Abstract 18200: Intracoronary Delivery of Bioabsorbable Alginate Matrix (IK-5001) Ameliorates Adverse Post-infarction Left Ventricular Remodeling and Improves Left Ventricular Function in a Porcine Model of Reperfused Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Carlos G Santos-Gallego ◽  
Belén Picatoste ◽  
Ida U Njerve ◽  
Kiyotake Ishikawa ◽  
Jaime Aguero ◽  
...  
Keyword(s):  
Porcine Model ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Function ◽  
Contractile Reserve ◽  
Intracoronary Injection ◽  
Lv Remodeling

Background: Adverse cardiac remodeling after MI is associated with excessive degradation of the extracellular matrix (ECM). IK-5001 is a low viscosity injectable solution that provides the polysaccharide alginate. After intracoronary injection into the MI area it undergoes phase transition forming a hydrogel which can support the ECM. We hypothesized that administration of alginate post-MI would provide a temporary scaffold and attenuate adverse LV remodeling. Methods: Acute MI was induced in 16 pigs by balloon occlusion of the proximal LAD for 2 hours. Animals randomly received intracoronary alginate or saline 4 days post-MI. LV function and remodeling were evaluated with cardiac MRI, 3D-echo and pressure-volume loops at 1 and 2 months post-MI. Histology and Western blot analysis were performed after 2 months. Results: Both groups had similar LVEF and infarct size 4 days post-MI. Coronary angiography immediately after alginate injection showed no impairment in coronary flow. However, 2 months post-MI, alginate-treated pigs exhibited reduced LV remodeling compared with controls demonstrated by reduced LV end-systolic volume, LV mass and sphericity (Table). Alginate-treated pigs had less cardiomyocyte hypertrophy and decreased interstitial fibrosis. Consistent with this, chronic activation of Akt and ERK was reduced. Alginate pigs also showed lower plasma levels of BNP and aldosterone. Interestingly, after 2 months, alginate pigs showed better systolic LV function: higher LVEF, better contractile reserve with dobutamine, and higher dP/dt. Conclusions: Intracoronary administration of alginate ameliorates adverse post-MI LV remodeling at the anatomical, histological and molecular level, and mitigates neurohormonal activation in a porcine model of MI. Alginate also improves systolic LV function. Intracoronary injection of alginate represents an exciting novel treatment option to reduce post-MI remodeling that merits assessment in clinical studies.

scholarly journals Left-Ventricular Remodeling After Myocardial Infarction Is Associated with a Cardiomyocyte-Specific Hypothyroid Condition

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 669-679 ◽  
Author(s):  
Christine J. Pol ◽  
Alice Muller ◽  
Marian J. Zuidwijk ◽  
Elza D. van Deel ◽  
Ellen Kaptein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Luciferase Reporter ◽  
Cardiomyocyte Hypertrophy ◽  
In Vivo Measurement ◽  
Pathological Remodeling

Abstract Similarities in cardiac gene expression in hypothyroidism and left ventricular (LV) pathological remodeling after myocardial infarction (MI) suggest a role for impaired cardiac thyroid hormone (TH) signaling in the development of heart failure. Increased ventricular activity of the TH-degrading enzyme type 3 deiodinase (D3) is recognized as a potential cause. In the present study, we investigated the cardiac expression and activity of D3 over an 8-wk period after MI in C57Bl/6J mice. Pathological remodeling of the noninfarcted part of the LV was evident from cardiomyocyte hypertrophy, interstitial fibrosis, and impairment of contractility. These changes were maximal and stable from the first week onward, as was the degree of LV dilation. A strong induction of D3 activity was found, which was similarly stable for the period examined. Plasma T4 levels were transiently decreased at 1 wk after MI, but T3 levels remained normal. The high D3 activity was associated with increased D3 mRNA expression at 1 but not at 4 and 8 wk after MI. Immunohistochemistry localized D3 protein to cardiomyocytes. In vivo measurement of TH-dependent transcription activity in cardiomyocytes using a luciferase reporter assay indicated a 48% decrease in post-MI mice relative to sham-operated animals, and this was associated with a 50% decrease in LV tissue T3 concentration. In conclusion, pathological ventricular remodeling after MI in the mouse leads to high and stable induction of D3 activity in cardiomyocytes and a local hypothyroid condition.

Abstract 1706: Elevation of Pericardial Fluid Active Matrix Metalloproteinase-9 (MMP-9) Level Is Closely Associated With Left Ventricular Remodeling

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Shoichi Miyamoto ◽  
Moriaki Inoko ◽  
Kunihiko Nagai ◽  
Eisaku Nakane ◽  
Tomomi Abe ◽  
...  
Keyword(s):  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Active Form ◽  
Left Ventricular ◽  
Pericardial Fluid ◽  
Lv Function ◽  
Paracrine Factors ◽  
Lv Remodeling

