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  • Title: Effects of adenosine, an adenosine-A1 antagonist, and their combination in splanchnic occlusion shock in rats.
    Author: Karasawa A, Rochester JA, Lefer AM.
    Journal: Circ Shock; 1992 Feb; 36(2):154-61. PubMed ID: 1582007.
    Abstract:
    Splanchnic artery occlusion (SAO) with reperfusion results in a severe form of circulatory shock. To study the possible involvement of adenosine in this shock state, we have examined the effects of adenosine, an adenosine A1-receptor antagonist, and their combination in a rat model of SAO shock. Pentobarbital-anesthetized rats were subjected to a 90-min occlusion of both the celiac and superior mesenteric arteries followed by reperfusion. Rats given only the vehicle for adenosine (i.e., 0.9% NaCl) developed severe hypotension following reperfusion, and the survival rate was less than 30% 2 hr after reperfusion. Final plasma free amino-nitrogen concentrations, cathepsin D and myocardial depressant factor (MDF) activities were significantly elevated in rats receiving only the vehicle. Infusion of adenosine (i.e., 30 micrograms/kg/min, i.v.), starting 45 min postocclusion, did not significantly improve the survival rate but did attenuate the accumulation of MDF. Eighty percent (i.e., 4 of 5) rats given KF15372, an adenosine A1-antagonist, 45 min postocclusion (500 micrograms/kg), survived 2 hr. KF15372 also attenuated the increased plasma free amino-nitrogen and MDF. Seventy-five percent (i.e., 6 of 8) rats treated with KF15372 and adenosine survived 2 hr. This combined treatment significantly attenuated the increased plasma levels of free amino-nitrogen, cathepsin D, and MDF. These results suggest that endogenous adenosine plays a significant role in the pathogenesis of shock following SAO and reperfusion, and that blockade of the adenosine A1-receptor could be beneficial in shock states.
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