced neovessel formation in the injured myocardium. At 2 days, eplerenone-treated rats displayed lower plasma corticosterone levels, higher circulating blood monocytes, and more macrophages infiltrating the infarcted myocardium. MR blockade led to a transient upregulation (at days 2 and 3 but not at day 7) of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interleukin-4 and an increase in factor XIIIa protein expression in the healing myocardium. Prevention of macrophage accumulation into the infarct zone by treatment with liposome-encapsulated clodronate almost abrogated the protein expression of factor XIIIa and the beneficial effects of eplerenone on infarct expansion. In conclusion, selective MR blockade immediately after myocardial infarction accelerated macrophage infiltration and transiently increased the expression of healing promoting cytokines and factor XIIIa in the injured myocardium resulting in enhanced infarct neovascularization and reduced early LV dilation and dysfunction.     

The Relationship between Collateral Blood Flow and Infarct Zone Regional Wall Motion in Patients with Recent Acute Myocardial Infarction

After acute myocardial infarction (AMI), the most significant prognostic determinants of myocardial viability and function are deterioration degree of the distal myocardial microcirculation and collateral flow. Quantification of coronary collateral circulation is possible by using intracoronary pressure measurement techniques. We hypothesized that quantitatively determined coronary wedge pressure (CWP) and collateral flow index (CFI) may be useful in order to designate regional left ventricular function and indirectly viability after MI. In this study, we investigated the relationships between angiographically quantified wall motion scores and CWP and CFI in patients with recent AMI and treated with thrombolytic therapy. Forty patients early after myocardial infarction with 60% residual stenosis in infarct related artery (IRA) after thrombolysis, who underwent PTCA and/or stent implantation for this culprit lesion, were included in this study. None of the patients had significant stenosis in other coronary arteries. Angiographic ventricular wall motion scoring (WMS) was performed semi quantitatively according to coronary artery surgery study criteria. After angiography, fiberoptic pressure monitoring guide wire (pressure wire, Radi) was positioned distal to the stenosis to be dilated. During complete occlusion with balloon inflation distal pressure recorded as CWP. CFI was determined as the ratio of simultaneously measured CWP to aortic pressure. The mean values of CWP, CFI and mean WMS were 18.1 ± 7.9 mmHg, 0.18 ± 0.09 and 3.15 ± 0.8, respectively. The CWP (r: –0.86) and CFI (r: –0.84) values correlated well with WMS determined in the infarcted territory. We concluded that collateral circulation in the infarcted region is related to the left ventricular regional function. Presence of adequate and intact collateral network in the infarct related segments diminishes microvascular damage translating into preserved left ventricular regional functions.     

Differences of global and regional left ventricular function in anterior and inferior myocardial infarction: assessment by the use of a regional ejection fraction

Radionuclide angiography was performed on 41 patients with transmural myocardial infarction (MI) [17: anterior MI, 24: inferior MI] and 10 normal subjects in order to evaluate the influence of the infarct site on the global and the regional left ventricular function. The severity of the wall motion abnormality agreed closely with the reduction in the relative regional ejection fraction (%REF). The depression of the left ventricular ejection fraction (LVEF) in anterior MI was greater than that in inferior MI (p less than 0.01). We also found that the depression of the performance in the infarcted zone in anterior MI was more marked than that in inferior MI (p less than 0.01). However, function in the non-infarcted zone was almost the same in the anterior MI as in the inferior MI. As to the extent of the hypokinetic area, there was no significant difference between the patients with anterior MI and those with inferior MI. The above results indicated that the infarct site is an important determinant of the regional and the global left ventricular function after MI.     

Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion

Dilatation of infarcted segments (infarct expansion) may occur during recovery from myocardial infarction, but the fate of noninfarcted segments is uncertain. Accordingly, left ventricular geometric changes were assessed by left ventricular angiography and M mode echocardiography on admission and 2 weeks later in 30 patients with their first acute transmural myocardial infarction. All patients demonstrated chest pain, ST segment elevation with subsequent development of Q waves (15 anterior, 15 inferior), and elevation of cardiac enzymes. Sequential left ventricular angiographic and hemodynamic findings were available in these patients by virtue of their participation in a study of thrombolysis in acute myocardial infarction. By that study design, all patients treated successfully with thrombolytic therapy and demonstrating improvement of flow in an occluded coronary artery underwent repeat cardiac catheterization. At 2 weeks there was a significant decrease in left ventricular and pulmonary capillary wedge pressures (p less than .01), whereas both left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume indexes increased (p less than .01). The increase in LVEDV correlated directly with the percentage of the ventriculographic silhouette that was akinetic or dyskinetic at the initial catheterization (r = .71, p less than .001). To assess regional changes in both infarcted and noninfarcted segments, serial endocardial perimeter lengths of both the akinetic-dyskinetic segments (infarction zone) and of the remainder of the cardiac silhouette (noninfarction zone) were measured in all patients who demonstrated at least a 20% increase in their LVEDV at 2 weeks after myocardial infarction. Notably, there was a mean increase of 13% in the endocardial perimeter length of infarcted segments and a 19% increase in the endocardial perimeter length of noninfarcted segments. Serial M mode echocardiographic studies showed no significant change in the wall thickness of noninfarcted myocardial segments. Hemodynamic changes that occurred in this subgroup of patients included significant decreases in left ventricular end-diastolic and pulmonary capillary wedge pressures (p less than .05) and significant increases in angiographic cardiac index (p less than .01) and LVESV index (p less than .01). We conclude that in patients who manifest cardiac dilatation in the early convalescent period after myocardial infarction, there is remodeling of the entire left ventricle including infarct expansion of akinetic-dyskinetic segments and volume-overload hypertrophy of noninfarcted segments.(ABSTRACT TRUNCATED AT 400 WORDS)     

Myocardial healing and repair after experimental infarction in the rabbit

Adequacy of healing after acute myocardial infarction may determine the incidence of postmyocardial infarction rupture and ventricular aneurysm. Accordingly, in 36 rabbits, from 1 to 8 days after coronary ligation, and in 18 shams, we measured collagen formation and mechanical resistance of the infarcted left ventricle to stretch and rupture. Prolyl hydroxylase, an intracellular enzyme of collagen synthesis, increased from control activity of 3970 +/- 431 to 9224 +/- 643 counts/min per mg (cpm/mg) extractable protein (P less than 0.01) at 48 hours and was nearly maximal at 3 days postmyocardial infarction (14,518 +/- 2,030 cpm/mg, P less than 0.01). Lysyl oxidase, an extracellular collagen cross-linkage enzyme, increased from control activity of 29.6 +/- 4.8 to 74.7 +/- 18.8 cpm/mg extractable protein (P less than 0.01) at 72 hours and peaked at 121.5 +/- 7.3 (P less than 0.01) 4-6 days postmyocardial infarction. Hydroxyproline, a measure of collagen content, increased from control of 2.8 +/- 0.2 to 5.3 +/- 0.6 mg/g dry weight (P less than 0.05) at 72 hours and continued to increase at 8 days postmyocardial infarction (14.5 +/- 1.7 mg/g dry weight; P less than 0.01). When enzyme activities and hydroxyproline content were expressed relative to other reference bases, including DNA, tissue protein, dry weight, and total left ventricle, similar results were obtained. The mechanical properties of the infarcted left ventricle were determined by filling a balloon in the excised left ventricle until rupture. The rupture threshold in the normal left ventricle, [664 +/- 43 mm Hg (n = 16)], was not significantly different from that of the infarcted left ventricle on days 1-8 postmyocardial infarction. However, left ventricular rupture occurred more often through the myocardial infarction on days 1-4 postmyocardial infarction (59%) than on days 6 and 8 (18%; P = 0.03) when collagen content had significantly increased. Wall stress at the point of rupture in left ventricles from shams and normals was 30 +/- 2 g/mm2; tensile strength in isolated left ventricle muscle strips was 25 +/- 4 g/mm2 and in isolated scar strips at 7 days postmyocardial infarction was 59 +/- 7 g/mm2. The passive stiffness of the infarcted left ventricle increased from control of 61 +/- 5 to 94 +/- 6 mm Hg/100 microliters (P less than 0.05) at 4 days and 100 +/- 7 mm Hg/100 microliters (P less than 0.01) at 6 days postmyocardial infarction. Stiffness correlated with hydroxyproline content over the 8 days postmyocardial infarction (r = 0.599; P less than 0.001). Thus, the acutely infarcted ventricle was highly resistant to rupture during the initial 48 hours postmyocardial infarction, before any increase in collagen occurred. This result suggests that the preinfarction collagen content has an important role in preventing rupture. After 72 hours postmyocardial infarction, collagen synthesis appeared to be a determinant of infarct stiffness and resistance of the infarcted ventricle to rupture.     

