Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function

Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function

The Brain-Dead Organ Donor

Addressing all aspects of brain death and thoroughly detailing how a potential organ donor should be maintained to ensure maximum use of the organs and cells, The Brain-Dead Organ Donor: Pathophysiology and Management is a landmark addition to the literature. This first-of-its-kind, multidisciplinary volume will be of interest to a large section of the medical community. The first section of the book reviews the historical, medical, legal, and ethical aspects of brain death. That is followed by two chapters on the pathophysiology of brain death as investigated in small and large animal models. This includes a review of the many hormonal changes, including the neuroendocrine- adrenergic ‘storm’, that takes place during and following the induction of brain death, and how they impact metabolism. The next section of the book reviews various effects of brain death, namely its impact on thyroid function, the inflammatory response that develops, and those relating to innate immunity. The chapters relating to assessment and management of potential organ donors will be of interest to a very large group of transplant surgeons and physicians as well as critical care and neurocritical care physicians and nurses. Neurologists, endocrinologists, neurosurgeons, and pathologists will also be interested, especially in the more basic science sections on various aspects of brain-death and hormonal therapy. Organ procurement organizations and transplant coordinators worldwide will also be interested in this title. Other chapters will be of interest to medical historians, medico-legal experts, and ethicists.CONTENIDO: Introduction, Dimitri Novitzky, David K. C. Cooper, Pages 1-6 -- Historical Aspects of the Diagnosis of Death, Félix Bacigalupo, Daniela A. Huerta Fernández, Pages 7-11 -- The Determination of Brain Death, Curtis M. Keller, Boris Chulpayev, Michael Hoffmann, Pages 13-19 -- Legal Aspects of Brain Death and Organ Donorship, Ricky T. Munoz, Mark D. Fox, Pages 21-35 -- Ethical Issues in Organ Donation from Brain-Dead Donors, Mark D. Fox, Ricky T. Munoz, Pages 37-53 -- Pathophysiology of Brain Death in Small Animal Models, Bernhard Floerchinger, Nicholas L. Tilney, Stefan G. Tullius, Pages 55-64 -- Pathophysiology of Brain Death and Effects of Hormonal Therapy in Large Animal Models, Dimitri Novitzky, Winston N. Wicomb, David K. C. Cooper, Pages 65-90 -- The Efficacy of Thyroid Hormone Therapy in Brain-Dead Heart Donors: A Review of Thyroid Function in Health and Disease, Lawrence E. Shapiro, Tatiana Baron, Pages 91-105 -- The Inflammatory Response to Brain Death, Anne Barklin, Christine Lodberg Hvas, Else Toennesen, Pages 107-119 -- The Influence of Brain Death and Intensive Care Management on Donor Organs: Assessment of Inflammatory Markers, Wayel Jassem, Susan V. Fuggle, Pages 121-129 -- Brain Death-Induced Inflammation: Possible Role of the Cholinergic Anti-inflammatory Pathway, Simone Hoeger, Benito A. Yard, Pages 131-138 -- Innate Immunity and Injury During Brain Death: Opportunities for Intervention, Marc A. Seelen, Henri G. D. Leuvenink, Rutger J. Ploeg, Pages 139-145 -- Selection of the Brain-Dead Potential Organ Donor, Kadiyala V. Ravindra, Keri E. Lunsford, Paul C. Kuo, Pages 147-154 -- Infectious Disease Aspects of the Brain-Dead Potential Organ Donor, Nicole M. Theodoropoulos, Michael G. Ison, Pages 155-176 -- Malignancy in the Brain-Dead Organ Donor, Michael A. Nalesnik, Ron Shapiro, Michael G. Ison, Pages 177-189 -- Early Clinical Experience of Hormonal Therapy in the Brain-Dead Potential Organ Donor, Dimitri Novitzky, Burcin Ekser, David K. C. Cooper, Pages 191-207 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in the USA, Demetrios Demetriades, Lydia Lam, Pages 209-216 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in Europe, Gabriel J. Echeverri, Bruno G. Gridelli, Pages 217-235 -- Assessment, Monitoring, and Management of Brain-Dead Potential Organ Donors in Australia, Peter S. Macdonald, Anders E. M. Aneman, Deepak Bhonagiri, Daryl A. Jones, Gerry O’Callaghan, Helen I. Opdam et al., Pages 237-249 -- Management of the Brain-Dead Organ Donor: Perspectives of the Transplant Coordinator, Nicole T. Farina, David K. C. Cooper, Pages 251-261 -- Surgical Aspects of Thoracic and Abdominal Organ Procurement from Brain-Dead Donors, Michael J. Anstadt, Paul C. Kuo, Kadiyala V. Ravindra, Pages 263-281 -- Impact of Brain Death on Storage of the Heart, Winston N. Wicomb, David K. C. Cooper, Pages 283-288 -- Impact of Brain Death on Abdominal Organs and Allograft Preservation Strategies, Coney Bae, Anthony Watkins, Scot D. Henry, James V. Guarrera, Pages 289-298 -- Functional Repair of Brain Death-Induced Injury, Henri G. D. Leuvenink, Marc A. Seelen, Rutger J. Ploeg, Pages 299-310 -- Functional Repair of Brain Death-Injured Donor Lungs, Jonathan C. Yeung, Marcelo Cypel, Shaf Keshavjee, Pages 311-320 -- Thyroid Hormone Therapy to the Recipient of a Heart from a Brain-Dead Donor, Dimitri Novitzky, David K. C. Cooper, Pages 321-331 -- Current and Potential Future Trends in the Management of the Brain-Dead Organ Donor, Octavio E. Pajaro, James K. Kirklin, Pages 333-341 -- Maximizing Utilization of the Potential Deceased Donor: The Challenge Continues,Eliezer Katz,Pages 343-35