Evaluating the effects of subnormothermic perfusion with AP39 in a novel blood-free model of ex vivo kidney preservation and reperfusio
Yükleniyor...
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
MDPI
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS-4 degrees C) or subnormothermic perfusion at 21 degrees C with Hemopure (H-21 degrees C), Hemopure + 200 nM AP39 (H200nM-21 degrees C) or Hemopure + 1 mu M AP39 (H1 mu M-21 degrees C). Then, kidneys were reperfused with Hemopure at 37 degrees C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM-21 degrees C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1 mu M-21 degrees C group at 1 h and 2h. During reperfusion, the H200nM-21 degrees C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM-21 degrees C group exhibited higher perfusate pO(2) levels than the other groups and significantly lower apoptotic injury than the H-21 degrees C and the H1 mu M-21 degrees C groups. Thus, subnormothermic perfusion at 21 degrees C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood-free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics.
Açıklama
This research was supported by Physicians Services Incorporated (PSI) Foundation (Grant #18-17) and the Kidney Foundation of Canada (Grant #180015).
Anahtar Kelimeler
Kidney Preservation, Kidney Transplantation, Hydrogen Sulfide (H2S), Normothermic Machine Perfusion, Cold Ischemia, Donation
Kaynak
İnternational Journal of Molecular Sciences
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
22
Sayı
13
Künye
Juriasingani, S., Jackson, A., Zhang, M. Y., Ruthirakanthan, A., Dugbartey, G. J., Sogutdelen, E., ... & Sener, A. (2021). Evaluating the effects of subnormothermic perfusion with AP39 in a novel blood-free model of ex vivo kidney preservation and reperfusion. International Journal of Molecular Sciences, 22(13), 7180.
