scholarly journals Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
D. S. Mansell ◽  
V. D. Bruno ◽  
E. Sammut ◽  
A. Chiribiri ◽  
T. Johnson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Circumferential Strain ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Large Animal ◽  
Strain Rates ◽  
Ventricular Remodelling ◽  
Tissue Levels ◽  
Over Time

AbstractTo identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5–6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

scholarly journals Regional Changes in Myocardial Strain Predict Ventricular Remodelling after Myocardial Infarction in a Large Animal Model

2021 ◽  
Author(s):  
Doyin S. Mansell ◽  
Vito D. Bruno ◽  
Eva Sammut ◽  
Amedeo Chiribiri ◽  
Tom Johnson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Circumferential Strain ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Large Animal ◽  
Strain Rates ◽  
Ventricular Remodelling ◽  
Early Predictors ◽  
Over Time

Abstract To identify early predictors of late left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used. LVR was assessed by cardiac magnetic resonance imaging (CMRI) at baseline, 12–48 hours (acute), and 5–6 weeks (chronic) post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories,21 of which correlated with LV equatorial circumferential strain rate (ECSR). The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2 (CG-RP-2), and secreted frizzled-related protein 1 (sFRP1). Results indicate that early changes in regional peak ACS predict late LV remodelling and LVR post-MI is associated with augmented levels of D-3PGDH and sFRP1, which show the strongest association with peak ECSR. These findings might help to prevent LVR post-MI by influencing/directing LV unloading strategies or by pharmacological control of tissue levels of D-3PGDH and sFRP1.

scholarly journals Delivery of a matrix metalloproteinase-responsive hydrogel releasing TIMP-3 after myocardial infarction: effects on left ventricular remodeling

2018 ◽  
Vol 315 (4) ◽  
pp. H814-H825 ◽  
Author(s):  
Brendan P. Purcell ◽  
Shayne C. Barlow ◽  
Paige E. Perreault ◽  
Lisa Freeburg ◽  
Heather Doviak ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Matrix Metalloproteinases ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Left Ventricular Geometry ◽  
Relative Reduction ◽  
Large Animal ◽  
Early Reperfusion ◽  
Localized Delivery

Although improvements in timing and approach for early reperfusion with acute coronary syndromes have occurred, myocardial injury culminating in a myocardial infarction (MI) remains a common event. Although a multifactorial process, an imbalance between the induction of proteolytic pathways, such as matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinase (TIMPs), has been shown to contribute to this process. In the present study, a full-length TIMP-3 recombinant protein (rTIMP-3) was encapsulated in a specifically formulated hyaluronic acid (HA)-based hydrogel that contained MMP-cleavable peptide cross-links, which influenced the rate of rTIMP-3 release from the HA gel. The effects of localized delivery of this MMP-sensitive HA gel (HAMMPS) alone and containing rTIMP-3 (HAMMPS/rTIMP-3) were examined in terms of the natural history of post-MI remodeling. Pigs were randomized to one of the following three different groups: MI and saline injection (MI/saline group, 100-μl injection at nine injection sites, n = 7), MI and HAMMPS injection (MI/HAMMPS group; 100-μl injection at nine injection sites, n = 7), and MI and HAMMPS/rTIMP-3 injection (MI/HAMMPS/rTIMP-3 group; 20-μg/100-μl injection at nine injection sites, n = 7). Left ventricular (LV) echocardiography was serially performed up to 28 days post-MI. LV dilation, as measured by end-diastolic volume, and the degree of MI wall thinning were reduced by ~50% in the HAMMPS/rTIMP-3 group ( P < 0.05). Furthermore, indexes of heart failure progression post-MI, such as LV filling pressures and left atrial size, were also attenuated to the greatest degree in the HAMMPS/rTIMP-3 group. At 28 days post-MI, HAMMPS/rTIMP-3 caused a relative reduction in the transcriptional profile for myofibroblasts as well as profibrotic pathways, which was confirmed by subsequent histochemistry. In conclusion, these findings suggest that localized delivery of a MMP-sensitive biomaterial that releases a recombinant TIMP holds promise as a means to interrupt adverse post-MI remodeling. NEW & NOTEWORTHY The present study targeted a myocardial matrix proteolytic system, matrix metalloproteinases (MMPs), through the use of a recombinant tissue inhibitor of MMPs incorporated into a MMP-sensitive hydrogel, which was regionally injected using a large animal model of myocardial infarction. Left ventricular geometry and function and indexes of myocardial remodeling were improved with this approach and support the advancement of localized therapeutic strategies that specifically target the myocardial matrix.

