Post-surgery echocardiography can predict the amount of ischemia-reperfusion injury and the resultant scar size

2020 ◽  
Author(s):  
Yijun Yang ◽  
Giana J Schena ◽  
Tao Wang ◽  
Steven R Houser
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mouse Heart ◽  
Murine Models ◽  
Ischemic Insult ◽  
Functional Changes ◽  
Post Surgery ◽  
Scar Size ◽  
Reparative Effect ◽  
Underlying Pathophysiology

In spite of advances in the diagnosis and treatment of ischemic heart disease (IHD), it remains the leading cause of death globally. Thus, there is an urgent demand to investigate the underlying pathophysiology and develop new therapies for the prevention and treatment of IHD. Murine models are widely used in IHD research because they are readily available, relatively inexpensive and can be genetically modified to explore mechanistic questions. Myocardial infarction in mice is induced by the blockage followed by reperfusion of the left anterior descending branch (LAD) to imitate human IHD diseases in clinics. This ischemia/reperfusion (I/R) model can be widely used to investigate the potential reparative effect of putative treatments. However, the surgical technique is demanding and can produce an inconsistent amount of damage, which can make identification of treatment effects challenging. Therefore, determining which hearts have been significantly damaged by I/R is an important consideration in studies designed to explore either the mechanisms of disrupted function or to test possible therapies. Noninvasive echocardiography (ECHO) is often used to determine structural and functional changes in the mouse heart following injury. In the present study, we determined that ECHO performed 3 days post-I/R surgery could predict the injury produced by the ischemic insult.

Rapamycin confers preconditioning-like protection against ischemia–reperfusion injury in isolated mouse heart and cardiomyocytes

2006 ◽  
Vol 41 (2) ◽  
pp. 256-264 ◽  
Author(s):  
Shakil A. Khan ◽  
Fadi Salloum ◽  
Anindita Das ◽  
Lei Xi ◽  
George W. Vetrovec ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mouse Heart

Abstract 103: Mechanistic Interplay Between Cardioprotection And Heart Regeneration Mediated By The ER-bound Transcription Factor Nrf1

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Miao Cui ◽  
Atmanli Ayhan ◽  
Ning Liu ◽  
Rhonda S Bassel-duby ◽  
Eric N Olson
Keyword(s):  
Transcription Factor ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Induced Pluripotent Stem Cell ◽  
Redox Balance ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Neonatal Cardiomyocytes ◽  
Underlying Mechanisms

Cardiomyocyte loss is the underlying basis for a majority of heart diseases. Preventing cardiomyocytes from death (cardioprotection) and replenishing the lost myocardium (regeneration) are the central goals for heart repair. Although cardioprotection and heart regeneration have been traditionally thought to involve separate mechanisms, protection of cardiomyocytes from injury or disease stimuli is a prerequisite to any meaningful regenerative response. In our study, we sought to understand how neonatal cardiomyocytes cope with injury-induced stress to regenerate damaged myocardium and whether the underlying mechanisms could be leveraged to promote heart regeneration and repair in adults. Using spatial transcriptomic profiling, we visualized regenerative cardiomyocytes reconstituting damaged myocardium after ischemia, and found that they are marked by expression of Nrf1, an ER-bound stress responsive transcription factor. Single-nucleus RNA sequencing revealed that genetic deletion of Nrf1 prevented neonatal cardiomyocytes from activating a transcriptional program required for heart regeneration. Conversely, overexpression of Nrf1 protected the adult mouse heart from ischemia/reperfusion injury. Nrf1 also protected human induced pluripotent stem cell-derived cardiomyocytes from cardiotoxicity induced by the chemotherapeutic drug doxorubicin. The cardioprotective function of Nrf1 is mediated by a dual stress response mechanism involving activation of the proteasome and maintenance of redox balance. Taken together, our study uncovers a unique adaptive mechanism activated in response to injury that maintains the tissue homeostatic balance required for heart regeneration. Reactivating these mechanisms in the adult heart represents a potential therapeutic approach for cardiac repair.

scholarly journals Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury

2015 ◽  
Vol 112 (17) ◽  
pp. E2253-E2262 ◽  
Author(s):  
Youn Wook Chung ◽  
Claudia Lagranha ◽  
Yong Chen ◽  
Junhui Sun ◽  
Guang Tong ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mouse Heart ◽  
Targeted Disruption

Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B−/− heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling. Compared with WT mitochondria, PDE3B−/− mitochondria were enriched in antiapoptotic Bcl-2, produced less reactive oxygen species, and more frequently contacted transverse tubules where PDE3B was localized with caveolin-3. Moreover, a PDE3B−/− mitochondrial fraction containing connexin-43 and caveolin-3 was more resistant to Ca2+-induced opening of the mitochondrial permeability transition pore. Proteomics analyses indicated that PDE3B−/− heart mitochondria fractions were enriched in buoyant ischemia-induced caveolin-3–enriched fractions (ICEFs) containing cardioprotective proteins. Accumulation of proteins into ICEFs was PKA dependent and was achieved by ischemic preconditioning or treatment of WT heart with the PDE3 inhibitor cilostamide. Taken together, these findings indicate that PDE3B deletion confers cardioprotective effects because of cAMP/PKA-induced preconditioning, which is associated with the accumulation of proteins with cardioprotective function in ICEFs. To our knowledge, our study is the first to define a role for PDE3B in cardioprotection against I/R injury and suggests PDE3B as a target for cardiovascular therapies.

scholarly journals Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARγ

2016 ◽  
Vol 311 (4) ◽  
pp. R676-R688 ◽  
Author(s):  
Ahmad Hanif ◽  
Matthew L. Edin ◽  
Darryl C. Zeldin ◽  
Christophe Morisseau ◽  
Mohammed A. Nayeem
Keyword(s):  
Epoxide Hydrolase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Hyperemia ◽  
Soluble Epoxide Hydrolase ◽  
Mouse Heart ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids (DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through modulation of oxylipin profiles, including an increase in EET/DHET ratio. Compared with sEH+/+, sEH−/− mice showed enhanced CRH, including greater repayment volume (RV; 28% higher, P < 0.001) and repayment/debt ratio (32% higher, P < 0.001). Oxylipins from the heart perfusates were analyzed by LC-MS/MS. The 14,15-EET/14,15-DHET ratio was 3.7-fold higher at baseline ( P < 0.001) and 5.6-fold higher post-ischemia ( P < 0.001) in sEH−/− compared with sEH+/+ mice. Likewise, the baseline 9,10- and 12,13-EpOME/DiHOME ratios were 3.2-fold ( P < 0.01) and 3.7-fold ( P < 0.001) higher, respectively in sEH−/− compared with sEH+/+ mice. 13-HODE was also significantly increased at baseline by 71% ( P < 0.01) in sEH−/− vs. sEH+/+ mice. Levels of 5-, 11-, 12-, and 15-hydroxyeicosatetraenoic acids were not significantly different between the two strains ( P > 0.05), but were decreased postischemia in both groups ( P = 0.02, P = 0.04, P = 0.05, P = 0.03, respectively). Modulation of CRH by peroxisome proliferator-activated receptor gamma (PPARγ) was demonstrated using a PPARγ-antagonist (T0070907), which reduced repayment volume by 25% in sEH+/+ ( P < 0.001) and 33% in sEH−/− mice ( P < 0.01), and a PPARγ-agonist (rosiglitazone), which increased repayment volume by 37% in both sEH+/+ ( P = 0.04) and sEH−/− mice ( P = 0.04). l-NAME attenuated CRH in both sEH−/− and sEH+/+. These data demonstrate that genetic deletion of sEH resulted in an altered oxylipin profile, which may have led to an enhanced CRH response.

Resident cardiac mast cells contribute to ischemia‐reperfusion injury in the isolated, perfused mouse heart

2008 ◽  
Vol 22 (S2) ◽  
pp. 47-47
Author(s):  
Tyler Habkirk Rork ◽  
Kori L Wallace ◽  
Dylan P Kennedy ◽  
Melissa A Marshall ◽  
Amy R Lankford ◽  
...  
Keyword(s):  
Mast Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mouse Heart

trans-Polydatin protects the mouse heart against ischemia/reperfusion injury via inhibition of the renin–angiotensin system (RAS) and Rho kinase (ROCK) activity

