l-Arginine Improves Endothelial and Myocardial Function after Brain Death

Szabó, Gábor; Soós, Pál; Heger, Ulrike; Mandera, Susanne; Buhmann, Volker; Bährle, Susanne; Kohl, B.; Hagl, S.

doi:10.1097/01.tp.0000225778.49388.f5

Cited by 4 publications

(3 citation statements)

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“…Decreased circulating nitrite levels could be due to endothelial dysfunction as previously reported with BD 29 , and/or increased consumption which has also been reported in the setting of ischemic tissue injury 13 . In fact data showing that nitrite levels in the circulation rise and then fall despite continual administration over 2h of BD (Figure 1D) suggest that increased nitrite consumption is occurring.…”

Section: Discussionsupporting

confidence: 59%

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

Kelpke

Chen

Bradley

et al. 2012

Kidney International

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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 hours of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 hours 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 post transplantation compared to untreated brain dead animals. Gene microarray analysis after 2 hours of brain death without or with nitrite therapy showed the latter significantly altered the expression of about 400 genes. Ingenuity Pathway analysis indicated 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.

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Section: Discussionsupporting

confidence: 59%

“…Moreover, there is precedent for NO-based therapy to counter detrimental effects of BD. L-arginine therapy repletes NO-signaling and protected against BD dependent endothelial dysfunction and myocardial blood flow 29 .…”

Section: Introductionmentioning

confidence: 99%

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

Kelpke

Chen

Bradley

et al. 2012

Kidney International

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“…They hypothesized that nitric oxide supply improves endothelial function, because after infusion of L-arginine, the substrate for nitric oxide supply, the decrease in coronary blood flow was less pronounced. They concluded that enhancement of endogenous nitric oxide synthesis due to L-arginine treatment is beneficial for endothelial function and thus for myocardial performance after brain death (Szabo et al, 2006). Takada et al (1998) showed in a rat model, that experimentally induced explosive brain death is followed by an up-regulation of immunoregulatory and cell adhesion molecules (CAMs) compared to animals with non-explosive brain death).…”

Section: Brain Death Of Organ Donors Is the First Inducer Of Endothelial Dysfunction During The Process Of Transplantationmentioning

confidence: 99%

Vascular Signaling in Allogenic Solid Organ Transplantation – The Role of Endothelial Cells

et al. 2020

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Graft rejection remains the major obstacle after vascularized solid organ transplantation. Endothelial cells, which form the interface between the transplanted graft and the host's immunity, are the first target for host immune cells. During acute cellular rejection endothelial cells are directly attacked by HLA I and II-recognizing NK cells, macrophages, and T cells, and activation of the complement system leads to endothelial cell lysis. The established forms of immunosuppressive therapy provide effective treatment options, but the treatment of chronic rejection of solid organs remains challenging. Chronic rejection is mainly based on production of donor-specific antibodies that induce endothelial cell activation-a condition which phenotypically resembles chronic inflammation. Activated endothelial cells produce chemokines, and expression of adhesion molecules increases. Due to this pro-inflammatory microenvironment, leukocytes are recruited and transmigrate from the bloodstream across the endothelial monolayer into the vessel wall. This mononuclear infiltrate is a hallmark of transplant vasculopathy. Furthermore, expression profiles of different cytokines serve as clinical markers for the patient's outcome. Besides their effects on immune cells, activated endothelial cells support the migration and proliferation of vascular smooth muscle cells. In turn, muscle cell recruitment leads to neointima formation followed by reduction in organ perfusion and eventually results in tissue injury. Activation of endothelial cells involves antibody ligation to the surface of endothelial cells. Subsequently, intracellular signaling pathways are initiated. These signaling cascades may serve as targets to prevent or treat adverse effects in antibody-activated endothelial cells. Preventive or therapeutic strategies for chronic rejection can be investigated in sophisticated mouse models of transplant vasculopathy, mimicking interactions between immune cells and endothelium.

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Short- and long-term effects of brain death on post-transplant graft function in a rodent model†

Korkmaz

Loganathan

et al. 2014

Interactive CardioVascular and Thoracic Surgery

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l-Arginine Improves Endothelial and Myocardial Function after Brain Death

Abstract: L-arginine treatment prevents endothelial dysfunction and improves myocardial performance after BD via enhancement of endogenous nitric oxide synthesis.

Cited by 4 publications

References 20 publications

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

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

Vascular Signaling in Allogenic Solid Organ Transplantation – The Role of Endothelial Cells

Short- and long-term effects of brain death on post-transplant graft function in a rodent model†

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