Pre‐Conditioning and Post‐Conditioning of Ischemia Reperfused Rat Hearts: Sustained Protection in Normal Hearts; Ineffective in PM2.5 Exposed Hearts Due to Toxicity

ABSTRACT The present study addresses the toxicological impact of Particulate matter (PM 2.5 ) exposure on the pharmacological efficacy of ischemia preconditioning (IPC) and postconditioning (POC) against ischemia‐reperfusion (IR) injury. The primary motivation for this study is the gap in knowledge regarding the effectiveness of IPC and POC in PM 2.5 modified hearts. With the increasing prevalence of cardiac procedures involving IR and PM 2.5 toxicity, there is a growing need to understand their interaction. Female Wistar rats were subjected to PM 2.5 exposure for 3 h daily over a period of 21 days. Subsequently, their hearts were excised and mounted on a Langendorff perfusion apparatus. Three cycles of IPC and POC were applied, followed by the IR protocol. In contrast to hearts under normal conditions, neither IPC nor POC could reduce cardiac injury (infarct size, apoptosis, and inflammation) or enhance cardiac function in PM 2.5 ‐exposed hearts subjected to IR. The underlying reason for this ineffectiveness was identified as the inability to improve mitochondrial bioenergetic function and the expression of the declined master regulator gene Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1‐α). Additionally, the compromised mitochondrial quality control genes resulting from PM 2.5 exposure could not be restored to their normal levels by these conventional strategies. Furthermore, the crucial pro‐survival signaling pathways like phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) could not be reactivated by these strategies in PM 2.5 ‐exposed hearts undergoing IR, consequently preventing the restoration of cardioprotection. From the above results, we deduce that the therapeutic benefits of mechanical conditioning techniques such as IPC and POC were compromised in hearts exposed to PM 2.5 , primarily attributed to PM 2.5 induced mitochondrial dysfunction.