2017 ◽  
Vol 8 (6) ◽  
pp. 2309-2321 ◽  
Author(s):  
Dong Ming ◽  
Liao Songyan ◽  
Chen Yawen ◽  
Zheng Na ◽  
Ma Jing ◽  
...  
Keyword(s):  
Cardiac Disease ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Chinese Herb ◽  
Rho Kinase ◽  
Renin Angiotensin System ◽  
Mouse Heart ◽  
Polygonum Cuspidatum ◽  
Angiotensin System ◽  
Rock Activity

Background: Recent studies highlighted the protective benefits of a Chinese herb extract frompolygonum cuspidatum,trans-polydatin, on cardiac disease.

Metallothionein inhibits ischemia-reperfusion injury in mouse heart

1999 ◽  
Vol 276 (3) ◽  
pp. H993-H997 ◽  
Author(s):  
Y. James Kang ◽  
Guangqiu Li ◽  
Jack T. Saari
Keyword(s):  
Reperfusion Injury ◽  
Transgenic Mouse ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Transgenic Mouse Model ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Mouse Heart ◽  
Cardiac Protection ◽  
Heart Injury

Oxidative stress is believed to play a major role in ischemia-reperfusion injury to the heart. Metallothionein (MT), a potential free radical scavenger, may function in cardiac protection against ischemia-reperfusion damage. To test this hypothesis, a specific cardiac MT-overexpressing transgenic mouse model was used. The hearts isolated from these animals were subjected to 50 min of warm (37°C) zero-flow ischemia followed by 60- or 90-min reflow. Compared with the nontransgenic controls, the transgenic mouse hearts with MT concentrations ∼10-fold higher than normal showed significantly improved recovery of contractile force postischemia (69.2 ± 4.2 vs. 26.0 ± 6.0% at the end of 60-min reperfusion, P < 0.01). Efflux of creatine kinase from these transgenic hearts was reduced by more than 50% ( P < 0.01). In addition, the zone of infarction induced by ischemia-reperfusion at the end of 90-min reperfusion was suppressed by ∼40% ( P < 0.01) in the transgenic hearts. The results strongly indicate that MT provides protection against ischemia-reperfusion-induced heart injury.

scholarly journals Characterization of the sex-dependent myocardial S-nitrosothiol proteome

2016 ◽  
Vol 310 (4) ◽  
pp. H505-H515 ◽  
Author(s):  
Qin Shao ◽  
Jonathan Fallica ◽  
Kevin M. Casin ◽  
Elizabeth Murphy ◽  
Charles Steenbergen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Modification ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Premenopausal Women ◽  
Protein S ◽  
Female Group ◽  
Mouse Heart ◽  
Label Free ◽  
Cyclophilin D

Premenopausal women exhibit endogenous cardioprotective signaling mechanisms that are thought to result from the beneficial effects of estrogen, which we have shown to increase protein S-nitrosylation in the heart. S-nitrosylation is a labile protein modification that increases with a number of different forms of cardioprotection, including ischemic preconditioning. Herein, we sought to identify a potential role for protein S-nitrosylation in sex-dependent cardioprotection. We utilized a Langendorff-perfused mouse heart model of ischemia-reperfusion injury with male and female hearts, and S-nitrosylation-resin-assisted capture with liquid chromatography tandem mass spectrometry to identify S-nitrosylated proteins and modification sites. Consistent with previous studies, female hearts exhibited resilience to injury with a significant increase in functional recovery compared with male hearts. In a separate set of hearts, we identified a total of 177 S-nitrosylated proteins in female hearts at baseline compared with 109 S-nitrosylated proteins in male hearts. Unique S-nitrosylated proteins in the female group included the F1FO-ATPase and cyclophilin D. We also utilized label-free peptide analysis to quantify levels of common S-nitrosylated identifications and noted that the S-nitrosylation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a was nearly 70% lower in male hearts compared with female, with no difference in expression. Furthermore, we found a significant increase in endothelial nitric oxide synthase expression, phosphorylation, and total nitric oxide production in female hearts compared with males, likely accounting for the enhanced S-nitrosylation protein levels in female hearts. In conclusion, we identified a number of novel S-nitrosylated proteins in female hearts that are likely to contribute to sex-dependent cardioprotection.

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