Postinfarction Cardiac Rupture Research Articles

Colchicine Prevents Cardiac Rupture in Mice with Myocardial Infarction by Inhibiting P53-Dependent Apoptosis.

Cardiac rupture is a fatal complication following myocardial infarction (MI) and there are currently no effective pharmacological strategies for preventing this condition. In this study, we investigated the effect of colchicine on post-infarct cardiac rupture in mice and its underlying mechanisms.We induced MI in mice by permanently ligating the left anterior descending artery. Oral colchicine or vehicle was administered at a dose of 0.1 mg/kg/day from day 1 to day 7 after MI. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with colchicine.Colchicine significantly improved the survival rate (colchicine, n = 46: 82.6% versus vehicle, n = 42: 61.9%, P < 0.05) at 1 week after MI. Histological analysis revealed colchicine significantly reduced the infarct size and the number of macrophages around the infarct area. Colchicine decreased apoptosis in the myocardium of the border zone and cultured cardiomyocytes and fibroblasts as assessed by TUNEL assay. Colchicine also attenuated the activation of p53 and decreased the expression of cleaved-caspase 3 and bax, as assessed by Western blotting.Colchicine prevents cardiac rupture via inhibition of apoptosis, which is attributable to the downregulation of p53 activity. Our findings suggest that colchicine may be a prospective preventive medicine for cardiac rupture, however, large clinical trials are required.

P222 POSTINFARCT CARDIAC FREE WALL RUPTURE DETECTED BY CARDIAC CT

Abstract A 57–years–old man with a history of smoke and hypertension was transferred to our unit with chest pain and dyspnoea, lasting few days. Electrocardiography revealed the presence of ST elevation in the infero–lateral leads with Q waves and Transthoracic Echocardiographic Study revealed a normal dimension left ventricle with infero–postero–lateral akinesia, moderately reduced EF (40%) in the absence of significant valve disease and an organized pericardial effusion of about one centimetre. In the meantime, the first signs of hemodynamic instability and cardiogenic shock appeared and the ETT revealed the exacerbation of the pericardial effusion. So we did an emergency coronary angiography that revealed a calcified three–vessel disease with occlusion of the middle segment of Cx. Because of the worsening of the cardiogenic shock we used the aortic balloon pump to improve the hemodynamic instability. The concomitant presence of signs of late infarction, pericardial effusion and cardiogenic shock make us suspect a myocardial rupture so we did a cardiac computed tomography (CT ) scan that was suggestive for a cardiac wall rupture within the infarcted left ventricle. The patient was urgently transported to the cardiac surgery room where the patch of inferior wall was performed and then was transferred to the Intensive Care Unit. After the surgery, a residual of pericardial effusion persisted without hemodynamic significant and the revascularization was planned one month after discharge. Heart rupture represents a mechanical complication of MI that we have to suspect every time we find signs of myocardial infarction and pericardial effusion that degenerate into cardiogenic shock. Although it occurs in a very limited number of cases, the postinfarct cardiac free wall rupture is characterized by a poor prognosis and cardiac Computed Tomography provides primary information for the diagnosis.

Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of nonreperfused myocardial infarction.

In patients with myocardial infarction (MI), cardiac rupture is an uncommon but catastrophic complication. In the mouse model of nonreperfused MI, reported rupture rates are highly variable and depend not only on the genetic background and sex of animals but also on the method used for documentation of rupture. In most studies, diagnosis of cardiac rupture is based on visual inspection during autopsy; however, criteria are poorly defined. We performed systematic histopathological analysis of whole hearts from C57BL/6J mice dying after nonreperfused MI and evaluated the reliability of autopsy-based criteria in identification of rupture. Moreover, we compared the cell biological environment of the infarct between rupture-related and rupture-independent deaths. Histopathological analysis documented rupture in 50% of mice dying during the first week post-MI. Identification of a gross rupture site was highly specific but had low sensitivity; in contrast, hemothorax had high sensitivity but low specificity. Mice with rupture had lower myofibroblast infiltration, accentuated macrophage influx, and a trend toward reduced collagen content in the infarct. Male mice had increased mortality and higher incidence of rupture. However, infarct myeloid cells harvested from male and female mice at the peak of the incidence of rupture had comparable inflammatory gene expression. In conclusion, the reliability of autopsy in documentation of rupture in infarcted mice is dependent on the specific criteria used. Macrophage-driven inflammation and reduced activation of collagen-secreting reparative myofibroblasts may be involved in the pathogenesis of post-MI cardiac rupture.NEW & NOTEWORTHY We show that cardiac rupture accounts for 50% of deaths in C57BL/6J mice undergoing nonreperfused myocardial infarction protocols. Overestimation of rupture events in published studies likely reflects the low specificity of hemothorax as a criterion for documentation of rupture. In contrast, identification of a gross rupture site has high specificity and low sensitivity. We also show that mice dying of rupture have increased macrophage influx and attenuated myofibroblast infiltration in the infarct. These findings are consistent with a role for perturbations in the balance between inflammatory and reparative responses in the pathogenesis of postinfarction cardiac rupture. We also report that the male predilection for rupture in infarcted mice is not associated with increased inflammatory activation of myeloid cells.

