Hydrogen peroxide preconditioning is of dual role in cardiac ischemia/reperfusion

Moderate reactive oxygen species (ROS) at reperfusion would trigger cardioprotection and various antioxidants for pharmacological preconditioning failed to achieve cardioprotection. The causes for different roles of preischemic ROS during cardiac ischemia/reperfusion (I/R) require reevaluation. We investigated the precise role of ROS and its working model in this study. Different doses of hydrogen peroxide (H₂O₂, the most stable form of ROS) were added 5 min before ischemia using isolated perfused rat hearts, only moderate-dose H₂O₂ preconditioning (H₂O₂PC) achieved contractile recovery, whereas the low dose and high dose led to injury. Similar results were observed in isolated rat cardiomyocytes on cytosolic free Ca²⁺ concentration ([Ca²⁺]_c) overload, ROS production, the recovery of Ca²⁺ transient, and cell shortening. Based on the data mentioned above, we set up a mathematics model to describe the effects of H₂O₂PC with the fitting curve by the percentage of recovery of heart function and Ca²⁺ transient in I/R. Besides, we used the two models to define the initial thresholds of H₂O₂PC achieving cardioprotection. We also detected the expression of redox enzymes and Ca²⁺ signaling toolkits to explain the mathematics models of H₂O₂PC in a biological way. The expression of tyrosine 705 phosphorylation of STAT3, Nuclear factor E2-related factor 2, manganese superoxide dismutase, phospholamban, catalase, ryanodine receptors, and sarcoendoplasmic reticulum calcium ATPase 2 were similar with the control I/R and low-dose H₂O₂PC but were increased in the moderate H₂O₂PC and decreased in the high-dose H₂O₂PC. Thus, we concluded that preischemic ROS are of dual role in cardiac I/R.