Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model.
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ABSTRACT:
SUBMITTER: Mansell DS
PROVIDER: S-EPMC8443552 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Heart failure continues to be a common and deadly sequela of myocardial infarction (MI). Despite strong evidence suggesting the importance of myocardial mechanics in cardiac remodelling, many MI studies still rely on two-dimensional analyses to estimate global left ventricular (LV) function. Here, we integrated four-dimensional ultrasound with three-dimensional strain mapping to longitudinally characterize LV mechanics within and around infarcts in order to study the post-MI remodelling process. To induce infarcts with varying severities, we separated 15 mice into three equal-sized groups: (i) sham, (ii) 30 min ischaemia-reperfusion, and (iii) permanent ligation of the left coronary artery. Four-dimensional ultrasound from a high-frequency small animal system was used to monitor changes in LV geometry, function and strain over 28 days. We reconstructed three-dimensional myocardial strain maps and showed that strain profiles at the infarct border followed a sigmoidal behaviour. We also identified that mice with mild remodelling had significantly higher strains in the infarcted myocardium than those with severe injury. Finally, we developed a new approach to non-invasively estimate infarct size from strain maps, which correlated well with histological results. Taken together, the presented work provides a thorough approach to quantify regional strain, an important component when assessing post-MI remodelling.
| S-EPMC6893492 | biostudies-literature
Project description:In this work, we present a method to assess left ventricle (LV) regional function from cardiac magnetic resonance (CMR) imaging based on the regional ejection fraction (REF) and regional area strain (RAS). CMR scans were performed for 30 patients after first-time myocardial infarction (MI) and nine age- and sex-matched healthy volunteers. The CMR images were processed to reconstruct three-dimensional LV geometry, and the REF and RAS in a 16-segment model were computed using our proposed methodology. The method of computing the REF was tested and shown to be robust against variation in user input. Furthermore, analysis of data was feasible in all patients and healthy volunteers without any exclusions. The REF correlated well with the RAS in a nonlinear manner (quadratic fit-R(2) = 0.88). In patients after first-time MI, the REF and RAS were significantly reduced across all 16 segments (REF: p < 0.05; RAS: p < 0.01). Moreover, the REF and RAS significantly decreased with the extent of transmural scar obtained from late gadolinium-enhanced CMR images. In addition, we show that the REF and RAS can be used to identify regions with compromised function in the patients with preserved global ejection fraction with reasonable accuracy (more than 78%). These preliminary results confirmed the validity of our approach for accurate analysis of LV regional function. Our approach potentially offers physicians new insights into the local characteristics of the myocardial mechanics after a MI.
| S-EPMC4387531 | biostudies-other
Project description:AIMS:Acute myocardial infarction (MI) is the major cause of chronic heart failure. The activity of blood coagulation factor XIII (FXIIIa) plays an important role in rodents as a healing factor after MI, whereas its role in healing and remodelling processes in humans remains unclear. We prospectively evaluated the relevance of FXIIIa after acute MI as a potential early prognostic marker for adequate healing. METHODS AND RESULTS:This monocentric prospective cohort study investigated cardiac remodelling in patients with ST-elevation MI and followed them up for 1 year. Serum FXIIIa was serially assessed during the first 9 days after MI and after 2, 6, and 12 months. Cardiac magnetic resonance imaging was performed within 4 days after MI (Scan 1), after 7 to 9 days (Scan 2), and after 12 months (Scan 3). The FXIII valine-to-leucine (V34L) single-nucleotide polymorphism rs5985 was genotyped. One hundred forty-six patients were investigated (mean age 58 ± 11 years, 13% women). Median FXIIIa was 118% (quartiles, 102-132%) and dropped to a trough on the second day after MI: 109% (98-109%; P < 0.001). FXIIIa recovered slowly over time, reaching the baseline level after 2 to 6 months and surpassed baseline levels only after 12 months: 124% (110-142%). The development of FXIIIa after MI was independent of the genotype. FXIIIa on Day 2 was strongly and inversely associated with the relative size of MI in Scan 1 (Spearman's ? = -0.31; P = 0.01) and Scan 3 (? = -0.39; P < 0.01) and positively associated with left ventricular ejection fraction: ? = 0.32 (P < 0.01) and ? = 0.24 (P = 0.04), respectively. CONCLUSIONS:FXIII activity after MI is highly dynamic, exhibiting a significant decline in the early healing period, with reconstitution 6 months later. Depressed FXIIIa early after MI predicted a greater size of MI and lower left ventricular ejection fraction after 1 year. The clinical relevance of these findings awaits to be tested in a randomized trial.
