Department of Pathophysiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Physiol Rep. 2024 Aug;12(15):e16147. doi: 10.14814/phy2.16147.
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.
缺血预处理（IPC）和缺血后处理（IPoC）在成人心脏中的心脏保护作用是由一氧化氮（NO）介导的。在早期发育阶段，大鼠心脏对缺血再灌注（I/R）损伤的抵抗力更高，含有更高水平的血清硝酸盐，并且其抵抗力不能通过 IPC 或 IPoC 进一步增加。NOS 阻滞剂（L-NAME）降低了它们的高抵抗力。根据 Langendorff 法灌注 Wistar 大鼠心脏（出生后第 1 天和第 10 天），并暴露于 40 分钟的全缺血，然后再灌注或不进行 IPoC。给予 NO 和活性氧供体（DEA-NONO、SIN-1）和 L-NAME。第 1 天和第 10 天之间，对缺血的耐受性降低。在第 1 天和第 10 天，低浓度的 DEA-NONO 显著增加了对 I/R 损伤的耐受性。SIN-1 增加了第 10 天对 I/R 损伤的耐受性，但第 1 天没有。L-NAME 显著降低了第 1 天对 I/R 损伤的抵抗力，但实际上增加了第 10 天对 I/R 损伤的抵抗力。第 10 天的 IPoC 对心脏的保护作用不受 NO 供体或 L-NAME 的影响。可以得出结论，新生儿心脏对 I/R 损伤的抵抗力是依赖于 NO 的，但与成人心脏不同，心脏保护干预措施，如 IPoC，很可能是不依赖于 NO 的。
