Objectives: The purpose of this study was to study aging-associated alterations in the inflammatory and reparative response after myocardial infarction MI and their involvement in adverse post-infarction remodeling of the senescent heart. Background: Advanced age is a predictor of death and ventricular dilation in patients with MI; however, the cellular mechanisms responsible for increased remodeling of the infarcted senescent heart remain poorly understood.
Methods: Histomorphometric, molecular, and echocardiographic end points were compared between young and senescent mice undergoing reperfused infarction protocols. The response of young and senescent mouse cardiac fibroblasts to transforming growth factor TGF -beta stimulation was examined. Results: Senescence was associated with decreased and delayed neutrophil and macrophage infiltration, markedly reduced cytokine and chemokine expression in the infarcted myocardium, and impaired phagocytosis of dead cardiomyocytes.
Reduced inflammation in senescent mouse infarcts was followed by decreased myofibroblast density and markedly diminished collagen deposition in the scar. The healing defects in senescent animals were associated with enhanced dilative and hypertrophic remodeling and worse systolic dysfunction. Fibroblasts isolated from senescent mouse hearts showed a blunted response to TGF-beta1. Conclusions: Although young mice exhibit a robust post-infarction inflammatory response and form dense collagenous scars, senescent mice show suppressed inflammation, delayed granulation tissue formation, and markedly reduced collagen deposition.
Expression and Implication of Clusterin in Left Ventricular Remodeling After Myocardial Infarction
These defects might contribute to adverse remodeling. These observations suggest that caution is necessary when attempting to therapeutically target the post-infarction inflammatory response in patients with reperfused MI. The injurious potential of inflammatory mediators might have been overstated, owing to extrapolation of experimental findings from young animals to older human patients.
Abstract Objectives: The purpose of this study was to study aging-associated alterations in the inflammatory and reparative response after myocardial infarction MI and their involvement in adverse post-infarction remodeling of the senescent heart. Publication types Research Support, N.However, its role in the pathophysiology of left ventricular LV remodeling after myocardial infarction MI remains unresolved.
Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis. Myocardial infarction MI commonly triggers left ventricular LV remodeling, progressive deterioration of cardiac function, and ultimately, the clinical syndrome of heart failure HF .
However, current understanding of the pathophysiologic mechanisms of LV remodeling is still fragmentary. Although increased tissue expression of CTGF in disease is often associated with fibrosis it is not yet known to what extent CTGF causes fibrosis. Thus, despite the unresolved role of elevated myocardial CTGF activities in heart failure, myocardial CTGF expression may reflect both fibrosis and functional derangement of the heart. A recent study reported preserved cardiac function in transgenic mice with cardiac-restricted overexpression of CTGF following chronic infusion of angiotensin II .
However, to what extent the cardioprotective effects of CTGF are maintained in chronic ischemia, infarct healing and LV remodeling remain to be investigated. Cardiac-restricted expression of CTGF resulted in minimal increase of myocardial fibrosis per seand indicated that, at the least, additional co-factors are required for CTGF to stimulate relevant fibrosis .
All animal studies were performed in accordance with the NIH Guidelines for the Use of Laboratory Animals and were approved by the institutional and national boards for laboratory animal research. The patient study was approved by the Regional Ethics Committee of Western Norway and all patients provided written informed consent prior to inclusion.
The mice were immobilized on a heating pad and subjected to left-sided thoracotomy between the third and fourth intercostal space.
Pallor of the affected myocardium ensured ischemia. The study end-point was 4 weeks 28 days after induction of MI. Cardiac dimensions and cardiac function were assessed by a high-resolution ultrasonography system VevoVisualSonics Inc. At study end-point, LV function was also assessed by trans-carotid catheterization of the left ventricle and continuous recording of LV pressure, as previously described .
LV sections were subjected to computerized planimetry in order to determine the area of non-perfused myocardial tissue. After 24 hours the mice were euthanized by cardioplegic arrest following infusion of KCl. Histochemistry and morphometric analysis of myocardial sections, determination of myocardial mRNA levels by real-time qPCR, Western blot analysis, and assay of myocardial hydroxyproline contents were performed as previously described .
The cross-sectional area of cardiac myocytes was determined in transverse sections of the left ventricle after staining of plasma membrane with rhodamine-labeled wheat germ agglutinin WGA Vector Laboratories, Inc. The cross-sectional area of individual myocytes was determined by digital planimetry using the Adobe Photoshop software. Cruz Biotechnology, Inc.
Venous blood samples were collected in pyrogen-free ethylenediaminetetraacetic acid EDTA -containing tubes or tubes without any additives at the time of the CMR examinations, at day 2, 1 week, 2 months and 1 year following PCI. The tubes were subsequently centrifuged at x g for 10 min for preparation of plasma and serum samples, respectively. Categorical variables are expressed as proportions and comparisons were made by two-sided Chi-Square test. Survival analysis was evaluated with Kaplan-Meier curves and compared by log-rank test.
Intra-group changes in the CMR parameters during follow-up were analyzed with the Friedman test. As shown in Fig. Histogram demonstrating area at risk in the left ventricles of NLC and Tg-CTGF mice determined by computerized planimetry after excision of the hearts.
Histogram demonstrating infarct size area of necrosis relative to area at risk 24 hours after ligation of LAD, determined as described in the Materials and Methods section. NLC group.
Infarct size, i. NLC: Cardiac dimensions at baseline assessed by transthoracic echocardiography were similar among the groups. In NLC mice subjected to MI, normalized lung weights were substantially increased at study end-point compatible with pulmonary congestion. In contrast, Tg-CTGF mice did not display significant alterations of lung weights from baseline to study end-point.Background: Left ventricular remodeling LVR after myocardial infarction is associated with an increased risk of heart failure and death.
In spite of a modern therapeutic approach, LVR remains relatively frequent and difficult to predict in clinical practice. Our aim was to identify new biomarkers of LVR and understand their involvement in its development.
Methods and results: Proteomic analysis of plasma from the REVE-2 study Remodelage Ventriculaire -a study dedicated to the analysis of LVR which included patients after a first anterior myocardial infarction-identified increased plasma levels of CLU clusterin in patients with high LVR. We used a rat model of myocardial infarction to analyze CLU expression in the LV and found a significant increase that was correlated with LVR parameters.
We found increased CLU expression and secretion in primary cultures of rat neonate cardiomyocytes hypertrophied by isoproterenol. Conclusions: Our results show for the first time that plasma CLU levels are associated with LVR post-myocardial infarction, have in part a cardiac origin, and are a predictor of early death in heart failure patients. Keywords: biomarkers; clusterin; heart failure; proteomic; survivors. Abstract Background: Left ventricular remodeling LVR after myocardial infarction is associated with an increased risk of heart failure and death.
Publication types Research Support, Non-U.As more patients survive myocardial infarctions, the incidence of heart failure increases. Specifically, this paper will examine the neurohormonal activity of the renin—angiotensin—aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets.
Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed.
Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future. This is a preview of subscription content, log in to check access. Rent this article via DeepDyve. Survival in patients with reduced left ventricular ejection fraction and congestive heart failure-treatment trial.
Circulation 76 1 — Cohn JN, Ferrari R, Sharpe N Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. JACC 35 3 — Circulation — Two different complications of acute myocardial infarction.
Am J Cardiol — A corollary to infarct expansion. Circ Res 67 1 — In: Mann D ed Heart failure. Saunders, Philadelphia, pp — Google Scholar. Heart Fail Rev 14 4 — Circ Res — J Mol Cell Cardiol — Lancet — Circulation 2 — Groenning BA, Nilsson JC, Sondergaard L et al Anti-remodeling effects on left ventricle during beta-blockade with Metoprolol in treatment of chronic heart failure.
JACC 36 7 — J Pharmacol Exp Ther 1 — Maczewski M, Borys M, Kacprzak P et al Angiotensin II AT1 receptor density on blood platelets predicts early left ventricular remodeling in non-reperfused acute myocardial infarction in humans. Eur J Heart Fail 8 2 — Maczewski M, Borys M, Kacprzak P et al Late ventricular remodeling in non-reperfused acute myocardial infarction in humans is predicted by angiotensin II type 1 receptor density on blood platelets.
Int J Card — Results of the survival and ventricular enlargement trial SAVE. NEJM 10 — NEJM 25 — NEJM 5 — NEJM 20 — Circulation 10 — Oishi Y, Ozono R et al AT2 receptor mediates the cardioprotective effects of AT1 receptor antagonist in post-myocardial infarction remodeling.Background: The association of left ventricular remodeling LVR after myocardial infarction MI with the subsequent risk of heart failure HF and death has not been studied in patients receiving optimal secondary prevention.
Methods and results: We performed a long-term clinical follow-up of patients included in 2 prospective multicentric studies on LVR after first anterior MI. Median clinical follow-up after LVR assessment was Similar results were obtained when cardiovascular death was considered as an isolated endpoint. After adjustement on baseline characteristics including ejection fraction, the association with the composite endpoint was unchanged.
Conclusion: In a context of a modern therapeutic management with a large prescription of evidence-based medications, LVR remains independently associated with HF and cardiovascular death at long-term follow-up after MI. Abstract Background: The association of left ventricular remodeling LVR after myocardial infarction MI with the subsequent risk of heart failure HF and death has not been studied in patients receiving optimal secondary prevention.Eugene Braunwald, MD: Acute MI to Heart Failure: The Past, Present, and Future
Grant support. This work was supported by grants from the E. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The aim of this study was to investigate the effect of no-reflow phenomenon on ventricular systolic synchrony via myocardial blush grades MBGs in patients with acute anterior myocardial infarction after percutaneous coronary intervention PCI.
All patients were divided into two groups and assessed by MBGs. To observe the parameters of the left ventricular function and left ventricular systolic synchrony, equilibrium radionuclide angiography was performed 1 week after PCI and repeated 6 months after acute myocardial infarction AMI. A multivariate regression analysis was performed to assess the contribution of confounding factors.
A total of patients were enrolled in this study: 26 in the no-reflow and 74 in the reflow group. There was no significant difference in terms of age, sex, hypertension history, diabetes history, hyperlipidemia history, and smoking history between the two groups.
