Remote ischemic preconditioning protects heart via modulation of purinergic signaling and AMPK-mediated autophagy in rat model of ischemia reperfusion injury

Articles in Press

Document Type : Original Article

Authors

1 Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, (Punjab)-147002, India

2 Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi-110029-India

10.22038/ijbms.2026.87896.18983

Abstract

Objective(s): Remote ischemic preconditioning (RIPC) represents a non-invasive, clinically applicable conditioning technique that mitigates myocardial ischemia-reperfusion injury (MIRI). Among various molecular mediators, the adenosine A1 receptor (AA1R) has emerged as a pivotal regulator of cardioprotective signaling. Currently, our aim is to elucidate the contribution of AA1R and AMPK-mediated autophagy in RIPC-induced cardioprotection.
Materials and Methods: Prolonged ischemia of 30 min and sustained reperfusion of 120 min were given to isolated hearts of rats using the Langendorff perfusion system to induce MIRI. RIPC was elicited through four intermittent phases of 5-minute hind-limb ischemia and 5-minute reperfusion using a pressure cuff. The role of AA1R and AMPK was investigated via pharmacological inhibition using DPCPX (selective AA1R antagonist) and BML-275 (AMPK inhibitor), respectively.
Results: IRI-induced myocardial damage was manifested by a substantial rise in infarct size, elevated levels of cardiac-specific markers, i.e., LDH-1, CK-MB, C-tPn-I, altered hemodynamic parameters (decreased HR, CFR, LVDP, RPP, +dp/dtmax, and -dp/dtmin), and other biochemical markers (increased TBARS, decreased GSH and catalase, increased TNF-α, TGF-β, Bax, and caspase-3). RIPC significantly attenuated these deleterious alterations, restoring both biochemical and functional parameters. However, the administration of DPCPX and BML-275 markedly abrogated the cardioprotective benefits conferred by RIPC.
Conclusion: These findings substantiate that RIPC exerts potent cardioprotective effects via activation of AA1R and AMPK-dependent autophagic signaling. The observed interplay between AA1R and AMPK underscores an integrated adaptive mechanism that preserves myocardial integrity during IRI. This mechanistic insight provides a rationale for exploring AA1R-AMPK axis modulation as a therapeutic avenue for clinical cardioprotection. 

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References

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Iranian Journal of Basic Medical Sciences

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Available Online from 16 February 2026

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