| S-EPMC7524135 | biostudies-literature
Project description:AimsAltered left ventricular (LV) haemodynamic forces (HDFs) have been associated with positive and negative remodelling after pathogenic or therapeutic events. We aimed to identify LV HDFs patterns associated with adverse LV remodelling (aLVr) in reperfused segment elevation myocardial infarction (STEMI) patients.Methods and resultsForty-nine acute STEMI patients underwent cardiac magnetic resonance (CMR) at 1 week (baseline) and after 4 months (follow-up). LV HDFs were computed at baseline from cine CMR long axis data sets, using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDFs distribution was evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio %). HDFs parameters were computed over the entire heartbeat, in systole and diastole. At baseline, aLVr patients had lower systolic L-S HDF (2.7 ± 0.9 vs. 3.6 ± 1%; P = 0.027) and higher diastolic L-S/A-B HDF ratio (28 ± 14 vs. 19 ± 6%; P = 0.03). At univariate logistic regression analysis, higher infarct size [odds ratio (OR) 1.05; 95% confidence interval (CI) 1.01-1.1; P = 0.04], higher L-S/A-B HDFs ratio (OR 1.1; 95% CI 1.01-1.2; P = 0.05) and lower L-S HDFs (OR 0.41; 95% CI 0.2-0.9; P = 0.04) were associated with aLVr at follow-up. In the multivariable logistic regression analysis, diastolic L-S/A-B HDF ratio remained the only independent predictor of aLVr (OR 1.1; 95% CI 1.01-1.2; P = 0.04).ConclusionsMisalignment of diastolic haemodynamic forces after STEMI is associated with aLVr after 4 months.
| S-EPMC8787983 | biostudies-literature
Project description:We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported. Keywords: heart attack, mouse, time course, regional responses We report temporal and regional changes in steady state mRNA levels in the mouse LV following a surgically-induced AMI. Three regions of the infarcted LV were surveyed: IF, FW and IVS. For each region, mRNA levels were assayed at t=0 and six time points after occlusion of the left anterior descending coronary artery (t = 15 min, 1 h, 4 h, 12 h, 24 h, 48 h). As control, an identical time course was carried out in the mouse LV after sham surgery in which the suture was passed under the artery, but not ligated. For sham surgical mice and naïve mice (t=0), the IVS and the LV free wall were harvested and assayed. The AMI and sham time courses were repeated for a total of two independent repetitions of the experiment. For each repetition, 96 GeneChips were hybridized. Thus, for two repetitions, 192 GeneChips (2 x 96) were hybridized. In addition, the naïve time point was assayed a second time during Repetition 1 for six additional GeneChips (two tissues x three chips). The overall total number of samples is 198 GeneChips (192 + 6). Total RNA was isolated from each individual tissue sample. Equal weights of total RNA from 4-10 mice were combined for each LV region, time point and treatment. Copy RNA mixtures were synthesized from each total RNA pool and hybridized to the Affymetrix GeneChip set MG U74 v2 (A, B, and C) that carries 36,899 probe sets. The global normalization of fluorescence emissions for the 198 GeneChips used in this study and their conversion to relative transcript concentrations measured in relative fluorescence units (RFU) was conducted using Robust Multi-array Averaging (RMA; www.bioconductor.org). Each of the 198 Accessions is titled as follows: time point / treatment / tissue, repetition, GeneChip. The additional assays of naïve mice in Repetition 1 are labeled “Naive2”.
2006-07-13 | E-GEOD-4648 | biostudies-arrayexpress
Project description:BackgroundExtracellular matrix (ECM) turnover plays an important role in left ventricular (LV) remodelling following myocardial infarction (MI). Cysteinyl cathepsins contribute to ECM catabolism in arterial diseases, suggesting their participation in post-MI remodelling.Methods and resultsLeft anterior descending artery ligation-induced MI in mice showed increased expression and activity of cathepsin S (CatS). Administration of a non-selective cathepsin inhibitor, E64d, aggravated LV dysfunction at 7 and 28 days post-MI. Mechanistic studies showed that E64d increased post-MI inflammatory cell accumulation and cytokine expression, but did not affect apoptosis or angiogenesis in infarcted myocardium. Furthermore, E64d suppressed TGF-β1-induced Smad2 and Smad3 activation and expression of fibronectin extra domain A (ED-A), an alternatively spliced fibronectin variant, and subsequently prevented cardiac fibroblast trans-differentiation into myofibroblast, which contributed to post-MI collagen and fibronectin synthesis and deposition. Consistently, selective inhibition or genetically determined deficiency of CatS also reduced myocardial Smad2 and Smad3 activation and ED-A fibronectin expression, thus suppressing fibroblast trans-differentiation and resulting in adverse collagen turnover and impaired cardiac function-recapitulating the findings in mice treated with E64d.ConclusionAlong with its established activities in ECM degradation, CatS plays novel roles in TGF-β1 signalling, myofibroblast trans-differentiation, and ECM protein synthesis, thereby regulating scar formation in the infarcted myocardium and preserving LV function after experimental MI.
