Patrick S. Wolf, MD, Heather E. Merry, MD, Alexander S

Slides:

Advertisements

Similar presentations

Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion Babu V Naidu, FRCS, Steven M Woolley, MRCS, Alexander S Farivar,

Advertisements

Aprotinin improves kidney function and decreases tubular cell apoptosis and proapoptotic signaling after renal ischemia-reperfusion Ajay Kher, MD, Kirstan.

Prevention of lung ischemia–reperfusion injury by short hairpin RNA–mediated caspase- 3 gene silencing Yong-Xing Zhang, MD, Hong Fan, PhD, Yu Shi, MD,

Prevention of ischemia-reperfusion injury in cardiac surgery: Therapeutic strategies targeting signaling pathways Kay Maeda, MD, PhD, Marc Ruel, MD,

Activation of mitogen-activated protein kinases during preparation of vein grafts and modulation by a synthetic inhibitor Costas Bizekis, MD, Giuseppe.

Role of Toll-Like Receptor-4 in Lung Ischemia-Reperfusion Injury

Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats

Dextran sulfate modulates MAP kinase signaling and reduces endothelial injury in a rat aortic clamping model Yara Banz, MD, PhD, Thusitha Gajanayake,

Functional Roles of Tumor Necrosis Factor-Alpha and Interleukin 1-Beta in Hypoxia and Reoxygenation Heather E. Merry, MD, Patrick Phelan, MD, Matthew.

Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion Babu V Naidu, FRCS, Steven M Woolley, MRCS, Alexander S Farivar,

Is hyperglycemia bad for the heart during acute ischemia?

Yong An, MD, Ying-Bin Xiao, MD

Baiya Krishnadasan, MD, Babu V

Lung injury after simulated cardiopulmonary bypass in an isolated perfused rat lung preparation: Role of mitogen-activated protein kinase/Akt signaling.

Patrick Phelan, MD, Heather E

Philip A. Rascoe, MD, Xiaobo Cao, MD, Jonathan C. Daniel, MD, Steven D

Toll-Like Receptor 4 Mediates Lung Ischemia-Reperfusion Injury

Chadrick E. Denlinger, MD

Interleukin-6 Regulation of Direct Lung Ischemia Reperfusion Injury

Nebulized nitrite protects rat lung grafts from ischemia reperfusion injury Toshihiro Okamoto, MD, PhD, Xiaoying Tang, MS, Allison Janocha, BS, Caral.

JNK mediates hepatic ischemia reperfusion injury

How should we treat air leaks?

Go on-pump or off-pump in diabetic patients?

Single-dose rosuvastatin ameliorates lung ischemia–reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage.

Intramyocardial injection of tannic acid attenuates postinfarction remodeling: A novel approach to stabilize the breaking extracellular matrix Hao Zhang,

Lung cancer cell invasion and expression of intercellular adhesion molecule-1 (ICAM-1) are attenuated by secretory phospholipase A2 inhibition Jessica.

Erythropoietin activates the phosporylated cAMP [adenosine 3′5′ cyclic monophosphate] response element-binding protein pathway and attenuates delayed.

Oral pretreatment with a green tea polyphenol for cardioprotection against ischemia– reperfusion injury in an isolated rat heart model Shigeki Yanagi,

Conduit conundrum: If not two, why three?

Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus B. Krishnadasan, MD, B. Naidu, MBBS,

Volume 120, Issue 2, Pages (February 2001)

Atorvastatin increases oxidative stress and modulates angiogenesis in Ossabaw swine with the metabolic syndrome Nassrene Y. Elmadhun, MD, Antonio D.

Endotracheal calcineurin inhibition ameliorates injury in an experimental model of lung ischemia-reperfusion Steven M. Woolley, MRCS, Alexander S. Farivar,

It's not “just a shunt” but sometimes it should be…

Differential effects on the mesenteric microcirculatory response to vasopressin and phenylephrine after cardiopulmonary bypass Tanveer A. Khan, MD, Cesario.

