Glucocorticoids Alter the Balance Between Pro- and Anti-inflammatory Mediators in the Myocardium in a Porcine Model of Brain Death

McLean, Karen; Duffy, Jodie Y.; Pandalai, Prakash K.; Lyons, Jefferson M.; Bulcao, Christian F.; Wagner, Connie J.; Akhter, Shahab A.; Pearl, Jeffrey M.

doi:10.1016/j.healun.2006.10.011

Cited by 34 publications

(32 citation statements)

References 61 publications

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“…The mechanisms by which glucocorticoids preserve myocardial function, however, do not appear to involve the NF-B pathway. 21,22 This indicates that the cardiac protection mechanism after brain death could either be NF-B dependent or NF-B independent.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the Protective Effects of N-acetylcysteine on the Heart of Brain-Dead Ba-Ma Miniature Pigs

Zhai

Feng

Huo

et al. 2009

The Journal of Heart and Lung Transplantation

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Section: Discussionmentioning

confidence: 99%

Mechanism of the Protective Effects of N-acetylcysteine on the Heart of Brain-Dead Ba-Ma Miniature Pigs

Zhai

Feng

Huo

et al. 2009

The Journal of Heart and Lung Transplantation

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“…51 Nonetheless, they have been shown to improve oxygenation, reduce extravascular lung water, increase lung yield, and reduce inflammation in the liver, heart, and kidney. 45,51,53,54 Available evidence recommends a methylprednisolone IVB, which may be repeated every 12 to 24 hours depending on the time between initial determination of brain death and the point of organ recovery.…”

Section: Corticosteroid Monotherapymentioning

confidence: 99%

The Role of Hormone Replacement Therapy in the Intensive Care Management of Deceased Organ Donors

Smetana

Kimmons

Jones³

2015

Critical Care Nursing Quarterly

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Donation after brain death remains the primary contributor to the supply of organs available for transplantation in the United States. After brain death, both a surge of catecholamines and a dysregulation of the neurohormonal axis may result in hypotension, decreased organ perfusion, and reduced viability of organs to be transplanted. Hormone replacement therapy is widely used to maintain organ perfusion and has been shown to increase the number of organs procured. This article reviews the literature and mechanisms supporting the use of hormone replacement therapy in brain-dead organ donors and provides clinicians with information regarding the administration, monitoring, and preparation of thyroid hormone, arginine vasopressin, and corticosteroids.

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“…Their protective effect is likely based on a general mechanism independent of cell type. Furthermore, active molecules found in our 3-h assay included ion channel blockers and cell surface receptors that were previously shown to ameliorate cell injury in oxidative stress in cultured cells (in many cases cardiomyocytes) in vitro or in various models of myocardial infarction and injury in vivo (4,6,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). The effects of some of these compounds can be, again, linked to the PARP pathway, as minocycline has recently been identified as a fairly potent competitive PARP inhibitor (19,20), and the protective effect of certain calcium modulators may also be linked to an early calcium-dependent step in the cellular activation of PARP (18).…”

Section: Parp Activation Plays a Central Role In Oxidative Stressmentioning

confidence: 99%

Oxidant-induced cardiomyocyte injury: Identification of the cytoprotective effect of a dopamine 1 receptor agonist using a cell-based high-throughput assay

Gerö¹,

Módis²,

Nagy³

et al. 2007

Int J Mol Med

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Abstract. Myocyte injury due to myocardial reperfusion injury plays a crucial role in the pathogenesis of acute myocardial infarction even after successful coronary revascularization. Identification of compounds that reduce reperfusionassociated myocyte death is important. Therefore, we developed an in vitro model of myocardial reperfusion injury in H9c2 rat cardiomyocytes and applied a cell-based high-throughput approach to screen a standard library of pharmacologically active compounds (LOPAC) in order to identify drugs with cardioprotective effects. Oxidative stress was induced with hydrogen peroxide (H 2 O 2 ) treatment, which resulted in ~50% reduction in cell viability. Test compounds were added at a 3-μM final concentration as a pretreatment or in a delayed fashion (30 min after the peroxide challenge in order to imitate pharmacological treatment following angioplasty). Cells were cultured for 3 or 24 h. Viability was quantitated with the methylthiazolyldiphenyl-tetrazolium bromide method. Cytotoxicity and cytoprotection were also evaluated by measuring the lactate dehydrogenase activity in the cell culture supernatant. The screening identified a number of compounds with cytoprotective action, including molecules that are known to interfere with components of DNA repair and cell cycle progression, e.g. poly(ADP-ribose) polymerase (PARP) inhibitors, topoisomerase inhibitors, and cyclin dependent kinase inhibitors, or reduce energy consumption by interfering with cardiac myofilament function. A number of dopamine D1 receptor agonists also provided significant cytoprotection at 3 h, but only three of them showed a similar effect at 24 h: chloro-and bromo-APB and chloro-PB hydrobromide. Chloro-APB hydrobromide significantly reduced peroxide-induced PARP activation in the myocytes independently of its action on dopamine D1 receptors, but lacked PARP inhibitor capacity in a cell-free PARP assay system. In conclusion, the pattern of cytoprotective drugs identified in the current assay supports the overall validity of our model system. The findings demonstrate that cytoprotective agents, including novel indirect inhibitors of cellular PARP activation can be identified with the method, chloro-APB hydrobromide being one such compound. The current experimental setting can be employed for cell-based high-throughput screening of various compound libraries.

show abstract

Glucocorticoids Alter the Balance Between Pro- and Anti-inflammatory Mediators in the Myocardium in a Porcine Model of Brain Death

Cited by 34 publications

References 61 publications

Mechanism of the Protective Effects of N-acetylcysteine on the Heart of Brain-Dead Ba-Ma Miniature Pigs

Mechanism of the Protective Effects of N-acetylcysteine on the Heart of Brain-Dead Ba-Ma Miniature Pigs

The Role of Hormone Replacement Therapy in the Intensive Care Management of Deceased Organ Donors

Oxidant-induced cardiomyocyte injury: Identification of the cytoprotective effect of a dopamine 1 receptor agonist using a cell-based high-throughput assay

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