Intraarterial Adenosine Administered During Reperfusion Preserves Endothelium-Dependent Relaxation in the Rabbit Hindlimb

Abstract

Consumption of adenosine triphosphate (ATP) during ischemia leads to the failure of cell membrane ATP-dependent ion pumps, cell lysis, and activation of the inflammatory cascade, which contributes to endothelial injury during reperfusion. Adenosine is a lipidsoluble precursor in ATP metabolism that may be depleted during reperfusion, exacerbating this injury. The purpose of this study was to examine the effect of adenosine administration with reperfusion on endothelium-dependent relaxation in the rabbit superficial femoral artery.

New Zealand white rabbits underwent 3 hours of complete unilateral hindlimb ischemia followed by 2 hours of reperfusion. Animals received an intraarterial infusion of adenosine (0.35 mg/kg/min) or an equivalent volume of normal saline (1 cc/min) during the first 20 minutes of reperfusion. A sham group underwent aortoiliac collateral ligation and 5 hours of anesthesia without ischemia. A control group underwent immediate superficial femoral artery explantation with no collateral ligation or prolonged anesthesia. The superficial femoral arteries were explanted and suspended as 3 mm segments upon isometric force transducers within organ bath chambers. Contraction was evaluated with potassium chloride (KCl) and maximal 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 group (P<0.05). A significant increase in relaxation was noted over four consecutive doses of Ach administered to vessels from the adenosine, sham, and control groups when compared with the saline group (P<0.05).

Adenosine administered during reperfusion preserved endothelium-dependent relaxation after ischemia and reperfusion in the rabbit superficial femoral artery. Adenosine may act as a substrate for ATP resynthesis and maintain cellular integrity during reperfusion. This form of pharmacologic therapy may prove clinically useful in the treatment of extremity ischemia/reperfusion injury.

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