Objective: To investigate the effects of extracorporeal cardiac shock wave therapy (CSWT) on myocardial perfusion and injury in rats with coronary microvascular dysfunction (CMD), and its potential role in preventing adverse myocardial remodeling. We further explored whether CSWT improves coronary microcirculation by promoting angiogenesis, enhancing endothelial function, and modulating microvascular tone, and examined the underlying mechanism involving the SIRT1/AMPK/eNOS signaling pathway.

Methods: An acute CMD model was established by injecting sodium laurate from the left ventricular apex into the left ventricle. After successful modeling, rats were randomized into four groups (n=8 each): CMD, CMD+CSWT, CMD+EX- 527+CSWT, and CMD+Compound C+CSWT. An additional eight rats received an equal volume of normal saline injection after thoracotomy and served as the sham group. On postoperative day 30, myocardial morphology was assessed by hematoxylin–eosin (H&E) staining, and fibrosis was quantified by Masson’strichrome staining. CD31 immunofluorescence was used to evaluate microvessel formation in ischemic myocardium. Serum obtained from the abdominal aorta was analyzed by ELISA for vasoactive factors (nitric oxide [NO], prostacyclin [PGI₂], endothelin-1 [ET-1], angiotensin II [Ang II]) and inflammatory cytokines (IL-1β, IL- 6, TNF-α). Myocardial tissue from the left anterior descending (LAD) coronary artery perfusion territory was subjected to Western blotting to determine the expression of SIRT1, AMPK, phosphorylated AMPK (p-AMPK), endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS (p-eNOS), thereby assessing the activity of theSIRT1/AMPK/eNOS pathway.

Results: H&E staining showed intact myocardial architecture with orderly alignment, clear nuclei, and no obvious necrosis or inflammatory infiltration in the sham group. In CMD-related groups, myocardial disarray, blurred striations, focal necrosis, old hemorrhage, inflammatory cell infiltration, and varying degrees of fibrosis were observed. Compared with the CMD group, the CMD+CSWT group exhibited attenuated myocardial injury and less fibrosis. Masson’s trichrome staining demonstrated a significantly lower collagen volume fraction (CVF) in the sham group than in all other groups, and CSWT significantly reduced CVF compared with CMD alone (P<0.05). Results of CD31 munofluorescence, ELISA indices, and Western blot analysis are to be completed to further define angiogenic changes, endothelial/vasoactive profiles, inflammatory status, and activation of the SIRT1/AMPK/eNOS pathway.

Conclusion: CSWT alleviates myocardial injury and fibrosis in rats with CMD, suggesting a potential protective effect against adverse myocardial remodeling. This benefit may be mediated, at least in part, by improved endothelial function and activation of the IRT1/AMPK/eNOS signaling pathway; definitive mechanistic conclusions require confirmation with complete CD31, ELISA, and Western blot

results.

To be updated