THE EFFECTS OF ADMINISTERING QUINACRINE DURING ULTRAPROFOUND HYPOTHERMIA ON WARM ISCHEMIC KIDNEY CORTEX TISSUE

Recent advances have led to increased use of ultraprofound hypothermia for cardiopulmonary bypass, organ preservation and trauma patients an d have introduced the possibility of targeted pharmacologic interventi on during the hypothermic period. In this study, rabbit renal cortex s lices were used to examine the effect of administering quinacrine (100 mu M) during hypothermia induced after a warm ischemic injury (60 min at 37 degrees C) on recovery of biochemical function during 3.5 hr of simulated warm reperfusion. In ischemic tissue slices, ATP content wa s reduced to near zero and only recovered about 50% by the end of repe rfusion. Hypothermic storage of ischemic slices for 18 hr restored sli ce ATP content to about 80% of control levels but was followed by a de cline during reperfusion to levels similar to ischemic slices. Adminis tering quinacrine (100 mu M) during 18 hr of hypothermic storage of is chemic slices resulted in a significant and sustained increase in slic e ATP content during warm reperfusion. Slices stored at hypothermia on ly 3 hr with quinacrine had reduced swelling during reperfusion even t hough total ATP content was unaffected. Administering quinacrine (100 mu M) only during reperfusion after ischemia or hypothermia did not af fect tissue ATP content. This study showed that drug administration du ring hypothermic storage has potential therapeutic benefits for resusc itating tissues after warm ischemia and is more effective than the sam e drug given only during reperfusion. Tissue pretreatment was not requ ired to obtain improved function in this study which suggests that fut ure adaptations of these principles may have practical applications fo r specific clinical conditions where ischemic and reperfusion injury a re significant factors.