Adding pulsatile vascular stimulation to venous systemic oxygen persufflation of liver grafts.

The effect of adding pulsatility to gaseous oxygen persufflation during liver preservation was studied in an isolated rat liver model. Livers from male Wistar rats were retrieved 30 min after cardiac arrest of the donor and subjected to 18 h of cold storage. Some grafts were subjected to nonpulsatile or pulsatile gaseous oxygen persufflation. Graft viability was assessed thereafter upon warm reperfusion in vitro (n = 5 per group). Pulsatile persufflation significantly improved parenchymal integrity (enzyme release, bile flow) upon reperfusion, with respect to nonpulsatile persufflation or cold storage (CS) (e.g., max. release of alanine aminotransferase: 44 ± 10 vs. 178 ± 29 vs. 345 ± 100 U/L; pulsatile vs. nonpulsatile persufflation vs. CS).The effect was associated with the prevention of the ischemic decline in gene and protein expression of the vasoprotective Krüppel-like factor 2, increased perfusate levels of the endogenous vasodilator nitric oxide, and reduced portal vascular resistance upon reperfusion, while nonpulsatile persufflation was less effective (e.g., vascular resistance: 1235 ± 108 vs. 1607 ± 155 vs. 2215 ± 208 Pa s/mL; pulsatile vs. nonpulsatile persufflation vs. CS). In conclusion, pulsatile mechanostimulation of the hepatovasculature seems a genuine protective mechanism, affecting early graft recovery upon reperfusion.

[1]  T. Minor,et al.  Hypothermic reconditioning in organ transplantation , 2013, Current opinion in organ transplantation.

[2]  T. Minor,et al.  Energetic recovery in porcine grafts by minimally invasive liver oxygenation. , 2012, The Journal of surgical research.

[3]  Thomas M Suszynski,et al.  Persufflation (or gaseous oxygen perfusion) as a method of organ preservation. , 2012, Cryobiology.

[4]  T. Minor,et al.  Hypothermic Reconditioning of Porcine Kidney Grafts by Short-Term Preimplantation Machine Perfusion , 2012, Transplantation.

[5]  G. Garcı́a-Cardeña,et al.  Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers , 2012, Hepatology.

[6]  S. Chien,et al.  Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow , 2012, Proceedings of the National Academy of Sciences.

[7]  T. Minor,et al.  Hypothermic Reconditioning by Gaseous Oxygen Improves Survival After Liver Transplantation in the Pig , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  Zhiyong Lin,et al.  "Go with the flow": how Krüppel-like factor 2 regulates the vasoprotective effects of shear stress. , 2011, Antioxidants & redox signaling.

[9]  S. Tullius,et al.  Hypothermic kidney preservation: a remembrance of the past in the future? , 2011, Current opinion in organ transplantation.

[10]  J. Visvader,et al.  Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow. , 2010, Blood.

[11]  Yuzhi Zhang,et al.  Flow Cessation Triggers Endothelial Dysfunction During Organ Cold Storage Conditions: Strategies for Pharmacologic Intervention , 2010, Transplantation.

[12]  M. Kinkhabwala,et al.  Hypothermic Machine Preservation in Human Liver Transplantation: The First Clinical Series , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  T. Minor,et al.  Impaired autophagic clearance after cold preservation of fatty livers correlates with tissue necrosis upon reperfusion and is reversed by hypothermic reconditioning , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[14]  T. Minor,et al.  Energy charge restoration, mitochondrial protection and reversal of preservation induced liver injury by hypothermic oxygenation prior to reperfusion. , 2009, Cryobiology.

[15]  P. Friend,et al.  Normothermic perfusion: a mini-review. , 2009, Transplantation.

[16]  L. DeLeve Hepatic microvasculature in liver injury. , 2007, Seminars in liver disease.

[17]  T. Minor,et al.  Assessment of hepatic integrity after ischemic preservation by isolated perfusion in vitro: the role of albumin. , 2007, Cryobiology.

[18]  Shu Chien,et al.  Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific. , 2006, Biochemical and biophysical research communications.

[19]  Yuzhi Zhang,et al.  Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. , 2005, The Journal of clinical investigation.

[20]  H. Herbst,et al.  Endothelin‐A receptor antagonist reduces microcirculatory disturbances and transplant dysfunction after partial liver transplantation , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[21]  T. Asahara,et al.  Prevention of ischemia–reperfusion-induced hepatic microcirculatory disruption by inhibiting stellate cell contraction using rock inhibitor1 , 2003, Transplantation.

[22]  P. Clavien,et al.  ATP‐supplies in the cold‐preserved liver: A long‐neglected factor of organ viability , 2002, Hepatology.

[23]  M. Menger,et al.  Role of Microcirculation in Transplantation , 2000, Microcirculation.

[24]  M. Clemens,et al.  Functional significance of endothelin B receptors in mediating sinusoidal and extrasinusoidal effects of endothelins in the intact rat liver , 2000, Hepatology.

[25]  T. Minor,et al.  Gaseous oxygen for hypothermic preservation of predamaged liver grafts: fuel to cellular homeostasis or radical tissue alteration? , 2000, Cryobiology.

[26]  S. R. Datta,et al.  Cellular survival: a play in three Akts. , 1999, Genes & development.

[27]  T. Minor,et al.  Successful transplantation of porcine livers after warm ischemic insult in situ and cold preservation including postconditioning with gaseous oxygen. , 1998, Transplantation.

[28]  R. Groszmann,et al.  The hepatic circulation in health and disease: Report of a single‐topic symposium , 1998, Hepatology.

[29]  M. Menger,et al.  Biophysical aspects of liver aeration by vascular persufflation with gaseous oxygen. , 1997, Transplantation.

[30]  J. Roselló-Catafau,et al.  Liver ischemic preconditioning is mediated by the inhibitory action of nitric oxide on endothelin. , 1996, Biochemical and biophysical research communications.

[31]  T. Minor,et al.  Effects of taurine on liver preservation in UW solution with consecutive ischemic rewarming in the isolated perfused rat liver , 1995, Transplant international : official journal of the European Society for Organ Transplantation.

[32]  M. Vaubourdolle,et al.  Creatine kinase‐BB: A marker of liver sinusoidal damage in ischemia‐reperfusion , 1993, Hepatology.

[33]  S. Hayashi,et al.  Microvascular changes of the liver preserved in UW solution. Pathological and immunohistochemical examination. , 1992, Cryobiology.

[34]  C. Hunt,et al.  The mechanism of action of retrograde oxygen persufflation in renal preservation. , 1989, Transplantation.

[35]  S. Strasberg,et al.  SINUSOIDAL LINING CELL DAMAGE: THE CRITICAL INJURY IN COLD PRESERVATION OF LIVER ALLOGRAFTS IN THE RAT , 1988, Transplantation.

[36]  T. Minor,et al.  Cold preservation of fatty liver grafts: prevention of functional and ultrastructural impairments by venous oxygen persufflation. , 2000, Journal of hepatology.

[37]  T. Minor,et al.  Role of the hepatovasculature in free radical mediated reperfusion damage of the liver. , 1993, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.