| S-EPMC3778959 | biostudies-literature
Project description:We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported. Keywords: heart attack, mouse, time course, regional responses
2006-07-14 | GSE4648 | GEO
Project description:AimsFollowing a favourable pilot trial using a single bolus of ciclosporin, it has been unclear why 2 large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury and reduce infarct size in STEMI (ST elevation myocardial infarction). The purpose of this study was to assess the effect of ciclosporin on myocardial injury, left ventricular remodelling and lymphocyte kinetics in patients with acute STEMI undergoing primary percutaneous coronary intervention.MethodsIn this double-blind, single centre trial, we randomly assigned 52 acute STEMI patients with an onset of pain of <6 hours and blocked culprit artery to a single bolus of ciclosporin (n = 26) or placebo (n = 26, control group) prior to reperfusion by stent percutaneous coronary intervention. The primary endpoint was infarct size at 12 weeks.ResultsMean infarct size at 12 weeks was identical in both groups (9.1% [standard deviation= 7.0] vs 9.1% [standard deviation = 7.0], P = .99; 95% confidence interval for difference: -4.0 to 4.1). CD3 T-lymphocytes dropped to similar levels at 90 minutes (867 vs 852 cells/μL, control vs ciclosporin) and increased to 1454 vs 1650 cells/μL at 24 hours.ConclusionIn our pilot trial, a single ciclosporin bolus did not affect infarct size or left ventricular remodelling, matching the results from CYCLE and CIRCUS. Our study suggests that ciclosporin does either not reach ischaemic cardiomyocytes, or requires earlier application during first medical contact. Finally, 1 bolus of ciclosporin is not sufficient to inhibit CD4 T-lymphocyte proliferation during remodelling. We therefore believe that further studies are warranted. (Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention [CAPRI]; NCT02390674).
| S-EPMC7318996 | biostudies-literature
Project description:Thus far, the cellular and molecular mechanisms related to early (especially within 24 hours after acute myocardial infarct (MI)) exercise-mediated beneficial effects on MI have not yet been thoroughly established. In the present study, we demonstrated that acute MI rats that underwent early moderate exercise training beginning one day after MI showed no increase in mortality and displayed significant improvements in MI healing and ventricular remodelling, including an improvement in cardiac function, a decrease in infarct size, cardiomyocyte apoptosis, cardiac fibrosis and cardiomyocyte hypertrophy, and an increase in myocardial angiogenesis, left ventricular wall thickness and the number of cardiac telocytes in the border zone. Integrated miRNA-mRNA profiling analysis performed by the ingenuity pathway analysis system revealed that the inhibition of the TGFB1 regulatory network, activation of leucocytes and migration of leucocytes into the infarct zone comprise the molecular mechanism underlying early moderate exercise-mediated improvements in cardiac fibrosis and the pathological inflammatory response. The findings of the present study demonstrate that early moderate exercise training beginning one day after MI is safe and leads to significantly enhanced MI healing and ventricular remodelling. Understanding the mechanism behind the positive effects of this early training protocol will help us to further tailor suitable cardiac rehabilitation programmes for humans.
| S-EPMC6850916 | biostudies-literature
Project description:AimsLittle is known regarding factors that predict the occurrence of lethal ventricular arrhythmias (VAs) occurring after acute myocardial infarction (AMI). This observational cohort study aimed to identify factors that predicted lethal VAs during the late phase after AMI in patients with reduced left ventricular ejection fraction (LVEF).Methods and resultsData were collected from our AMI database regarding consecutive patients with an LVEF of ≤40% after AMI (January 2012 to July 2018). The 'late phase' was defined as ≥7 days after AMI onset, and the primary endpoint was defined as lethal VAs in the late phase. The study included 136 patients (82% men; mean age: 66 ± 13 years). The average LVEF at admission was 32.7 ± 8.2%. During a mean follow-up period of 20.7 months, 14 patients (10%) experienced lethal VAs, including ventricular fibrillation (n = 8) and sustained ventricular tachycardia (n = 10). Univariate analyses revealed that lethal VAs were predicted by age and LVEF at admission. Receiver operating characteristic curve analysis indicated that the optimal cut-off value was 23% for using the LVEF at admission to predict the primary endpoint (area under the curve: 0.77, P < 0.0001). Multivariable analysis also demonstrated that LVEF at admission was an independent predictor of the primary endpoint (risk ratio = 7.12, P = 0.001).ConclusionsLethal VAs in the late phase are common in patients with AMI, and reduced LVEF and cardiac function at admission play a significant role in the risk stratification for future lethal VAs in this population.
| S-EPMC8497219 | biostudies-literature