On-pump inhibition of es-ENT1 nucleoside transporter and adenosine deaminase during aortic crossclamping entraps intracellular adenosine and protects against reperfusion injury: Role?of adenosine A1 receptor

详细信息    查看全文

• 作者：Anwar Saad Abd-Elfattah ; MS ; PhD ; FAHA ; AFSTS^a ; ^{anwar@vcu.edu} ; Mai Ding ; MD^b ; Michael E. Jessen ; MD ; FACS ; FSTS ; FAHA^c ; Andrew S. Wechsler ; MD ; FSTS ; FACS^d
• 关键词：ATP ; adenosine triphosphate ; DPCPX ; 8-cyclopentyl-1 ; 3-dipropyl-xanthine ; EHNA ; erythro-9 (2-hydroxy-3-nonyl)-adenine ; NBMPR ; p-nitro-benzylthioinosine ; SPT ; 8-(p-sulfophenyl)theophyline
• 刊名：The Journal of Thoracic and Cardiovascular Surgery
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：144
• 期：1
• 页码：243-249.e1
• 全文大小：405 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Objective

The inhibition of adenosine deaminase with erythro-9 (2-hydroxy-3-nonyl)-adenine (EHNA) and the es-ENT1 transporter with p-nitro-benzylthioinosine (NBMPR), entraps myocardial intracellular adenosine during on-pump warm aortic crossclamping, leading to a complete recovery of cardiac function and adenosine triphosphate (ATP) during reperfusion. The differential role of entrapped intracellular and circulating adenosine in EHNA/NBMPR-mediated protection is unknown. Selective (8-cyclopentyl-1,3-dipropyl-xanthine) or nonselective [8-(p-sulfophenyl)theophyline] A1 receptor antagonists were used to block adenosine A1-receptor contribution in EHNA/NBMPR-mediated cardiac recovery.

Methods

Anesthetized dogs (n?=?45), instrumented to measure heart performance using sonomicrometry, were subjected to 30 minutes of warm aortic crossclamping and 60 minutes of reperfusion. Three boluses of the vehicle (series A) or 100 ¦ÌM EHNA and 25 ¦ÌM NBMPR (series B) were infused into the pump at baseline, before ischemia and before reperfusion. 8-Cyclopentyl-1,3-dipropyl-xanthine (10 ¦ÌM) or 8-(p-sulfophenyl)theophyline (100 ¦ÌM) was intra-aortically infused immediately after aortic crossclamping distal to the clamp in series A and series B. The ATP pool and nicotinamide adenine dinucleotide was determined using high-performance liquid chromatography.

Results

Ischemia depleted ATP in all groups by 50 % . The adenosine/inosine ratios were more than 10-fold greater in series B than in series A (P?<?.001). ATP and function recovered in the EHNA/NBMPR-treated group (P?<?.05 vs control group). 8-Cyclopentyl-1,3-dipropyl-xanthine and 8-(p-sulfophenyl)theophyline partially reduced cardiac function in series A and B to the same degree but did not abolish the EHNA/NBMPR-mediated protection in series B.

Conclusions

In addition to the cardioprotection mediated by activation of the adenosine receptors by extracellular adenosine, EHNA/NBMPR entrapment of intracellular adenosine provided a significant component of myocardial protection despite adenosine A1 receptor blockade.