Nejvíce citovaný článek - PubMed ID 26047384
Neonatal rat hearts cannot be protected by ischemic postconditioning
The cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by nitric oxide (NO). During the early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury, contain higher levels of serum nitrates, and their resistance cannot be further increased by IPC or IPoC. NOS blocker (L-NAME) lowers their high resistance. Wistar rat hearts (postnatal Days 1 and 10) were perfused according to Langendorff and exposed to 40 min of global ischemia followed by reperfusion with or without IPoC. NO and reactive oxygen species donors (DEA-NONO, SIN-1) and L-NAME were administered. Tolerance to ischemia decreased between Days 1 and 10. DEA-NONO (low concentrations) significantly increased tolerance to I/R injury on both Days 1 and 10. SIN-1 increased tolerance to I/R injury on Day 10, but not on Day 1. L-NAME significantly reduced resistance to I/R injury on Day 1, but actually increased resistance to I/R injury on Day 10. Cardioprotection by IPoC on Day 10 was not affected by either NO donors or L-NAME. It can be concluded that resistance of the neonatal heart to I/R injury is NO dependent, but unlike in adult hearts, cardioprotective interventions, such as IPoC, are most likely NO independent.
- Klíčová slova
- DEA‐NONO, L‐NAME, SIN‐1, ischemic postconditioning, neonatal hearts, nitric oxide,
- MeSH
- donory oxidu dusnatého farmakologie MeSH
- ischemické přivykání metody MeSH
- ischemický postconditioning * metody MeSH
- krysa rodu Rattus MeSH
- molsidomin farmakologie analogy a deriváty MeSH
- myokard metabolismus MeSH
- NG-nitroargininmethylester * farmakologie MeSH
- novorozená zvířata * MeSH
- oxid dusnatý * metabolismus MeSH
- potkani Wistar * MeSH
- reperfuzní poškození myokardu * prevence a kontrola metabolismus MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- donory oxidu dusnatého MeSH
- molsidomin MeSH
- NG-nitroargininmethylester * MeSH
- oxid dusnatý * MeSH
Cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by mitochondrial-K-ATP channels and nitric oxide (NO). During early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and their resistance cannot be further increased by IPC or IPoC. Therefore, we have speculated, whether mechanisms responsible for high resistance of neonatal heart may be similar to those of IPC and IPoC. To test this hypothesis, rat hearts isolated on days 1, 4, 7, and 10 of postnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured. Hearts were exposed to 40 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by 5 cycles of 10-s ischemia. Mito-K-ATP blocker (5-HD) was administered 5 min before ischemia and during first 20 min of reperfusion. Another group of hearts was isolated for biochemical analysis of 3-nitrotyrosine, and serum samples were taken to measure nitrate levels. Tolerance to ischemia did not change from day 1 to day 4 but decreased on days 7 and 10. 5-HD had no effect either on neonatal resistance to I/R injury or on cardioprotective effect of IPoC on day 10. Significant difference was found in serum nitrate levels between days 1 and 10 but not in tissue 3-nitrotyrosine content. It can be concluded that while there appears to be significant difference of NO production, mito-K-ATP and ROS probably do not play role in the high neonatal resistance to I/R injury.
- Klíčová slova
- 3-Nitrotyrosine, Ischemic postconditioning, Mito-K-ATP channel, Neonatal rats, Nitrates, Tolerance to ischemia,
- MeSH
- draslíkové kanály metabolismus MeSH
- ischemický postconditioning * MeSH
- krysa rodu Rattus MeSH
- novorozená zvířata MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- reperfuzní poškození myokardu metabolismus patofyziologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- draslíkové kanály MeSH
- mitochondrial K(ATP) channel MeSH Prohlížeč
- oxid dusnatý MeSH