A first start for lung transplantation?

Ashok Muniappan, MD The Journal of Thoracic and Cardiovascular Surgery

Xianyao Xu, MS, Jennifer L. Philip, MD, Md

Inhibition of nuclear factor κB by IκB superrepressor gene transfer ameliorates ischemia-reperfusion injury after experimental lung transplantation Takaaki.

Validating the use of short interfering RNA as a novel technique for cell-specific target gene knockdown in lung ischemia–reperfusion injury Heather.

Inhibition of the transcriptional activator protein nuclear factor κb prevents hemodynamic instability associated with the whole-body inflammatory response.

Joseph A. Dearani, MD, Michael J. Ackerman, MD, PhD

Importance of endothelial nitric oxide synthase for the hypothermic protection of lungs against ischemia-reperfusion injury Li Zhang, MD, Sanjeev Kumar,

Resection of primary lung cancer with incidental pleural seeding: Seeds of change or reap what you sow? Jules Lin, MD The Journal of Thoracic and Cardiovascular.

Daniel T. Engelman, MD, FACS, Michael J. Germain, MD

Fueling the heart: Shifting the myocardial metabolome by targeting endothelial autophagy Nicholas D. Andersen, MD The Journal of Thoracic and Cardiovascular.

A fate worse than death Jennifer S. Lawton, MD

Uma M. Sachdeva, MD, PhD, Daniela Molena, MD

The Ross procedure: Time to reevaluate the guidelines

Passing the torch The Journal of Thoracic and Cardiovascular Surgery

Patrick T. Roughneen, MD, Grant T. Fankhauser, MD, Abe DeAnda, MD

β-chemokine function in experimental lung ischemia-reperfusion injury

Jason J. Han, MD, Pavan Atluri, MD

Inhibitory kappa B kinase-β is a target for specific nuclear factor kappa B-mediated delayed cardioprotection Nancy C. Moss, MD, Ru-Hang Tang, PhD, Monte.

The Journal of Thoracic and Cardiovascular Surgery

Discussion The Journal of Thoracic and Cardiovascular Surgery

The future of cardiac surgery training: A survival guide

“The more things change…”: The challenges ahead

Commentary: Judgment day: Should you add atrial fibrillation ablation?

Toward a more rational approach in treating type B aortic dissection

Toll-like receptor 4 inhibition attenuates ischemia-reperfusion injury in rats: Will it work in human beings? Chadrick E. Denlinger, MD The Journal.

Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury Alexander S Farivar, MD, Baiya Krishnadasan, MD, Babu.

Ryan R. Davies, MD The Journal of Thoracic and Cardiovascular Surgery

Respect the aorta The Journal of Thoracic and Cardiovascular Surgery

Proactive or reactive? Best approach to limb ischemia in peripheral venoarterial extracorporeal life support Matthew C. Black, MD, Mark S. Slaughter,

Of mice and men… The Journal of Thoracic and Cardiovascular Surgery

Did you like Terminator 3 better than Terminator 2

Samuel Kim, MD The Journal of Thoracic and Cardiovascular Surgery

Edward Y. Chan, MD, Michael J. Reardon, MD

Calpain inhibitors: The aspirin of the 21st century?

Presentation transcript:

