Role of HTK solution in protecting cardiomyocytes against oxidative stress by upregulating Nrf2 during cardiac arrest and resuscitation: a rat model with a right thoracotomy

Abstract

Introduction

The objective of this study was to establish a rat model for cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation and to investigate the regulatory role of HTK solution in protecting cardiomyocytes against oxidative stress by upregulating Nrf2.

Methods

40 rats were randomly assigned to four groups: the control (Ctrl), the histidine–tryptophan–ketoglutarate (HTK), 4:1 blood cardioplegia (BC) and del Nido cardioplegia (DN) groups. The cardiopulmonary bypass (CPB) procedure was implemented and sustained for a duration of 1 hour. Subsequent to the cessation of CPB, the rats were subjected to monitoring and observation for an additional 2 hours. Following this observation period, the heart and blood samples were procured for subsequent analysis.

Results

The MDA was significantly higher in the HTK group, BC group, and DN group compared to the Ctrl group. The HTK group had lower MDA levels than the BC group. Regarding MPO activity, it increased in the HTK group, BC group, and DN group relative to the Ctrl group. Both the BC and DN groups exhibited elevated MPO levels compared to the HTK group. SOD levels were significantly lower in the HTK, BC, and DN groups compared to the Ctrl group. The HTK group had higher SOD levels than the BC group. With respect to miRNA-210-3P and Nrf2, the expression were more efficient in the HTK, BC, and DN groups compared to the Ctrl group. The BC and DN groups showed reduced expression efficiency over the HTK group. Western blot analysis indicated that the ratio of Nrf2 target was higher in the HTK group, BC group, and DN group in comparison to the Ctrl group. Both the BC and DN groups had lower protein content compared to the HTK group. Immunohistochemistry scoring of HIF1-α and nuclear Nrf2 revealed higher scores in the HTK, BC, and DN groups compared to the Ctrl group. The HTK group achieved higher scores than both the BC and DN groups.

Conclusion

Varied degrees of oxidative stress damage were exhibited by three distinct cardioplegia solutions. The HTK group demonstrated a superior antioxidant effect. The protective response of the HTK solution against oxidative stress may be linked to the up-regulation of Nrf2.