INTRAARTERIAL ADENOSINE ADMINISTERED DURING REPERFUSION PRESERVES ENDOTHELIUM-DEPENDENT RELAXATION IN THE RABBIT HINDLIMB

Consumption of adenosine triphosphate (ATP) during ischemia leads to t he failure of cell membrane ATP-dependent ion pumps, cell lysis, and a ctivation of the inflammatory cascade, which contributes to endothelia l injury during reperfusion. Adenosine is a lipid-soluble precursor in ATP metabolism that may be depleted during reperfusion, exacerbating this injury. The purpose of this study was to examine the effect of ad enosine administration with reperfusion on endothelium-dependent relax ation in the rabbit superficial femoral artery. New Zealand white rabb its underwent 3 hours of complete unilateral hindlimb ischemia followe d by 2 hours of reperfusion. Animals received an intraarterial infusio n of adenosine (0.35 mg/kg/min) or an equivalent volume of normal sali ne (1 cc/min) during the first 20 minutes of reperfusion. A sham group underwent aortoiliac collateral ligation and 5 hours of anesthesia wi thout ischemia. A control group underwent immediate superficial femora l artery explantation with no collateral ligation or prolonged anesthe sia. The superficial femoral arteries were explanted and suspended as 3 mm segments upon isometric force transducers within organ bath chamb ers. Contraction was evaluated with potassium chloride (KCl) and maxim al norepinephrine (NE). Acetylcholine (Ach) relaxation was determined after NE submaximal contraction. No difference in contractile response to KCl was observed among the four groups. A significant increase in contraction to maximum NE was observed for vessels in the adenosine gr oup (P<0.05). A significant increase in relaxation was noted over four consecutive doses of Ach administered to vessels from the adenosine, sl-ram, and control groups when compared with the saline group (P<0.05 ). Adenosine administered during reperfusion preserved endothelium-dep endent relaxation after ischemia and reperfusion in the rabbit superfi cial femoral artery. Adenosine may act: as a substrate for ATP resynth esis and maintain cellular integrity during reperfusion. This form of pharmacologic therapy may prove clinically useful in the treatment of extremity ischemia/reperfusion injury.