Warm preflush with streptokinase improves microvascular procurement and tissue integrity in liver graft retrieval from non-heart-beating donors

Background Apart from the warm ischemic insult, integrity of liver grafts f rom non-heart-beating donors (NHBD) is additionally affected by microvascul ar alterations including erythrocyte aggregation and thrombus formation, wh ich might hamper appropriate equilibration of the preservation solution to the grafts microvasculature precluding cold preservation, Thus, the objecti ve of our study was to characterize microvascular perfusion quality of Univ ersity of Wisconsin (UW) solution during initial flushout of livers from NH BD rats, and to analyze the effects of an additional warm preflush with Rin ger's lactated solution (RL) and with RL containing streptokinase (SK). Methods, Cardiocirculatory arrest was induced by phrenotomy, Subsequent to 30 min of warm ischemia, livers were perfused via an aortic catheter by gra vity of 100 cm H2O either with 4 degrees C 100 ml UCV solution (UW, n = 7), or with 25 degrees C 30 mi RL preflush followed by 4 degrees C 100 mi UW s olution (RL+UW, n = 7), or with 25 degrees C 30 mi SK- (7500 IU) containing RL preflush and 4 degrees C 100 mi UW solution (SK/RL+UW, n = 6), Liver mi croperfusion was quantified using in situ fluorescence epi-illumination mic roscopy, Liver microcirculation of sham-operated living animals (n = 4) ser ved as controls, Enzyme release after a 24-hr cold preservation period was used as an indicator of graft integrity. Results, After 30 min of warm ischemia, microvascular perfusion of UW solut ion was found markedly altered when compared with that of sham-operated liv ing controls, as indicated by a significant reduction (P < 0,05) of acinar and sinusoidal perfusion. Preflush with RL (RL+UW) only slightly attenuated the acinar and sinusoidal perfusion deficits, whereas the addition of SK t o RL (SK/RL+UW) resulted in a significant improvement of microvascular graf t perfusion (P < 0.05). Accordingly, the increased enzyme release observed in solely UW-flushed fivers after 24 hr cold preseravtion was only slightly influenced by preflush with RL, but markedly attenuated (P < 0,05) by pref lush with RL containing SK. Conclusion, The additive fibrinolytic therapy using SK is effective to impr ove microvascular procurement of livers after warm ischemia and may thus re present a promising approach to attenuate parenchymal cell injury in liver graft retrieval from NHBD.