Bioengineering Quantification of Left Ventricular Remodeling Following Myocardial Infarction

2009 ◽  
Author(s):  
Changfu Wu ◽  
Won-Bae Chang ◽  
Marc Gibber ◽  
P. Griffith Bartley ◽  
Zhongjun J. Wu
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Western World ◽  
Large Animal ◽  
Lv Remodeling ◽  
Geometric Changes

Myocardial infarction (MI)-induced heart failure is the prevailing cause of morbidity and mortality in the western world. It is the sequela of the deleterious left ventricular (LV) remodeling process. So far, the mechanisms of the cardiac remodeling process are not completely understood. A clinically relevant large animal model is an essential vehicle for studying the mechanisms of cardiac remodeling. In our laboratory, we have developed a reproducible ovine model of post-infarct chronic cardiac remodeling. Throughout the study period of an animal, the functional and geometric changes of the LV were monitored by echocardiographic and bioengineering means.

scholarly journals A novel method of standardized myocardial infarction in aged rabbits

2017 ◽  
Vol 312 (5) ◽  
pp. H959-H967 ◽  
Author(s):  
Patrick J. Morrissey ◽  
Kevin R. Murphy ◽  
Jean M. Daley ◽  
Lorraine Schofield ◽  
Nilufer N. Turan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Minimally Invasive ◽  
Left Ventricular ◽  
Ventricular Free Wall ◽  
Large Animal Model ◽  
Large Animal ◽  
Free Wall ◽  
Left Ventricular Free Wall ◽  
Invasive Approach ◽  
Age Cohorts

The incidence of both myocardial infarction (MI) and sudden cardiac death increases with age. Here, we describe the development of a minimally invasive large animal model of MI that can be applied to young or aged animals. We demonstrate that rabbit coronary anatomy is highly variable, more so than described in previous literature. In this work, we categorize the coronary pattern of 37 young rabbits and 64 aged rabbits. Aged rabbits had a higher degree of branching from the left main coronary artery. Standardizing the model across age cohorts required a new approach, targeting an area of myocardium rather than a specific vessel. Here, we present a method for achieving a reproducible infarct size, one that yielded a consistent scar encompassing ~30% of the apical left ventricular free wall. The model’s consistency allowed for more valid comparisons of MI sequelae between age cohorts. NEW & NOTEWORTHY This study describes the coronary angiographic imaging of young and aged rabbits. We developed and improved a novel minimally invasive approach for coil embolization that targets a specific area of myocardium and yielded a consistent scar encompassing ~30% of the left ventricular free wall of young and aged rabbit hearts.

scholarly journals Cardiovascular magnetic resonance-determined left ventricular myocardium impairment is associated with C-reactive protein and ST2 in patients with paroxysmal atrial fibrillation

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Lei Zhao ◽  
Songnan Li ◽  
Chen Zhang ◽  
Jie Tian ◽  
Aijia Lu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Healthy Subjects ◽  
T1 Mapping ◽  
Circumferential Strain ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Native T1

Abstract Background Myocardial strain assessed with cardiovascular magnetic resonance (CMR) feature tracking can detect early left ventricular (LV) myocardial deformation quantitatively in patients with a variety of cardiovascular diseases, but this method has not yet been applied to quantify myocardial strain in patients with atrial fibrillation (AF) and no coexistent cardiovascular disease, i.e., the early stage of AF. This study sought to compare LV myocardial strain and T1 mapping indices in AF patients and healthy subjects, and to investigate the associations of a portfolio of inflammation, cardiac remodeling and fibrosis biomarkers with LV myocardial strain and T1 mapping indices in AF patients with no coexistent cardiovascular disease. Methods The study consisted of 80 patients with paroxysmal AF patients and no coexistent cardiovascular disease and 20 age- and sex-matched healthy controls. Left atrial volume (LAV), LV myocardial strain and native T1 were assessed with CMR, and compared between the AF patients and healthy subjects. Biomarkers of C-reactive protein (CRP), transforming growth factor beta-1 (TGF-β1), collagen III N-terminal propeptide (PIIINP), and soluble suppression of tumorigenicity 2 (sST2) were obtained with blood tests, and compared between the AF patients and healthy controls. Associations of these biomarkers with those CMR-measured parameters were analyzed for the AF patients. Results For the CMR-measured parameters, the AF patients showed significantly larger LAV and LV end-systolic volume, and higher native T1 than the healthy controls (max P = 0.027). The absolute values of the LV peak systolic circumferential strain and its rate as well as the LV diastolic circumferential strain rate were all significantly reduced in the AF patients (all P < 0.001). For the biomarkers, the AF patients showed significantly larger CRP (an inflammation biomarker) and sST2 (a myocardium stiffness biomarker) than the controls (max P = 0.007). In the AF patients, the five CMR-measured parameters of LAV, three LV strain indices and native T1 were all significantly associated with these two biomarkers of CRP and sST2 (max P = 0.020). Conclusions In patients with paroxysmal AF and no coexistent cardiovascular disease, LAV enlargement and LV myocardium abnormalities were detected by CMR, and these abnormalities were associated with biomarkers that reflect inflammation and myocardial stiffness.

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