scholarly journals Development of a preclinical model of ischemic cardiomyopathy in swine

2011 ◽  
Vol 301 (2) ◽  
pp. H530-H537 ◽  
Author(s):  
Kiyotake Ishikawa ◽  
Dennis Ladage ◽  
Yoshiaki Takewa ◽  
Elisa Yaniz ◽  
Jiqiu Chen ◽  
...  
Keyword(s):  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Left Ventricular Ejection ◽  
Hibernating Myocardium ◽  
Left Ventricular Volumes ◽  
Preclinical Model ◽  
Large Animal ◽  
Total Occlusion ◽  
Ventricular Ejection Fraction

A number of promising therapies for ischemic cardiomyopathy are emerging, and the role of translational research in testing the efficacy and safety of these agents in relevant clinical models has become important. The goal of this study was to develop a chronic model of ischemic cardiomyopathy in a large animal model. In this study, 40 consecutive pigs were initially enrolled. To induce progressive stenosis, a plastic occluder with a fixed diameter of 1.0 mm fitted with an 18-gauge copper wire was placed around the proximal left anterior descending (LAD) coronary artery. Coronary angiography, hemodynamic measurements, and echocardiography were performed at 2 wk and 1, 2, and 3 mo. Overall mortality was 26% at 3 mo, and up to 80% of the pigs showed total occlusion of LAD at 1 mo. A significant depression of peak LV pressure rate of rise (+dP/d tmax) was observed in the animals showing total artery occlusion throughout the study. Left ventricular ejection fraction was also impaired, and the left ventricular volumes tended to be larger in the pigs with occlusion. Approximately 10% of scar tissue was found in the LAD occluded pigs, whereas the coronary flow pattern in the rest of the area took the pattern of hibernating myocardium. At the same time, histological and protein analysis established the presence of fibrosis and ongoing apoptosis in the ischemic area. In this model, the timing and incidence of total occlusion and low mortality offer significant advantages over other ischemic cardiomyopathy models in conducting preclinical studies.

scholarly journals Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity

2020 ◽  
Author(s):  
Carlos Galán-Arriola ◽  
Rocio Villena-Gutiérrez ◽  
María I Higuero-Verdejo ◽  
Iván A Díaz-Rengifo ◽  
Gonzalo Pizarro ◽  
...  
Keyword(s):  
Contractile Function ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Left Ventricular Ejection ◽  
Large Animal ◽  
Ischaemic Preconditioning ◽  
Mitochondrial Fragmentation ◽  
Ventricular Ejection Fraction ◽  
Remote Ischaemic Preconditioning

Abstract Aims Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and results Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. Conclusion In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.

scholarly journals Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gen Suzuki ◽  
Rebeccah F. Young ◽  
Merced M. Leiker ◽  
Takayuki Suzuki
Keyword(s):  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Large Animal ◽  
Nuclear Density ◽  
Ventricular Ejection Fraction ◽  
Coronary Microembolization ◽  
Lv Dysfunction ◽  
Cell Based Therapy

A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n=11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106,n=5) or saline (untreated,n=6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure.

scholarly journals Transcatheter closure of ventricular septal rupture with prolonged support of intra-aortic balloon pump after primary PCI: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuan Yang ◽  
Yong Sun ◽  
Deling Zou ◽  
Zhaoqing Sun ◽  
Xinzhong Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Transcatheter Closure ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Drug Eluting Stent ◽  
Ventricular Septal Rupture ◽  
Total Occlusion ◽  
Ventricular Ejection Fraction ◽  
Intra Aortic Balloon Pump