Pathomorphological characteristics of myocardial infarction complicated by rupture

The report presents the results of a pathoanatomical study of 81 cases of postinfarction cardiac rupture. The terms of development of cardiac rupture and comorbid background of patients are specified. Inconsistences of in vivo diagnostics of both ischemic heart disease and comorbid diseases, the results of autopsies were revealed.

Post-Infarct Cardiac Free Wall Rupture Detected by Multi-Detector Computed Tomography

Post-Infarct Cardiac Free Wall Rupture Detected by Multi-Detector Computed Tomography

PostInfarct Cardiac Free Wall Rupture Detected by Multidetector Computed Tomography

1. Abstract 48-year-old lady with chest pain is diagnosed to have aninfer posterior MI. 2decho reveals a moderate pericardial effusion post thrombolysis with persistent chest pain. Inview of a possibility of a sealed myocardial rupture she undergoes a coronary CTA to assess the coronary anatomy and to delineate the rupture. The CTA confirms the rupture and delineates the coronary anatomy. Patient undergoes pericardial patch repair with a good result. 2. Keywords: M ultidetector Computed Tomography; Myocardial Rupture

Topiramate modulates post-infarction inflammation primarily by targeting monocytes or macrophages

Monocytes/macrophages response plays a key role in post-infarction inflammation that contributes greatly to post-infarction ventricular remodelling and cardiac rupture. Therapeutic targeting of the GABAA receptor, which is enriched in monocytes/macrophages but not expressed in the myocardium, may be possible after myocardial infarction (MI). After MI was induced by ligation of the coronary artery, C57BL/6 mice were intraperitoneally administered with one specific agonist or antagonist of the GABAA receptor (topiramate or bicuculline), in the setting of presence or depletion of monocytes/macrophages. Our data showed that within the first 2 weeks after MI, when monocytes/macrophages dominated, in contrast with bicuculline, topiramate treatment significantly reduced Ly-6Chigh monocyte numbers by regulating splenic monocytopoiesis and promoted foetal derived macrophages preservation and conversion of M1 to M2 or Ly-6Chigh to Ly-6Clow macrophage phenotype in the infarcted heart, though GABAAergic drugs failed to affect M1/M2 or Ly-6Chigh/Ly-6Clow macrophage polarization directly. Accordingly, pro-inflammatory activities mediated by M1 or Ly-6Chigh macrophages were decreased and reparative processes mediated by M2 or Ly-6Clow macrophages were augmented. As a result, post-infarction ventricular remodelling was attenuated, as reflected by reduced infarct size and increased collagen density within infarcts. Echocardiographic indices, mortality and rupture rates were reduced. After depletion of monocytes/macrophages by clodronate liposomes, GABAAergic drugs exhibited no effect on cardiac dysfunction and surrogate clinical outcomes. Control of the GABAA receptor activity in monocytes/macrophages can potently modulate post-infarction inflammation. Topiramate emerges as a promising drug, which may be feasible to translate for MI therapy in the future.

Long-term outcome and risk prediction in patients suffering acute myocardial infarction complicated by post-infarction cardiac rupture