Stress-activated protein kinase inhibition to ameliorate lung ischemia reperfusion injury Patrick S. Wolf, MD, Heather E. Merry, MD, Alexander S. Farivar, MD, Anton S. McCourtie, MD, Michael S. Mulligan, MD The Journal of Thoracic and Cardiovascular Surgery Volume 135, Issue 3, Pages 656-665 (March 2008) DOI: 10.1016/j.jtcvs.2007.11.026 Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Electromobility shift assay for activator protein 1. Vehicle-treated positive control animals (phosphate-buffered saline solution lane 3, phosphate-buffered saline solution plus dimethylsulfoxide lane 4) exhibited marked activator protein 1 nuclear translocation relative to negative control animals (lane 2). Activator protein 1 translocation was decreased significantly with p38 inhibition (lanes 5 and 6, p = .03) and c-jun N-terminal kinase inhibition (lanes 7 and 8, p = .008). Cold competition lane (lane 1) verified band as activator protein 1. The Journal of Thoracic and Cardiovascular Surgery 2008 135, 656-665DOI: (10.1016/j.jtcvs.2007.11.026) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Western blots for phosphorylated p38 (p-p38), c-jun N-terminal kinase (pJNK), and extracellular signal–regulated kinase (pERK1/2) demonstrating inhibitor specificity. Target mitogen-activated protein kinases for each inhibitor are indicated with heavy outlines. Specific p38, c-jun N-terminal kinase, and extracellular signal–regulated kinase inhibitions were achieved with FR167653 (FR, 6 mg/kg), SP600125 (SP, 25 mg/kg), and U0126 (U0, 200 μg/kg), respectively, after 90 minutes of ischemia and 15 minutes of reperfusion (IR 15). The Journal of Thoracic and Cardiovascular Surgery 2008 135, 656-665DOI: (10.1016/j.jtcvs.2007.11.026) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Immunohistochemical staining for phosphorylated p38 (A), c-jun N-terminal kinase (B), and extracellular signal–regulated kinase (C). Left column represents lung sections from unmanipulated negative control animals, with no staining for any phosphorylated mitogen-activated protein kinase isoforms. Right column represents lung sections from positive control animals subjected to 90 minutes of ischemia followed by 15 minutes of reperfusion (IR 15). Phosphorylated p38 and c-jun N-terminal kinase localized exclusively to alveolar macrophages (thin arrows). Phosphorylated extracellular signal–regulated kinase localized to endothelial (thick outline arrow) and epithelial cells (thick dark arrow). The Journal of Thoracic and Cardiovascular Surgery 2008 135, 656-665DOI: (10.1016/j.jtcvs.2007.11.026) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Electromobility shift assay for nuclear factor κB. Unmanipulated negative control animals demonstrated minimal nuclear translocation (lane 2). After 90 minutes of ischemia and 15 minutes of reperfusion, vehicle treated-positive control animals (with phosphate buffered saline solution lane 3, with phosphate-buffered saline solution plus dimethylsulfoxide lane 4) demonstrated marked translocation of nuclear factor κB. FR167653 (lanes 5 and 6) and SP600125 (lanes 7 and 8) significantly reduced transactivation of nuclear factor κB relative to that in positive control animals (FR167653 P = .02, SP600125 P = .007). Cold competition lane (lane 1) verified band as nuclear factor κB. The Journal of Thoracic and Cardiovascular Surgery 2008 135, 656-665DOI: (10.1016/j.jtcvs.2007.11.026) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Western blots for phosphorylated p38 (A), c-jun N-terminal kinase (B), and extracellular signal–regulated kinase (C). Positive control animals (phosphate-buffered saline solution in lane 2, phosphate-buffered saline solution plus dimethylsulfoxide in lane 3) exhibited significantly more mitogen-activated protein kinase phosphorylation than did unmanipulated negative control animals (lane 1, p38 P = .04, c-jun N-terminal kinase P = .04, extracellular signal–regulated kinase P = .01). FR167653-treated animals (lane 4) demonstrated significantly reduced p38 phosphorylation relative to positive control animals (P = .03), wheras c-jun N-terminal kinase and extracellular signal–regulated kinase phosphorylation were unaffected. SP600125 treatment (lane 5) inhibited c-jun N-terminal kinase phosphorylation (P = .04) and did not significantly reduce extracellular signal–regulated kinase or p38 phosphorylation. Relative to positive control animals, UO126-treated animals (lane 6) showed reduced extracellular signal–regulated kinase phosphorylation (P = .03) but no significant inhibition of either p38 or c-jun N-terminal kinase. The Journal of Thoracic and Cardiovascular Surgery 2008 135, 656-665DOI: (10.1016/j.jtcvs.2007.11.026) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions