Uridine-5′-triphosphate (UTP) reduces infarct size and improves rat heart function after myocardial infarct

Smadar Yitzhaki, Asher Shainberg, Yelena Cheporko, Bernardo A. Vidne, Alex Sagie, Kenneth A. Jacobson, Edith Hochhauser

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously found that uridine 5′-triphosphate (UTP) significantly reduced cardiomyocyte death induced by hypoxia via activating P2Y2 receptors. To explore the effect of UTP following myocardial infarction (MI) in vivo we studied four groups: sham with or without LAD ligation, injected with UTP (0.44 μg/kg i.v.) 30 min before MI, and UTP injection (4.4 μg/kg i.v.) 24 h prior to MI. Left ventricular end diastolic area (LVEDA), end systolic area (LVESA) fractional shortening (FS), and changes in posterior wall (PW) thickness were performed by echocardiography before and 24 h after MI. In addition, we measured different biochemical markers of damage and infarct size using Evans blue and TTC staining. The increase in LVEDA and LVESA of the treated animals was significantly smaller when compared to the MI rats (p < 0.01). Concomitantly, FS was higher in groups pretreated with UTP 30 min or 24 h (56 ± 14.3 and 36.7 ± 8.2%, p < 0.01, respectively). Ratio of infarct size to area at risk was smaller in the UTP pretreated hearts than MI rats (22.9 ± 6.6, 23.1 ± 9.1%, versus 45.4 ± 7.6%, respectively, p < 0.001). Troponin T and ATP measurements, demonstrated reduced myocardial damage. Using Rhod-2-AM loaded cardiomyocytes, we found that UTP reduced mitochondrial calcium levels following hypoxia. In conclusion, early or late UTP preconditioning is effective, demonstrating reduced infarct size and superior myocardial function. The resulting cardioprotection following UTP treatment post ischemia demonstrates a reduction in mitochondrial calcium overload, which can explain the beneficial effect of UTP.

Original languageEnglish
Pages (from-to)949-955
Number of pages7
JournalBiochemical Pharmacology
Volume72
Issue number8
DOIs
StatePublished - 16 Oct 2006
Externally publishedYes

Keywords

  • Heart protection
  • Ischemia
  • P2Y receptors

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