Vericiguat protects against cardiac damage in a pig model of ischemia/reperfusion

BACKGROUND: The purpose of this research was to verify that vericiguat, a soluble guanylate cyclase (sGC) stimulator, reduces myocardial ischemic reperfusion injury (MIRI), and to learn how this reduction happens. METHODS AND RESULTS: To develop an ischaemia/reperfusion (I/R) model, the left anterior descending artery was blocked in minipigs under anesthesia for 90 minutes, followed by 180 minutes of reperfusion. Vericiguat is administered three hours before surgery. Two weeks after receiving therapy, pigs underwent cardiovascular magnetic resonance imaging (MRI) to evaluate the results. The MRI results suggest improvement in the myocardial infarct after vericiguat treatment. Vericiguat treatment for two weeks enhanced vascularity, inhibited pro-inflammatory cells, and decreased collagen deposition in the infarct zone of pigs. Short-term experiments investigating possible explanations have indicated that vericiguat has antiapoptotic effects on cardiomyocytes and increases levels of autophagy. CONCLUSIONS: Vericiguat, an SGC activator, reduces MIRI in pigs by boosting autophagy, preventing apoptosis, and promoting angiogenesis.