Background: The development of congestive heart failure (CHF) is associated with left ventricular (LV) remodeling. However, fundamental mechanisms that contribute to this remodeling process remain unclear. The matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been demonstrated to play a significant role in tissue remodeling through a number of pathological processes. Objectives: The purpose of this study was to investigate whether MMPs and TIMPs represent autocrine/paracrine factors and are accumulated in pericardial fluid. We previously reported that active MMP-2 levels in pericardial fluid served as more sensitive and accurate indicators of LV remodeling than did active MMP-2 levels in plasma. Methods: We measured the concentrations of the enzyme (active MMP-9) in both plasma and pericardial fluid in 20 patients during coronary artery bypass graft surgery. Results: The active MMP-9 level was significantly higher in pericardial fluid than in plasma (4.68 ± 1.17 vs. 2.58 ± 0.29 ng/ml, p<0.0001). Interestingly, the pericardial fluid levels of active MMP-9 were significantly higher in patients with impaired LV function than in those with normal LV function (5.25 ± 0.57 vs. 2.96 ± 0.65 ng/ml, p<0.0001). Pericardial fluid active MMP-9 levels had closer relations with LVEDVI (r=0.459, p=0.047) and LVESVI (r=0.490, p=0.0321) than did plasma active MMP-9 levels (LVEDVI: r=0.065, p=NS; LVESVI: r=0.254, p=NS). Active MMP-9 levels in pericardial fluid but not in plasma inversely correlated with LV ejection fraction (r=−0.626, p=0.0033). Conclusions: Active MMP-9 levels in pericardial fluid serve as more sensitive and accurate indicators of LV remodeling than did active MMP-9 levels in plasma. Thus, active form of MMP-9 may be also secreted from the heart into the pericardial space with the progression of CHF, and it may have a pathophysiologic role in LV remodeling process as an autocrine/paracrine factor.

scholarly journals Assessment of the Utility of the SeptalE/(E′×S′)Ratio and Tissue Doppler Index in Predicting Left Ventricular Remodeling after Acute Myocardial Infarction

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Selma Kenar Tiryakioglu ◽  
Hakan Ozkan ◽  
Hasan Ari ◽  
Kıvanc Yalin ◽  
Senol Coskun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Doppler Echocardiography ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Tissue Doppler Echocardiography ◽  
Anterior Myocardial Infarction ◽  
Lv Remodeling ◽  
Group 1

Background. The aim of this study is to show whether the septalE/(E′×S′)ratio assessed by tissue Doppler echocardiography can predict left ventricular remodeling after first ST segment elevation myocardial infarction treated successfully with primary percutaneous intervention.Methods. Consecutive patients (n=111) presenting with acute anterior myocardial infarction for the first time in their life were enrolled. All patients underwent successful primary percutaneous coronary intervention. Standard and tissue Doppler echocardiography were performed in the first 24-36 hours of admission. Echocardiographic examination was repeated after 6 months to reassess left ventricular volumes. SeptalE/(E′×S′)ratio was assessed by pulsed Doppler echocardiography.Results. Group 1 consisted of 33 patients with left ventricular (LV) remodeling, and Group 2 had 78 patients without LV remodeling.E/(E′×S′)was significantly higher in Group 1 (4.1±1.9versus1.65±1.32,p=0.001). The optimal cutoff value forE/(E′×S′)ratio was 2.34 with 87.0% sensitivity and 82.1% specificity.Conclusion. SeptalE/(E′×S′)values measured after the acute anterior myocardial infarction can strongly predict LV remodeling in the 6-month follow-up. In the risk assessment, the septalE/(E′×S′)can be evaluated together with the conventional echocardiographic techniques.

Abstract P300: Cardiac Ly6C high Monocyte Accumulation and Remodeling Depend on the Mineralocorticoid Receptor in Endothelial Cells

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Achim Lother ◽  
Aurelia Hübner ◽  
Ingo Hilgendorf ◽  
Tilman Schnick ◽  
Martin Moser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diastolic Dysfunction ◽  
Mineralocorticoid Receptor ◽  
Cardiac Fibrosis ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Marker Gene ◽  
Pressure Overload ◽  
Left Ventricular