The no-reflow phenomenon identified by MBGs reflects the no-reperfusion status in the myocardium in the infarction-related zone after AMI. The directly caused reduction in the left ventricular systolic synchrony performance leads to adverse long-term outcomes in patients with AMI. The purpose of the treatment strategy for acute myocardial infarction AMI is to rescue the dying heart tissues by completely opening the occluded blood vessels.
Thus, once the diagnosis of AMI is made, the initiation of reperfusion therapy with primary percutaneous coronary intervention PCI is one of the early and effective management plans.
Meanwhile, the use of myocardial blush grades MBGs for the assessment of myocardial reperfusion in AMI after PCI has been established as an effective and clinically feasible approach. The effect of no-reflow phenomenon on ventricular systolic synchrony was studied by the application of the computer-assisted equilibrium blood-pool imaging approach. A total of patients 67 males and 33 females, aged They were admitted to The Second Hospital of Hebei Medical University from October to October and were treated directly with urgent PCI within 12 hours after the first onset of the symptoms of acute anterior myocardial infarction.
Inclusion criteria were: 1 first onset of AMI; 2 diagnosis made in accordance with the WHO diagnostic criteria; 3 PCI performed within 12 hours after the onset of symptoms; and 4 voluntary participation.
Written informed consent was obtained from all the participants. A complete range of images with the optimal projection angle and effects were selected and assessed by MBG criteria. MBG was determined by two experienced physicians using the MBG method: 7 grade 0: no contrast agent in the infarction-related zone IRZ of the myocardium; grade 1: mild staining with contrast agent of the myocardium in IRZ, but significantly lower than that of the myocardium in the ipsilateral or contralateral non-IRZ; grade 2: moderate staining of the myocardium in IRZ with the contrast agent, but lower than that of the myocardium in the ipsilateral or contralateral non-IRZ; grade 3: normal staining of the myocardium, referring to staining in the IRZ of the myocardium with an extent of the contrast agent identical to that in the ipsilateral or contralateral non-IRZ side.
According to the no-reflow MBG standards, patients with an MBG within the range 0—1 were classified as the no-reflow group, and as the reflow group when the MBG was 2—3. One week and 6 months after PCI, all patients underwent ERNA using a DST digital signal technology dual-head SPECT single photon emission computed topography computer system Sopha, Buc, Cedex, Franceand parameters, such as left ventricular systolic function, diastolic function, and synchronization function, were obtained automatically through the software in the computer.
The patients were followed up for 6 months for major complications and major cardiovascular events, including postinfarction angina, reinfarction, heart failure, cerebrovascular accident, vital organs bleeding, puncture site hematoma, and death. ERNA-related parameter measurements were conducted by two nuclear medicine physicians. Statistical analysis was performed using software SPSS A multivariate regression analysis was employed to assess the implications of confounding factors.
The flowchart of the study design is illustrated in Figure 1. There were 26 patients in the no-reflow group 17 males and nine females, mean age No significant difference in age, sex, hypertension history, diabetes history, hyperlipidemia history, and smoking history was observed between the two groups.
However, in the no-reflow group, the interval between symptom onset and balloon time was significantly longer than that in the reflow group 9. Notes: Comparison between no-reflow and reflow groups. We found that no-reflow identified by MBG reflects the no-reperfusion status in the myocardium in the post-AMI IRZ, causing directly a decrease in left ventricular systolic synchrony performance with adverse long-term outcomes in patients with AMI.
The aim of reperfusion treatment of AMI by PCI is to quickly and fully restore myocardial blood flow to avoid further myocardial necrosis and dysfunction; therefore, the incidence of no-reflow after PCI affects the efficacy of clinical treatment. TIMI grade 3 blood flow has been revealed to indicate only that the velocity of blood flow in the large epicardial vessels and branches has reached a normal level.Adaptations of the aging left ventricle LV to hemodynamic overload are functionally and structurally distinct from those of the young organism.
This study describes the influence of aging on LV hemodynamics and remodeling late after myocardial infarction MI in Fischer Brown Norway rats. Isometric myocardial function was evaluated in papillary muscles of and mo-old sham rats.
Myocardial systolic function was decreased in older rats. To determine how aging affects LV function and remodeling after MI, rats were infarcted at 7 and 18 mo of age and were studied 5 mo later.
Heart failure after myocardial infarction: clinical implications and treatment
Infarct size was similar in each group. However, there were no significant differences between young and older rats in any variable of LV systolic function or remodeling after MI. After MI, myocardial fibrosis was significantly increased from baseline only in younger rats. The negative interaction of aging and MI on myocyte hypertrophy and fibrosis was highly significant. The findings indicate that baseline LV and myocradial function decline with age. In the aging rat after MI, despite limited compensatory hypertrophy and more advanced baseline myocardial fibrosis, the long-term functional and structural adaptations to MI are similar to those of the mature adult heart.
Abstract Adaptations of the aging left ventricle LV to hemodynamic overload are functionally and structurally distinct from those of the young organism. Publication types Research Support, Non-U.
Gov't Research Support, U. Gov't, Non-P. Research Support, U.