BackgroundPost-infarction cardiac rupture (CR) such as ventricular septal rupture (VSR), free wall rupture (FWR), atrial septal rupture (ASR) or papillary muscle rupture (PMR) is a rare but dreaded complication in patients with acute myocardial infarction (AMI) associated with a very poor prognosis with reported mortality rates between 60 and 100%. Therefore suitable risk stratification for secondary prevention seems crucial, but data on long-term survival und risk prediction in this especially vulnerable patient collective remains scarce. MethodsOut of 11,641 patients presenting with AMI a total of 28 individuals suffering post-infarction CR were identified and stratified in “acute survivors of CR” (n=10) and “non-survivors of CR” (n=18). Cox regression hazard analysis was used to assess prognosticators on long-term survival. ResultsTen patients (35.7%) survived the initial event. After a median follow-up time of 9years 2 (20%) of the survivors died, both due to cardiovascular causes. Younger age (p=0.023) and higher systolic blood pressure at admission (p=0.018) turned out to be significant predictors of long-term survival. Systolic blood pressure 48h after CR proved to be a strong and independent predictor for survival with an adjusted hazard ratio per one standard deviation of 0.89 (95% CI: 0.72–0.99; 0.048). ConclusionHemodynamic stabilization and severity of cardiogenic shock were detected as clinically most common among patients suffering post-infarction CR and proved to be of major importance for survival. If survival of the initial event was achieved, satisfying long-term mortality could be reached.

Hypertension and sudden cardiac death: their relationship in postinfarction cardiac rupture

The incidence and distribution of primary glomerulonephropathies vary throughout the world and by race and ethnicity. We sought to evaluate the distribution of primary glomerulonephropathies among a large racially and ethnically diverse population of the United States.Case series from January 1, 2000, through December 31, 2011.Adults (aged ≥ 18 years) of an integrated health system who underwent native kidney biopsy and had kidney biopsy findings demonstrating focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and other.Rates and characteristics of the most common primary glomerulonephropathies overall and by race and ethnicity.2,501 patients with primary glomerulonephropathy were identified, with a mean age 50.6 years, 45.7% women, 36.1% Hispanics, 31.2% non-Hispanic whites, 17.4% blacks, and 12.4% Asians. FSGS was the most common glomerulonephropathy (38.9%) across all race and ethnic groups, followed by MGN (12.7%), MCD (11.0%), IgAN (10.2%), and other (27.3%). The FSGS category had the greatest proportion of blacks, and patients with FSGS had the highest rate of poverty. IgAN was the second most common glomerulonephropathy among Asians (28.6%), whereas it was 1.2% among blacks. Patients with MGN presented with the highest proteinuria (protein excretion, 8.3 g) whereas patients with FSGS had the highest creatinine levels (2.6 mg/dL). Overall glomerulonephropathy rates increased annually in our 12-year observation period, driven by FSGS (2.7 cases/100,000) and IgAN (0.7 cases/100,000). MGN and MCD rates remained flat.Missing data for urine albumin and sediment, indication bias in performing kidney biopsies, and inexact classification of primary versus secondary disease.Among a racially and ethnically diverse cohort from a single geographical area and similar environment, FSGS was the most common glomerulonephropathy, but there was variability of other glomerulonephropathies based on race and ethnicity.

Olmesartan prevents cardiac rupture in mice with myocardial infarction by modulating growth differentiation factor 15 and p53.

Cardiac rupture is a catastrophic complication that occurs after acute myocardial infarction (MI) and, at present, there are no effective pharmacological strategies for preventing this condition. Here we investigated the effect of the angiotensin II receptor blocker olmesartan (Olm) on post-infarct cardiac rupture and its underlying mechanisms of action. C57Bl/6 mice with MI were treated with Olm, aldosterone (Aldo) or vehicle. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with angiotensin II (Ang II), RNH6270 (active ingredient of Olm) or Aldo. The mortality rate and incidence of cardiac rupture in MI mice during the first week in the Olm-treated group were significantly lower than in the vehicle-treated group. Olm or RNH6270 reduced myeloperoxidase staining in the infarcted myocardium, decreased apoptosis in cultured cardiomyocytes and fibroblasts, as assessed by Hoechst staining and TUNEL assay, attenuated the accumulation of p53 and phosphorylated p53 and cleaved caspase 3 induced by MI or Ang II, as assessed by Western blotting, and up-regulated growth differentiation factor-15 (GDF-15). In cultured cardiomyocytes and fibroblasts, treatment with Ang II, Aldo or anoxia significantly down-regulated the expression of GDF-15. Olm prevents cardiac rupture through inhibition of apoptosis and inflammation, which is attributable to the down-regulation of p53 activity and up-regulation of GDF-15. Our findings suggest that early administration of an AT1 receptor anatagonist to patients with acute MI is a potential preventive approach for cardiac rupture.

Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction

Myocardial infarction (MI) provokes regional inflammation which facilitates the healing, whereas excessive inflammation leads to adverse cardiac remodelling. Our aim was to determine the role of macrophage migration inhibitory factor (MIF) in inflammation and cardiac remodelling following MI. Wild type (WT) or global MIF deficient (MIFKO) mice were subjected to coronary artery occlusion. Compared to WT mice, MIFKO mice had a significantly lower incidence of post-MI cardiac rupture (27% vs. 53%) and amelioration of cardiac remodelling. These were associated with suppressed myocardial leukocyte infiltration, inflammatory mediators' expression, and reduced activity of MMP-2, MMP-9, p38 and JNK MAPK. Infarct myocardium-derived or exogenous MIF mediated macrophage chemotaxis in vitro that was suppressed by inhibition of p38 MAPK or NF-κB. To further dissect the role of MIF derived from different cellular sources in post-MI cardiac remodelling, we generated chimeric mice with MIF deficiency either in bone marrow derived-cells (WTKO) or in somatic-cells (KOWT). Compared to WT and KOWT mice, WTKO mice had reduced rupture risk and ameliorated cardiac remodelling, associated with attenuated regional leukocyte infiltration and expression of inflammatory mediators. In contrast, KOWT mice had delayed healing and enhanced expression of M1 macrophage markers, but diminished expression of M2 markers during the early healing phase. In conclusion, global MIF deletion protects the heart from post-infarct cardiac rupture and remodelling through suppression of leukocyte infiltration and inflammation. Leukocyte-derived MIF promotes inflammatory responses after MI, whereas cardiac-derived MIF affects early but not ultimate healing process.

Abstract 9857: Inhibition of Endoplasmic Reticulum Stress Prevents Cardiac Rupture and Attenuates Cardiac Remodeling by Alleviating Mitochondrial Apoptosis and Nlrp3 Inflammasome Activation

Background: Endoplasmic reticulum (ER) stress is involved in myocardial ischemia, but its role and underlying mechanism in the pathogenesis of post-infarct cardiac rupture and remodeling remain unclear. It is known that mitochondrial apoptosis and NLRP3 inflammasome activation are associated with tissue necrosis and fibrosis, which are crucial for cardiac rupture and remodeling. Here we hypothesized that ER stress promotes cardiac rupture and remodeling by increasing mitochondrial apoptosis and NLRP3 inflammation activation. Methods and Results: Left coronary ligation was used to produce myocardial infarction (MI) in C57BL/6 mice. There was 37.5% cardiac rupture rate in the control group during the early phase of MI (2-7 days). The survivals underwent cardiac remodeling and formed ventricular aneurysm with impaired systolic and diastolic functions at the end of 4 weeks. The rupture rate was significantly decreased to 20% in the 4-PBA intraperitoneal injection group (20 mg/kg/day) and the heart functions were improved at the end of 4 weeks. Furthermore, the ventricular aneurysm and myocardial fibrosis were much smaller. Western blot showed that the ER stress markers, mitochondrial bax, caspase 3, NLRP3, TGFβ1 and Smad 2 in the heart tissues of control group were significantly increased after MI, in which mitochondrial bax and caspase 3 were increased markedly in the early phase of MI (3 days), while NLRP3, TGFβ1 and Smad 2 were increased obviously in the late phase of MI (3-28 days). 4-PBA decreased those protein levels in the early and late phases of MI respectively. Then ER stress was induced in neonatal rat’s cardiomyocytes and fibroblasts by 3% hypoxia stimulation for 3 days. Calcein plus CoCL 2 , flow cytometry for JC-1 and western blot for mitochondrial bax and caspase 3 indicated that 4-PBA (0.5 mM) pretreatment protects the cardiomyocytes against mitochondrial-dependent apoptosis induced by hypoxia. Meanwhile, western blot showed that the expression of NLRP3, TGFβ1 and Smad 2 in the fibroblasts were increased by hypoxia stimulation but decreased by 4-PBA. Conclusion: Inhibition of ER stress is a novel therapeutic strategy for preventing post-infarct cardiac rupture and attenuating cardiac remodeling.

GW24-e2374 Deficiency in Fractalkine Receptor Reduces Post-infarction Cardiac Rupture

ObjectivesOur previous studies have demonstrated that fractalkine (FKN) promotes myocardial inflammation and fibrosis which are known to might play a crucial role in post-infarction cardiac rupture. However, it is completely...

Sutureless repair for postinfarction cardiac rupture: A simple approach with a tissue-adhering patch

Sutureless repair for postinfarction cardiac rupture: A simple approach with a tissue-adhering patch

EComment. The patch and glue technique with or without TachoSil(R)?

