Overcoming severe renal ischemia: the role of ex vivo warm perfusion

Brasile, Lauren; Stubenitsky, Bart M.; Booster, M. H.; Lindell, Susanne L.; Araneda, D; Buck, Corinne; Bradfield, John F.; Haisch, Carl E.; Kootstra, G.

doi:10.1097/00007890-200203270-00011

Cited by 106 publications

(78 citation statements)

References 12 publications

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“…The ideal method of preservation should facilitate the use of extended criteria organs, initiate reparative processes for established donor organ injury and provide real-time quality assessment prior to transplantation. Machine preservation of solid organs is being proposed as a method that may achieve these goals (10)(11)(12)(13)(14). (15)(16)(17)(18)(19) (20)(21)(22).…”

Section: The Shortage Of Healthy Lungs For Transplantation Demands Opmentioning

confidence: 99%

Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation

Cypel

Rubacha

Yeung

et al. 2009

American Journal of Transplantation

231

164

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Treatment of injured donor lungs ex vivo to accelerate organ recovery and ameliorate reperfusion injury could have a major impact in lung transplantation.We have recently demonstrated a feasible technique for prolonged (12 h) normothermic ex vivo lung perfusion (EVLP). This study was performed to examine the impact of prolonged EVLP on ischemic injury. Pig donor lungs were cold preserved in Perfadex R for 12 h and subsequently divided into two groups: cold static preservation (CSP) or EVLP at 37• C with Steen TM solution for a further 12 h (total 24 h preservation). Lungs were then transplanted and reperfused for 4 h. EVLP preservation resulted in significantly better lung oxygenation (PaO 2 531 ± 43 vs. 244 ± 49 mmHg, p < 0.01) and lower edema formation rates after transplantation. Alveolar epithelial cell tight junction integrity, evaluated by zona occludens-1 protein staining, was disrupted in the cell membranes after prolonged CSP but not after EVLP. The maintenance of integrity of barrier function during EVLP translates into significant attenuation of reperfusion injury and improved graft performance after transplantation. Integrity of functional metabolic pathways during normothermic perfusion was confirmed by effective gene transfer and GFP protein synthesis by lung alveolar cells. In conclusion, EVLP prevents ongoing injury associated with prolonged ischemia and accelerates lung recovery.

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Section: The Shortage Of Healthy Lungs For Transplantation Demands Opmentioning

confidence: 99%

Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation

Cypel

Rubacha

Yeung

et al. 2009

American Journal of Transplantation

231

164

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“…Exsanguineous metabolic support (EMS) technology (Breonics Inc., Schenectady, NY) was used for ex vivo warm perfusion (32 C); a temperature range previously shown to adequately support oxidative metabolism and cellular reparative processes (18)(19)(20)(21)(22)(23)(24). Both human and canine kidneys were placed on a perfusion system including an oxygenator and a pulsatile pump, retrofitted with controllers to maintain PAO 2 , PACO 2 , pH and temperature.…”

Section: Methodsmentioning

confidence: 99%

“…During organ culture, retention of the normal barrier functions of the blood vessel wall has been previously shown to represent the essential component that prevents deterioration in the vascular dynamics (19) (Figure 3). During the culture of kidneys, the perfusion pressures and vascular flow rates remain stable and the organs do not become edematous (<15% net weight gain).…”

Section: Transplantation Following Ems Organ Culturementioning

confidence: 99%

“…When these canine kidneys were reimplanted following 18 h of organ culture, they provided immediate normal renal function (18). The EMS organ culture has also previously been shown to support resuscitation of oxidative metabolism in kidneys damaged by 2 h of warm ischemia, and when transplanted provided for immediate life sustaining function (19). However, in order for this technology to become clinically relevant it is necessary that longer ex vivo periods be achieved.…”

Section: Introductionmentioning

confidence: 99%

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NOS: The Underlying Mechanism Preserving Vascular Integrity and During Ex Vivo Warm Kidney Perfusion

Brasile

Stubenitsky

Booster

et al. 2003

American Journal of Transplantation

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Research involving metabolically active and functioning organs, maintained ex vivo in culture-like conditions, could provide numerous opportunities for medical innovations and research. We report successful perfusion of isolated canine and human kidneys ex vivo at near physiologic temperature for 48 h. During the perfusions parameters of metabolism and function remained stable. Nitric oxide synthase (NOS) was identified as the underlying mechanism preserving vascular integrity. Most importantly, when the canine kidneys were reimplanted there was immediate normal renal function. This report highlights the potential significance of whole organ culture using a warm temperature ex vivo perfusion and discusses medical applications that could be developed.

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“…More prolonged normothermic preservation periods have also been more beneficial than hypothermic techniques [100,101]. The only report of a normothermic kidney perfusion technique in clinical practice is by Hosgood and Nicholson [102].…”

Section: Normothermic Machine Perfusionmentioning

confidence: 99%