Abstract Background Ventricular septal rupture (VSR) is a rare but severe complication of acute myocardial infarction (AMI). For such cases, surgical repair is recommended by major guidelines, but not always possible for such cases. Case presentation A 72-year-old man presented to the emergency room. ECG showed the ST-segment was elevated by 2–3 mm in lead II, III, and aVF, with Q-waves. Coronary angiography (CAG) showed multi-vessel disease with a total occlusion of the right coronary artery (RCA) and severe stenosis of the left anterior descending artery (LAD). A diagnosis of acute inferior myocardial infarction was made. VSR occurred immediately after percutaneous coronary intervention (a 2.5 × 20 mm drug-eluting stent implanted in RCA), and the patient developed cardiogenic shock. An intra-aortic balloon pump (IABP) was used to stabilize the hemodynamics. Transthoracic echocardiography (TTE) revealed an 11.4-mm left-to-right shunt in the interventricular septum. An attempt was made to reduce the IABP augmentation ratio for weaning on day 12 but failed. Transcatheter closure was conducted using a 24-mm double-umbrella occluder on day 28. The patient was weaned from IABP on day 31 and underwent secondary PCI for LAD lesions on day 35. The patient was discharged on day 41. Upon the last follow-up 6 years later, CAG and TTE revealed no in-stent restenosis, no left-to-right shunt, and 51% left ventricular ejection fraction. Conclusions Prolonged implementation of IABP can be a viable option to allow deferred closure of VSR in AMI patients, and transcatheter closure may be considered as a second choice for the selected senior and vulnerable patients, but the risk is still high.

scholarly journals Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy

2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Tachyarrhythmias ◽  
Ventricular Ejection Fraction ◽  
One Year ◽  
The Impact

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.

scholarly journals Indicators of the left ventricular-arterial coupling interaction in chronic forms of ischemic heart disease: relationships of the protradenomedullin and N-terminal probrain natriuretic peptide

Kardiologiia ◽  
2019 ◽  
Vol 59 (6S) ◽  
pp. 41-50
Author(s):  
E. I. Myasoedova ◽  
L. P. Voronina ◽  
O. S. Polunina ◽  
Yu. G. Shvarts
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Coupling Interaction ◽  
Left Ventricular Arterial Coupling

Purpose of the study. Analyze the parameters of the interaction between the left ventricle and the arterial system in patients with chronic forms of coronary heart disease and to identify relationships with levels of proadrenomedullin (MR‑proADM) and N‑terminal precursor of the brain natriuretic peptide B (NT‑proBNP).Materials and methods.240 patients with chronic forms of coronary heart disease (median – 55,9 [43; 63] years) and Q‑forming myocardial infarction in the past were examined. Of these, 110 patients with myocardial infarction and preserved lef ventricular ejection fraction and 130 patients with ischemic cardiomyopathy. All patients were calculated parameters of lef ventricular‑arterial interaction and the determination in blood serum levels of MR‑proADM and NT‑proBNP.Results.In patients with ischemic cardiomyopathy, an increase in the lef ventricular‑arterial interaction index was detected (2,51 [1,18; 5,00]), which reflects a decrease in the functional abilities and efficiency of the heart. In patients with myocardial infarction and a preserved left ventricular ejection fraction, this indicator was in the range of normal values (0,78 [0,55; 1,07]), which indicates an effective cardiac work. A study of MR‑proADM and NT‑proBNP levels demonstrated an increase in both groups (1,72 [1,56; 1,98] nmol/l and 779,3 [473; 2193] pg/ml in the group of patients with ischemic cardiomyopathy; 0,89 [0,51; 1,35] nmol/l and 246 [118; 430] pg/ml in the group of patients with myocardial infarction and preserved left ventricular ejection fraction), and the correlation analysis with left ventricular‑arterial coupling interaction parameters allowed identify statistically significant connections (in the group of patients with ischemic cardiomyopathy: with the level of MR‑proADM ‑ r=0,67, p=0,006, with the level of NT‑proBNP ‑ r=0,78, p<0,001; in the group of patients with myocardial infarction and preserved left ventricular ejection fraction: with MR‑proADM level ‑ r=‑0,52, p=0,024, with NT‑proBNP level ‑ r =‑0,38, p=0,037).Conclusion.The findings suggest a pathogenetic association between the biomarkers under study and the parameters of left ventricular‑arterial coupling interaction.