I read with great interest the paper by Pocar and colleagues regarding the use of TachoSil® (Nycomed, Zurich, Switzerland) as a modification of the classic patch and glue sutureless repair for left ventricular free wall rupture secondary to myocardial infarction [1]. They successfully treated three patients with postinfarction free wall rupture using cardiopulmonary bypass without cardiac arrest. Instead of applying the glue directly on the infarction area and then covering it with a biological or synthetic patch, they initially applied several layers of a fibrinogen/thrombin-coated collagen patch on the oozing surface of the heart [1].The authors stated that no false aneurysm was observed during the follow-up period, however the duration of the follow-up in this paper is unclear. In 1988, Padro and colleagues [2] reported the first case of postinfarction cardiac rupture successfully treated with a sutureless technique using a Teflon patch and biocompatible glue. Since then, many alternatives have been described in the literature to cover myocardial perforations, involving Teflon, Dacron, Goretex or pericardial patches and different biological glues [3]. Encouraging results of the sutureless technique without the use of TachoSil® have led some authors to advocate the patch and glue repair over the classic infarcectomy repair [4].The patch and glue technique is considered simple, safe and effective, but the number of patients treated is limited with different techniques. Another major drawback of this technique is the absence of long-term imaging follow-up results. Recently, Zoffoli and colleagues [5] reported no early or late myocardial ruptures (mean follow-up of 6.7 years) at the treatment site in 25 consecutive patients with postinfarction cardiac rupture. Others have published less favourable results with 37% (3 out of 8 patients) developing aneurysms at the site of the repair [3]. Long-term follow-up is important to determine whether this technique is promising and durable. Close imaging follow-up is paramount in this patient population.

How Aldosterone Can Break Your Heart

Aldosterone promotes postinfarction cardiac rupture through the oxidation of the kinase CaMKII.

Patch-and-glue repair in combination with or without direct suture for cardiac rupture after myocardial infarction

Left ventricular free-wall rupture is a catastrophic event after myocardial infarction. The most appropriate surgical management remains controversial. We have performed a patch-and-glue technique, with or without direct suture and using cardioplegic arrest, to treat postinfarction cardiac rupture. We describe our experiences over a 5-year period, and discuss the optimal surgical repair for each type of rupture. Since 2002, we have managed 5 patients with cardiac rupture. Two patients had a blowout rupture, 2 were of the subacute type, and 1 experienced an oozing rupture. There were 3 men and 2 women, with an average age of 76.2 +/- 12.5 years. Echocardiography confirmed the diagnosis in all patients. Two patients underwent a patch-and-glue repair in combination with direct suture, one had an infarctectomy, and the others had a completely sutureless patch-and-glue treatment performed using cardioplegic arrest. All patients survived the initial treatment and were moved to the intensive care unit with complete hemostasis. The 2 patients who were treated in combination with direct suture died of brain death or cardiac failure (mortality rate 40%). The 3 patients who were treated with the patch-and-glue sutureless technique were discharged from our hospital, and are alive 15-27 months after the operation. Two are doing well, and the other is breathing on his own but remains nonreactive. We prefer the patch-and-glue sutureless technique even for a blowout rupture. We performed cardioplegic arrest to provide a bloodless surgical field and maximize adhesive function. The whole necrotic area should be covered with a large patch of appropriate size.

Age-related differences in post-infarct cardiac rupture and LV remodeling associated with MMPs activation

The mechanisms responsible for age-related post-MI cardiac rupture are unknown. Method and results: Male C57BL mice, aging at 3 and 12 months were subjected to MI and followed up to day-7 after surgery. Old mice had a significantly higher incidence of rupture than young mice (40.7% vs. 18.3%, P=0.013) despite a similar infarct size between the two groups (47±2 vs. 44±4%). Echocardiography showed that AMI for 7 days resulted in more severe LV dysfunction (FS% 80% vs. 64%), LV wall thinning (posterior wall thickness%, 18% vs.

Age-Related Differences in Post-Infarct Cardiac Rupture and LV Remodelling Associated with MMPs Activation

Age-Related Differences in Post-Infarct Cardiac Rupture and LV Remodelling Associated with MMPs Activation

Age-related Differences in Post-infarct Cardiac Rupture and LV Remodelling Associated with MMPs Activation

Age-related Differences in Post-infarct Cardiac Rupture and LV Remodelling Associated with MMPs Activation