title: Improvement of microvascular graft equilibration and preservation in non-heart-beating donors by warm preflush with streptokinase.
abstract: Using in situ fluorescence microscopy with Sprague Dawley rats, we studied the hypothesis of compromised microvascular kidney perfusion on organ harvest in non-heart-beating donors (NHBDs), and we evaluated the potential benefit of an additional preflush with saline solution containing streptokinase. Aortal flush of NHBD kidneys solely with University of Wisconsin solution resulted in a significantly (P <0.05) reduced functional capillary density (FCD) with increased perfusion heterogeneity compared with kidneys of heart-beating controls. This was associated with an increased lactate dehydrogenase (LDH) release on 24 hr postpreservation rinse of the grafts (76.7+/-18.9 U/L). Warm preflush with low-viscosity Ringer's lactate (RL) solution alone did not influence the decreased renal FCD and the postpreservation LDH release (76.2+/-29.1 U/L). In contrast, the addition of streptokinase to the RL preflush solution resulted in a significant (P <0.05) improvement of FCD with values not statistically different from those of heart-beating controls. This was associated with an attenuation of perfusion heterogeneity and a significantly lowered postpreservation LDH release (17.0+/-2.5 U/L). Furthermore, in transplanted and reperfused NHBD kidney grafts, the use of streptokinase-supplemented RL for preflush during organ harvest significantly (P <0.05) reduced early manifestation of tubular necrosis (29%+/-8%) when compared with kidneys preflushed exclusively with University of Wisconsin solution (56%+/-4%). Thus, we conclude that kidney harvest from NHBDs is prone to severe microvascular perfusion deficits, which are likely to preclude successful preservation of organ integrity during cold storage. Temporary fibrinolytic preflush with streptokinase may represent a feasible tool to improve microvascular graft equilibration, which effectively protects the renal integrity during both cold storage and posttransplant reperfusion.
authors.affiliation: Institute for Clinical & Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Yamauchi
authors.forename: Rene
authors.initials: R
authors.lastname: Schramm
authors.forename: Sven
authors.initials: S
authors.lastname: Richter
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Thomas
authors.initials: T
authors.lastname: Minor
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D006323:Heart Arrest; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000601:surgery; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008833:Microcirculation; D019188:Organ Preservation Solutions; D010477:Perfusion; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy; D012965:Sodium Chloride / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D012965:Sodium Chloride; D000493:Allopurinol; D013300:Streptokinase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose