Possible role of mitochondrial K-ATP channel and nitric oxide in protection of the neonatal rat heart

Jan Doul,Marcela Rašková,Bohuslav Ošťádal,Ivana Ošťádalová,Hana Maxová,Dana Miková,Zuzana Charvátová

doi:10.1007/s11010-018-3370-4

Abstract

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.

Highlights

Cardiac ischemia is the leading cause of morbidity and mortality in developed countries
The data concerning the development of cardioprotective effect of ischemic postconditioning (IPoC) would suggest the possible interference of IPoC mechanisms with the high resistance of neonatal hearts
One of the cardioprotective mechanisms involved in the effect of IPoC in adult hearts is mito-K-ATP channel

Summary

Introduction

Cardiac ischemia is the leading cause of morbidity and mortality in developed countries. We have shown previously that the above protective interventions were not able to increase already high cardiac tolerance to acute ischemia in neonatal rats; the first signs of protection were observed only at the beginning of the second postnatal week [3,4,5]. From these protective interventions, IPoC is the most promising for clinical use [6].

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Conclusion