The results show that vericiguat preconditioning and postconditioning reduced the area of I/R-induced myocardial infarction, rate of apoptosis, and release of myocardial markers (CK-MB, LDH, and cTnI); down-regulated the expression of TLR4, JNK, and BAX; up-regulated HSP90 and Bcl-2 expression; and simultaneously diminished the levels of inflammatory factors (IL-6, ICAM-1, TNF-α). Here, MAPK8 is linked to myocardial infarction.