Journal article
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
The Journal of thoracic and cardiovascular surgery, v 144(1), pp 243-249
Jul 2012
PMID: 22325325
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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 μM EHNA and 25 μM NBMPR (series B) were infused into the pump at baseline, before ischemia and before reperfusion. 8-Cyclopentyl-1,3-dipropyl-xanthine (10 μM) or 8-(p-sulfophenyl)theophyline (100 μM) 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.
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.
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.
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Details
- Title
- 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
- Creators
- Anwar Saad Abd-Elfattah - Virginia Commonwealth University Medical CenterMai Ding - St. Johns HospitalMichael E Jessen - The University of Texas Southwestern Medical CenterAndrew S Wechsler - Drexel University
- Publication Details
- The Journal of thoracic and cardiovascular surgery, v 144(1), pp 243-249
- Publisher
- Elsevier
- Grant note
- R01 HL 05-1090 / NHLBI NIH HHS R01 HL051090-04 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000305412200040
- Scopus ID
- 2-s2.0-84862632575
- Other Identifier
- 991019168960204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Respiratory System
- Surgery