title: A biphasic response to nitric oxide donation in an ex vivo model of donation after cardiac death renal transplantation.
abstract: BACKGROUND
  Donation after cardiac death (DCD) donors are vital to maximize the organ donor pool. Reperfusion injury (RI) is an important sequela in DCD organs due to warm and cold ischemia. RI manifests clinically as a high incidence of delayed graft function (DGF) and primary non-function (PNF) compared with donation after brain death organs. The importance of nitric oxide (NO) in the generation of reperfusion injury is pivotal.
  
  
  METHODS
  Using an ex vivo porcine model of kidney transplantation the effects of reperfusion with and without NO supplementation on initial renal blood flow and function were compared. Real-time hemodynamic measurements were recorded and biochemical samples taken at set time-points. Molecular markers of reperfusion injury were also measured. Sodium nitroprusside was chosen as the NO donor.
  
  
  RESULTS
  Results showed that NO donation initially improved renal blood flow significantly over controls; at the end of reperfusion this benefit was lost. In addition, there was an improvement in creatinine clearance, fractional excretion of sodium and renal oxygen consumption. There were observed to be higher levels of urinary nitrite/nitrate excretion, but no difference in isoprostane levels.
  
  
  CONCLUSIONS
  This study represents a good model for the initial reperfusion period in large animal renal transplantation. The improvement in renal blood flow observed in the NO supplemented groups represents NO mediated vasodilatation. Later in reperfusion, accumulation of nitrogenous free radicals impairs renal blood flow. Clinically, NO supplementation during initial reperfusion of DCD kidneys improves renal blood flow but should be considered with caution due to potential deleterious effects of nitrogenous compound accumulation.
authors: Department of Infection, Immunity and Inflammation, Transplant Group, University of Leicester, Leicester General Hospital, Leicester, UK. pjy4@hotmail.co.uk
authors: Phillip J
authors: PJ
authors: Yates
authors: Sarah A
authors: SA
authors: Hosgood
authors: Michael L
authors: ML
authors: Nicholson