Key result
Dexmedetomidine preconditioning improved cardiac function, reduced infarct size, and inhibited ferroptosis in rat myocardium after ischemia-reperfusion injury via α2 adrenergic receptor activation.
Why the study?
Previous studies on Dex protecting against MIRI by inhibiting ferroptosis were based on post-conditioning, and whether Dex preconditioning prevents MIRI via α2 adrenergic receptors was unclear.
Does dexmedetomidine preconditioning prevent myocardial ischemia-reperfusion injury by attenuating ferroptosis via α2 adrenergic receptor activation in rats?
RCT
randomly assigned
Does dexmedetomidine preconditioning prevent myocardial ischemia-reperfusion injury by attenuating ferroptosis via α2 adrenergic receptor activation in rats?
Dexmedetomidine preconditioning protects against myocardial ischemia-reperfusion injury in rats by attenuating ferroptosis via α2 adrenergic receptor activation and modulating the Nrf2/SLC7A11/GPX4 pathway.
Does not support clinical use; hypothesis-generating for α2-mediated ferroptosis inhibition in human ischemia-reperfusion.
Objective: Dexmedetomidine (Dex) is a potent agonist of the α2 adrenergic receptor that has been shown to possess sedative and hypnotic properties. Dex can protect against myocardial ischemia-reperfusion injury (MIRI) by inhibiting ferroptosis. However, these studies were based on Dex post-conditioning, and the role of α2 adrenergic receptors in this process is unclear. In this study, we investigated whether Dex preconditioning can prevent MIRI by attenuating ferroptosis and whether this effect depends on α2 adrenergic receptors in rats. Methods: Male Sprague-Dawley rats were randomly assigned to five groups: sham (saline-treated), I/R (ischemia-exposed), Dex + I/R (Dex pre-treatment), Dex + Yoh + I/R (Dex and yohimbine pre-treatment), and Yoh + I/R (yohimbine pre-treatment). Cardiac function, myocardial infarction, and morphological changes were assessed. Transmission electron microscopy was used to analyze mitochondrial morphology. Ferroptosis-related indicators and lipid peroxidation were measured using western blotting and qRT-PCR. Results: Our findings indicated that Dex preconditioning improved cardiac function, reduced infarct size and apoptosis, and inhibited ferroptosis in the rat myocardium after MIRI. These effects were associated with the upregulation of Nrf2, SLC7A11, and GPX4 expression, as well as the downregulation of Ferritin, TFR1, ACSL4, COX2, IL-1β, IL-6, and TNF-α expression. Importantly, yohimbine, an α2 adrenergic receptor antagonist, abolished these protective effects. Conclusion: These results suggest that Dex preconditioning can prevent MIRI by attenuating ferroptosis via α2 adrenergic receptor activation and by modulating the Nrf2/SLC7A11/GPX4 pathway.
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Wang et al. (2024) conducted an RCT in myocardial ischemia-reperfusion injury (MIRI). Dexmedetomidine preconditioning vs. sham, I/R, Dex + Yoh + I/R, and Yoh + I/R was evaluated on Cardiac function, myocardial infarction, and ferroptosis. Dexmedetomidine preconditioning improved cardiac function, reduced infarct size, and inhibited ferroptosis in rat myocardium after ischemia-reperfusion injury via α2 adrenergic receptor activation.
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