P1964Impact of successful coronary intervention for chronic total occlusion on long-term clinical outcome of patients with impaired and preserved left ventricular ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Tanaka ◽  
T Tada ◽  
Y Fuku ◽  
T Goto ◽  
K Kadota
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Chronic Total Occlusion ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Total Occlusion ◽  
Ventricular Ejection Fraction ◽  
Percutaneous Coronary ◽  
Procedural Success

Abstract Background Successful recanalisation of percutaneous coronary intervention for chronic total occlusion lesions has been associated with improved survival. Purpose This study aimed to assess the impact of successful percutaneous coronary intervention for chronic total occlusion lesions on the long-term outcome of patients with impaired and preserved left ventricular ejection fraction (LVEF). Methods The study sample consisted of 842 consecutive patients (928 chronic total occlusion lesions) undergoing percutaneous coronary intervention at our institution between October 2005 and December 2009. We divided them into 3 groups by the degree of LVEF: less than 40% (severely reduced LVEF, n=140), 40% to 59% (moderately reduced LVEF, n=470), and 60% and above (normal LVEF, n=232). We evaluated mortality during the 10-year follow-up period the basis of procedural success and failure. Results The overall procedural success rate was 89.1%. Median follow-up duration was 7.9 years. The 10-year cumulative incidences of cardiac death in each degree of LVEF are shown in the Figure. Conclusions Successful recanalisation for chronic total occlusion lesions in patients with impaired LVEF may be associated with reduced cardiac mortality.

P4525Differential effect of CRT in ischemic and non-ischemic cardiomyopathy: longterm follow-up data from a single center cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P C Kahr ◽  
P Kaufmann ◽  
J Kuster ◽  
J Tonko ◽  
A Breitenstein ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Male Gender ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Study Endpoint ◽  
Ventricular Ejection Fraction

Abstract Background Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in selected symptomatic patients with reduced left ventricular ejection fraction (LVEF) and wide QRS complex. However, some patients fail to benefit from CRT. Data on the differential role of baseline and follow-up left ventricular ejection fraction (LVEF) on outcome in patients with ischemic compared to non-ischemic cardiomyopathy (ICM, N-ICM) is controversial. Purpose To test, whether ICM and N-ICM patients differ in outcome after CRT during long-term follow-up and whether predictors for survival after CRT differ between the two groups. Methods All patients undergoing CRT implantation at our institution between November 2000 and January 2015 were evaluated (n=418). All ICM/N-ICM patients with follow-up echocardiography within 1 year after CRT implantation (FU1) and a second echocardiography >1 year after FU1 (FU2) were included in the analysis (n=253). Primary post-hoc defined study endpoint was the composite of all-cause death, heart transplantation or implantation of a ventricular assist device. Results Compared to patients with N-ICM (n=160, median age 64 years [IQR 54–71], 71% male), ICM patients (n=93, median age 70 years [IQR 61–75], 84% male) were significantly older and had a higher prevalence of male gender, concomitant diabetes mellitus and arterial hypertension. There were no significant differences in pre-implantation echocardiographic features (LVEF, LVEDV, RV-FAC, severity of mitral regurgitation), QRS width and NT-proBNP levels between the groups. However, the hazard for reaching the primary endpoint was significantly higher in patients with ICM compared to N-ICM both on univariate analysis (HR 1.62 [95% CI 1.09–2.42], p=0.018) and after multivariate correction (aHR 2.13 [1.24–3.66], p=0.006). While higher NT-proBNP levels and greater right ventricular fractional area change were positively correlated with the hazard of death in both ICM and N-ICM (see Figure), lower LVEF at baseline was associated with an increased risk of death only in ICM but not in N-ICM (HR 0.95 [0.91–0.99], p=0.029 vs. HR 1.00 [0.96–1.04], p=0.945). Male gender, lower BMI and NYHA class ≥ III were positively correlated with the endpoint in N-ICM, but not in ICM. Importantly, LVEF at FU1 (median 4.7 months after implantation) and FU2 (median 47.1 months after implantation) were found to correlate signficantly with the endpoint in both ICM and N-ICM. Conclusion Our findings highlight important differences in ischemic and non-ischemic patient populations undergoing CRT. While overall survival of patients with N-ICM exceeds survival in ICM, several other factors (including LVEF) have differential effects on response to CRT in these two patient groups.

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