Perioperative ropivacaine conditioning may attenuate myocardial ischemia-reperfusion injury via macrophage polarization

Local anesthetics exert anti-inflammatory and cytoprotective effects beyond sodium-channel blockade. Whether perioperative ropivacaine conditioning confers cardioprotection during myocardial ischemia-reperfusion (MI/R) injury remains unclear. This study investigated the cardioprotective effects of ropivacaine and its association with macrophage polarization in a rat MI/R model. Male Sprague–Dawley rats were randomly assigned to four groups ( n = 8/group): Control, MI/R, MI/R + ropivacaine 1 mg/kg, and MI/R + ropivacaine 2 mg/kg. Ropivacaine or saline was administered intraperitoneally once daily for 7 days before MI/R induction. Plasma levels of myoglobin, CK-MB, and cardiac troponin I were measured to assess myocardial injury. Histopathological changes were evaluated by hematoxylin–eosin staining. Circulating M1 and M2 macrophage proportions were quantified by flow cytometry, and myocardial expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) was analyzed by Western blot. Myocardial ischemia–reperfusion markedly increased plasma myoglobin, CK-MB, and cardiac troponin I levels compared with controls ( P < 0.001, 0.020, and 0.025, respectively), accompanied by severe histopathological injury characterized by disrupted myocardial fibers and inflammatory infiltration. High-dose ropivacaine (2 mg/kg), but not low-dose treatment, reduced plasma myoglobin and troponin I levels compared with untreated MI/R animals ( P = 0.004 and 0.030) and improved myocardial histological appearance. MI/R also increased circulating M1 macrophage proportion and decreased M2 macrophages ( P = 0.013 and 0.044), whereas high-dose ropivacaine reversed these changes ( P = 0.001 and 0.040). Consistent with macrophage polarization, MI/R increased myocardial iNOS expression and reduced Arg-1 levels compared with controls (both P < 0.001), while high-dose ropivacaine decreased iNOS and increased Arg-1 expression (both P < 0.001), indicating a shift toward an anti-inflammatory phenotype. Perioperative ropivacaine conditioning attenuates myocardial ischemia - reperfusion injury in rats, potentially through modulation of macrophage polarization toward an anti-inflammatory phenotype. These findings suggest an additional immunomodulatory mechanism of ropivacaine that may be relevant to perioperative cardio-protection.