Cardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart.
Cardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart.
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DOI：
10.1016/s0008-6363(01)00360-1
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发表时间：
2001-10
影响因子：
10.8
通讯作者：
J. Peart;G. Matherne;R. J. Cerniway;J. Headrick
中科院分区：
文献类型：
--
作者：
J. Peart;G. Matherne;R. J. Cerniway;J. Headrick
Objectives:To characterize the ‘anti-ischemic’ effects of adenosine metabolism inhibition in ischemic–reperfused myocardium.Methods:Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 μMerythro-2-(2-hydroxy-3-nonyl)adenine; EHNA) adenosine kinase inhibition (10 μM iodotubercidin; IODO), or 10 μM adenosine. Hearts overexpressing A1adenosine receptors (A1ARs) were also studied.Results:EHNA treatment reduced ischemic contracture and post-ischemic diastolic pressure (14±2 vs. 20±1 mmHg), increased recovery of developed pressure (66±3 vs. 53±2%) and reduced LDH efflux (8.9±1.6 vs. 18.0±1.7 I.U./g). IODO also improved functional recovery (to 60±2%) and reduced LDH efflux (5.3±1.7 I.U./g), as did treatment with 10 μM adenosine. Protection with EHNA was reversed by co-infusion of IODO or 50 μM 8-ρ-sulfophenyltheophylline (adenosine receptor antagonist), but unaltered by 20 μM inosine+10 μm hypoxanthine. Similarly, effects of iodotubercidin were inhibited by EHNA and 8-ρ-sulfophenyltheophylline. A1AR overexpression exerted similar effects to EHNA and EHNA or IODO alone enhanced recovery while EHNA+IODO reduced recovery in transgenic hearts. Functional recoveries and xanthine oxidase reactant levels were unrelated in the groups studied.Conclusions:Adenosine deaminase or kinase inhibition protects from ischemia–reperfusion. Cardioprotection via these enzyme inhibitors requires a functioning purine salvage pathway and involves enhanced adenosine receptor activation. Reduced formation of inosine is unimportant in EHNA-mediated protection.
