Epicardial infarct repair with basic fibroblast growth factor–enhanced CorMatrix-ECM biomaterial attenuates postischemic cardiac remodeling

Mewhort, H.E.; Turnbull, Jeffrey; Meijndert, H. Christopher; Ngu, Janet M.C.; Fedak, Paul W.M.

doi:10.1016/j.jtcvs.2013.08.005

Cited by 65 publications

(73 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, FGF-2 induces cardioprotection, 44 has a role as a chemotactic factor for stem cell homing after myocardial injury, 45 induces angiogenesis, 46,47 and improves remodeling after myocardial infarction in the rat. [48][49][50] The significance of the ticagrelorinduced attenuation and clopidogrel-induced normalization of the increase in FGF-2 levels 4 weeks after infarction is unclear. Although ticagrelor attenuated adverse remodeling after infarction, clopidogrel had no effect.…”

Section: Discussionmentioning

confidence: 99%

Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Ye¹,

Birnbaum

Perez‐Polo

et al. 2015

ATVB

108

111

View full text Add to dashboard Cite

Objective-In addition to P2Y 12 receptor antagonism, ticagrelor inhibits adenosine cell uptake. Prior data show that 7-day pretreatment with ticagrelor limits infarct size. We explored the acute effects of ticagrelor and clopidogrel on infarct size and potential long-term effects on heart function. Approach and Results-Rats underwent 30-minute ischemia per 24-hour reperfusion. (1) Ticagrelor (10 or 30 mg/kg) or clopidogrel (12.5 mg/kg) was given via intraperitoneal injection 5 minutes before reperfusion. (2) Rats received ticagrelor acute (intraperitoneal; 30 mg/kg), chronic (oral; 300 mg/kg per day) for 4 weeks starting 1 day after reperfusion or the combination (acute+chronic). Another group received clopidogrel (intraperitoneal [12.5 mg/kg]+oral [62.5 mg/kg per day]) for 4 weeks.(1) Ticagrelor dose-dependently reduced infarct size, 10 mg/kg (31.5%±1.8%; P<0.001) and 30 mg/ kg (21.4%±2.6%; P<0.001) versus control (45.3±1.7%), whereas clopidogrel had no effect (42.4%±2.6%). Ticagrelor, but not clopidogrel, increased myocardial adenosine levels, increased phosphorylation of Akt, endothelial NO synthase, and extracellular-signal-regulated kinase 1/2 4 hours after reperfusion and decreased apoptosis. (2) After 4 weeks, left ventricular ejection fraction was reduced in the vehicle-treated group (44.8%±3.5%) versus sham (77.6%±0.9%).All ticagrelor treatments improved left ventricular ejection fraction, acute (69.5%±1.6%), chronic (69.2%±1.0%), and acute+chronic (76.3%±1.2%), whereas clopidogrel had no effect (37.4%±3.7%). Ticagrelor, but not clopidogrel, attenuated fibrosis and decreased collagen-III mRNA levels 4 weeks after ischemia/reperfusion. Ticagrelor, but not clopidogrel, attenuated the increase in proinflammatory tumor necrosis factor-α, interleukin-1β, and interleukin-18, and increased anti-inflammatory 15-epi-lipoxin-A 4 levels. Conclusions-Ticagrelor, but not clopidogrel, administered just before reperfusion protects against reperfusion injury. This acute treatment or chronic ticagrelor for 4 weeks or their combination improved heart function, whereas clopidogrel, despite achieving a similar degree of platelet inhibition, had no effect. addition to platelet inhibition, ticagrelor, but not clopidogrel, has protective effects against ischemia-reperfusion that may help explain the differences in clinical benefit in the PLATO trial. 7,8 However, a recent multicenter, randomized, double-blind clinical trial did not show a clear clinical benefit in patients with STEMI receiving ticagrelor en route to the hospital versus in the catheterization laboratory. 16 As the study was not powered for benefit on cardiovascular events, it is inconclusive about the hypothesis that administration of ticagrelor after onset of ischemia (in contrast to pretreatment just before reperfusion) can ameliorate reperfusion injury. In addition, as the median time difference between the prehospital and the in-hospital ticagrelor administration groups was only 31 minutes, 16 it is plausible that ticagrelor absorption was insufficient an...

show abstract

Section: Discussionmentioning

confidence: 99%

Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Ye¹,

Birnbaum

Perez‐Polo

et al. 2015

ATVB

108

111

View full text Add to dashboard Cite

show abstract

“…Accordingly, this observation may suggest that therapies that prevent heart dilation (such as a ventricular constraint device (54)) might have a role in preventing this aspect of relapse. Most recently an FDA-approved biologic ECM construct synthesized from decellularized porcine small intestinal submucosa (CorMatrix Cardiovascular Inc. CA, USA) (55) that is rich in collagen, glycosaminoglycans and growth factors that stimulates ECM production and increases the myofibroblast and cardiomyocyte numbers (56, 57) has been studied in conjunction with LVAD support. Preliminary data suggests that this combination has the potential to enhance cardiac function and promote myocardial recovery (58).…”

Section: Enhancing Recovery: Impediments and Opportunitiesmentioning

confidence: 99%

Left ventricular assist device-induced reverse remodeling: it’s not just about myocardial recovery

Marinescu

Uriel

Mann

et al. 2016

Expert Review of Medical Devices

View full text Add to dashboard Cite

Introduction The abnormal structure, function and molecular makeup of dilated cardiomyopathic hearts can be partially normalized in patients supported by a left ventricular assist device (LVAD), a process called reverse remodeling. This leads to recovery of function in many patients, though the rate of full recovery is low and in many cases is temporary, leading to the concept of heart failure remission, rather than recovery. Areas covered We summarize data indicative of ventricular reverse remodeling, recovery and remission during LVAD support. These terms were used in searches performed in Pubmed. Duplication of topics covered in depth in prior review articles were avoided. Expert Commentary Although most patients undergoing mechanical circulatory support (MCS) show a significant degree of reverse remodeling, very few exhibit sufficiently improved function to justify device explantation, and many from whom LVADs have been explanted have relapsed back to the original heart failure phenotype. Future research has the potential to clarify the ideal combination of pharmacological, cell, gene, and mechanical therapies that would maximize recovery of function which has the potential to improve exercise tolerance of patients while on support, and to achieve a higher degree of myocardial recovery that is more likely to persist after device removal.

show abstract

“…At 16 wk of age, animals were euthanized, and hearts arrested in diastole and explanted. Passive pressure distention measures of the left ventricle (LV) were performed as previously described (18). In brief, a latex balloon connected to a closed fluid-filled system housing a pressure catheter was inserted into the LV, and volumes at 30 mmHg were recorded.…”

Section: Methodsmentioning

confidence: 99%

Tetrandrine reverses human cardiac myofibroblast activation and myocardial fibrosis

Teng

Svystonyuk

Mewhort

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

Epicardial infarct repair with basic fibroblast growth factor–enhanced CorMatrix-ECM biomaterial attenuates postischemic cardiac remodeling

Cited by 65 publications

References 35 publications

Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Left ventricular assist device-induced reverse remodeling: it’s not just about myocardial recovery

Tetrandrine reverses human cardiac myofibroblast activation and myocardial fibrosis

Contact Info

Product

Resources

About