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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H2921    most recent 01191.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Zhu, Z. Articles by Buolamwini, J. K. Search for Related Content PubMed PubMed Citation Articles by Zhu, Z. Articles by Buolamwini, J. K.

Cardioprotective effects of novel tetrahydroisoquinoline analogs of nitrobenzylmercaptopurine riboside in an isolated perfused rat heart model of acute myocardial infarction

¹Department of Pharmaceutical Sciences, College of Pharmacy, and ²Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee

Submitted 10 November 2005 ; accepted in final form 2 February 2007

We have investigated the cardioprotective effects of novel tetrahydroisoquinoline nitrobenzylmercaptopurine riboside (NBMPR) analog nucleoside transport (NT) inhibitors, compounds 2 and 4, in isolated perfused rat hearts. Langendorff-perfused heart preparations were subjected to 10 min of treatment with compound 2, compound 4, or vehicle (control) followed by 30 min of global ischemia and 120 min of reperfusion. For determination of infarct size, reperfusion time was 180 min. At 1 µM, compounds 2 and 4 provided excellent cardioprotection, with left ventricular developed pressure (LVDP) recovery and end-diastolic pressure (EDP) increase of 82.9 ± 4.0% (P < 0.001) and 14.1 ± 2.0 mmHg (P < 0.03) for compound 2-treated hearts and 79.2 ± 5.9% (P < 0.002) and 7.5 ± 2.7 mmHg (P < 0.01) for compound 4-treated hearts compared with 41.6 ± 5.2% and 42.5 ± 6.5 mmHg for control hearts. LVDP recovery and EDP increase were 64.1 ± 4.2% and 29.1 ± 2.5 mmHg for hearts treated with 1 µM NBMPR. Compound 4 was the best cardioprotective agent, affording significant cardioprotection, even at 0.1 µM, with LVDP recovery and EDP increase of 76.0 ± 4.9% (P < 0.003) and 14.1 ± 1.0 mmHg (P < 0.03). At 1 µM, compound 4 and NBMPR reduced infarct size, with infarct area-to-total risk area ratios of 29.13 ± 3.17 (P < 0.001) for compound 4 and 37.5 ± 3.42 (P < 0.01) for NBMPR vs. 51.08 ± 5.06% for control hearts. Infarct size was more effectively reduced by compound 4 than by NBMPR (P < 0.02). These new tetrahydroisoquinoline NBMPR analogs are not only potent cardioprotective agents but are, also, more effective than NBMPR in this model.

cardioprotection; nucleoside transport inhibitors; left ventricular developed pressure; end-diastolic pressure; ischemia; reperfusion; adenosine potentiation; infarct size reduction