Post-myocardial infarction ventricular remodeling: Animal and human studies

Summary Segmental alterations in left ventricular function are generally present in patients who suffer an acute myocardial infarction. Regional wall motion abnormalities in left ventricular systolic function can be identified in the hyperacute period and generally persist in patients who complete a myocardial infarction. Through the process of infarct expansion, the infarcted territory may thin and lengthen in the short term following a myocardial infarction. Some infarct survivors are also prone to further progressive alterations in the shape and size of the left ventricle, a process that has been termedpostinfarction ventricular remodeling. Although left ventricular remodeling appears to represent an adaptive process serving to preserve stroke volume (and cardiac output) following myocardial injury, the enlargement process may have undesirable long-term effects on global left ventricular function and on clinical prognosis. Fortunately, recent experimental and clinical evidence demonstrates that ventricular remodeling and its deleterious consequences may be preventable.     

Left ventricular systolic function in myocardial infarction survivors treated with primary angioplasty, thrombolysis of angioplasty preceded by thrombolysis

BACKGROUND. Acute myocardial infarction (AMI) may be treated with thrombolysis, primary angioplasty or a combination of both methods. Preservation of left ventricular systolic function is an important goal of treatment. AIM. To assess whether the mode of treatment of AMI influences left ventricular systolic function measured 6 months after AMI. METHODS. In a group of 108 patients who survived AMI, an echocardiographic examination was performed 6 months afterwards. Ejection fraction, wall motion score index, asynergy area index, infarcted wall motion score index and apical segments motion score index were measured. Patients were divided into three groups: those treated with thrombolysis only, treated with angioplasty or those who underwent angioplasty preceded by thrombolysis. RESULTS. Global left ventricular systolic function was similar in all three groups. Compared to the two remaining groups, the group treated with combined therapy had significantly worse indexes of infarcted wall motion score and apical segments motion score. This group also included a significantly higher number of patients with akinetic or dyskinetic apical segments. CONCLUSIONS. Echocardiographic examination of global left ventricular systolic function in MI survivors performed 6 months after AMI, reveals similar values regardless of the method used for AMI treatment. However, segmental systolic function in the area of infarcted wall and apical segments is significantly more altered in patients treated with angioplasty preceded by thrombolysis than in other analysed patients.     

Impact of plaque rupture on infarct size in ST-segment elevation anterior acute myocardial infarction.

OBJECTIVES: We sought to assess whether coronary plaque rupture at culprit lesions is associated with infarct size in patients with anterior acute myocardial infarction (AMI). BACKGROUND: Some patients with AMI have large infarcts despite early reperfusion. Whether culprit plaque morphology impacts infarct size or not remains unknown. METHODS: Patients who had a first anterior AMI with reperfusion within 6 hours after onset were enrolled and divided into 2 groups according to the presence or absence of plaque rupture at the culprit lesion as defined by preintervention intravascular ultrasound (IVUS): patients with rupture (n = 54) and without rupture (n = 37). RESULTS: Patients with plaque rupture had a higher incidence of no-reflow phenomenon (15% vs. 3%; p = 0.08) and a lower myocardial blush grade (1.5 vs. 2.3; p < 0.05) after percutaneous coronary intervention. The IVUS analysis showed that patients with plaque rupture had a higher incidence of soft plaque and positive remodeling. Peak creatine kinase levels were higher (4,707 vs. 2,309 IU/l; p < 0.0001) and left ventricular ejection fraction in the chronic phase was lower (54% vs. 63%; p < 0.01) in patients with plaque rupture. A multivariate logistic regression analysis revealed that plaque rupture and the proximal lesion site correlated with a left ventricular ejection fraction of <50% in the chronic phase (odds ratios 6.5 and 17.5, respectively; p < 0.05). CONCLUSIONS: Plaque rupture is associated with morphologic characteristics of vulnerable lesions, as well as with larger infarcts and a higher incidence of no-reflow phenomenon, suggesting that plaque embolism contributes to the progression of myocardial damage in patients with anterior AMI.