Introduction: Inflammation is a key driver for the development of cardiac fibrosis and diastolic dysfunction. Aldosterone promotes the expression of adhesion molecules and vascular inflammation. Thus, the goal of the present study was to examine the significance of endothelial MR for pressure overload induced cardiac inflammation and remodeling. Methods and results: Mice with endothelial cell-specific deletion of the mineralocorticoid receptor (MR Cdh5Cre ) were generated using the Cre/loxP system. MR Cdh5Cre and Cre-negative littermates (MR wildtype ) underwent transverse aortic constriction (TAC, n=5-7 per group). After two weeks of pressure overload echocardiography revealed diastolic dysfunction in MR wildtype (mitral valve E acceleration time TAC 15.7 ± 0.5 vs. sham 12.8 ± 0.4 ms, P<0.05) but not in MR Cdh5Cre mice (TAC 11.2 ± 0.6 vs. sham 12.2 ± 0.9 ms, n.s.). Cardiac hypertrophy (ventricle weight 143.2 ± 5.2 vs. MR wildtype 167.3 ± 6.7 mg, P<0.001) and interstitial fibrosis (sirius red stained area 8.2 ± 4.7 vs. MR wildtype 13.5 ± 4.5 %, P<0.05) following TAC were attenuated in MR Cdh5Cre mice. mRNA expression of atrial natriuretic peptide ( Nppa , 2429 ± 1230 vs. MR wildtype 7051 ± 3182 copies/10 4 copies Rps29 , P<0.01) or the fibrosis marker gene collagen 1a1 ( Col1a1 , 256 ± 89 vs. MR wildtype 432 ± 165 copies/10 4 copies Rps29 , P<0.05) as determined by qRT-PCR confirmed these findings. Cardiac leukocytes were quantitatively analyzed by fluorescence assisted cell sorting using specific antibodies. Numbers of CD45 + leukocytes were similarly increased after TAC in the hearts of both genotypes (MR Cdh5Cre 3840 ± 443 vs. MR wildtype 4051 ± 385 /mg tissue, n.s.). Subtype analysis revealed a shift towards CD45 + CD11b + F4/80 low Ly6C high monocytes vs. CD45 + CD11b + F4/80 high Ly6C low macrophages in the heart of MR wildtype (TAC 20 ± 6 vs. sham 4 ± 1 % of CD45 + CD11b + , P<0.05) but not of MR Cdh5Cre mice (TAC 6 ± 2 vs. sham 3 ± 1 % of CD45 + CD11b + , n.s.). Conclusion: MR deletion from endothelial cells ameliorates left ventricular remodeling and diastolic dysfunction after pressure overload. The protective effect of endothelial MR deletion is associated with a shift towards less pro-inflammatory Ly6C high monocytes and more reparative Ly6C low macrophages.

scholarly journals P1572 The role of 3D echocardiography in the evaluation of left ventricular remodeling

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
O Guseva ◽  
O Guseva ◽  
O Mamaeva ◽  
N Pavlova ◽  
D Pavlov ◽  
...  
Keyword(s):  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Black Blood ◽  
Lv Mass ◽  
Lv Remodeling ◽  
3D Echo ◽  
Group A ◽  
High Dynamic ◽  
Group B

Abstract Purpose to assess the left ventricular (LV) remodeling with using transthoracic 3D Echo and MRI in young athletes. Materials for the period from October 2015 to April 2018, 88 athletes (61 men and 27 women) were examined. Mean age was 20.8 ± 3.9 years. Group A (professionals) – 65 athletes (4 or more training days a week, experience in sports for at least 7 years, the presence of at least the 1st sports category). Group B (Amateurs) – 23 athletes (3 or less training days a week). By types of loads were identified 4 groups: 1st - high-static, low-dynamic (climbing); 2nd - medium-static, medium-dynamic (volleyball, Rugby, sports dancing); 3rd - medium-static, high-dynamic (badminton, orienteering, hockey); 4th - high-static, high-dynamic (triathlon, water polo, rowing). Methods 2D-, 3D-Echo was performed on Vivid E9 XDclear 4D (GE, USA). With the help of software package for processing 3D arrays (4D auto LVQ and 4D Strain and LV-mass) in automatic and semi-automatic mode was obtained end diastolic and end systolic volumes (EDV, ESV), ejection fraction (EF) and LV mass. The device was used for MRI - Avanto (Siemens) - 1.5 T, using: sensors for breathing and synchronization with ECG, standard surface coil Body Matrix. Visualization of the mobile myocardium was carried out by SSFP protocols in standard two-and four-chamber view, as well as on the short axis. In addition, the black-blood Protocol was performed in axial projection for visualization of mediastinal organs and chest. Evaluation of the results was performed on a workstation Syngo Via VB10B (Siemens) using a worker thread MR Cardiac analisis. Results There were significant differences in the types of loads (p &lt; 0.001): 22% of men in Group B had 1st type, 2nd type - 78% of men and 93% of women in group B, 3rd type - 45% of men and 36% of women in group A, 4th type - 39% of men and 21% of women in group A. In the evaluation of LV remodeling and its relationship with the type of loads revealed significant differences (p &lt; 0.01): 87.5% had LV remodeling (95.4% - aggregate type load 1, 2, 3), 6.8% - concentric remodeling (21.7% of all type 4), and 4.5% eccentric hypertrophy (8.7% of all type 4), 1.1 per cent of concentric hypertrophy (4.4% of all type 4). Consequently, most athletes with loads of type 4 had different types of LV remodeling. Comparing 3D Echo and MRI, high-grade positive correlations were obtained in indicators: EDV (R 0.82, p &lt; 0.0001), ESV (R 0.80, p &lt; 0.0001), LV mass (R 0.85, p &lt; 0.0001), as well as moderate positive the index of EDV (R 0.54, p &lt; 0.037) and unreliable for the EF. Conclusions three-dimensional visualization allows to carry out a reliable assessment of the volumetric parameters of the heart chambers, comparable with MRI data and to identify the signs and type of LV remodeling. Requires further study of the performance of 3D Echo in athletes, given the lack of normative data on the modern stage.

Sign in / Sign up

Export Citation Format

Share Document