Amelioration of myocardial ischemia/reperfusion injury in diabetes: A narrative review of the mechanisms and clinical applications of dexmedetomidine

Abstract

Mechanisms contributing to the pathogenesis of myocardial ischemia-reperfusion (I/R) injury are complex and multifactorial. Many strategies have been developed to ameliorate myocardial I/R injuries based on these mechanisms. However, the cardioprotective effects of these strategies appear to diminish in diabetic states. Diabetes weakens myocardial responses to therapies by disrupting intracellular signaling pathways which may be responsible for enhancing cellular resistance to damage. Intriguingly, it was found that Dexmedetomidine (DEX), a potent and selective α2-adrenergic agonist, appears to have the property to reverse diabetes-related inhibition of most intervention-mediated myocardial protection and exert a protective effect. Several mechanisms were revealed to be involved in DEX’s protection in diabetic rodent myocardial I/R models, including PI3K/Akt and associated GSK-3β pathway stimulation, endoplasmic reticulum stress (ERS) alleviation, and apoptosis inhibition. In addition, DEX could attenuate diabetic myocardial I/R injury by up-regulating autophagy, reducing ROS production, and inhibiting the inflammatory response through HMGB1 pathways. The regulation of autonomic nervous function also appeared to be involved in the protective mechanisms of DEX. In the present review, the evidence and underlying mechanisms of DEX in ameliorating myocardial I/R injury in diabetes are summarized, and the potential of DEX for the treatment/prevention of myocardial I/R injury in diabetic patients is discussed.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

“…Diabetes is an independent risk factor of ischemic heart disease. It aggravates the MIRI and the main cause of death of diabetes patients 10 . Finding drugs that can effectively reduce the MIRI of diabetes is one of the focuses of the current research.…”

Protective Effect and Mechanism of Dexmedetomidine Pretreatment Mediated AMPK Pathway on Hypoxic Reoxygenation Injury in Rat Cardiomyocytes

“…Therefore, taking scientific and effective treatment measures to prevent myocardial hypoxia-reoxygenation injury is instrumental in enhancing the prognosis of individuals afflicted with myocardial infarction. It has been found that after the occurrence of hypoxic-ischemic myocardial injury, the body initiates a series of sequence reactions, including apoptosis, inflammation, disturbance of energy metabolism, oxidative stress and so on [8,9] .…”

Brown adipose tissue-derived FGF21 mediates the cardioprotection of dexmedetomidine in myocardial ischemia/reperfusion injury

“…Dexmedetomidine (DEX), a highly selective α-adrenergic receptor agonist, is widely used in clinical practice. DEX can be used in combination with other narcotic drugs to achieve better analgesia, sedation and adverse stress control during coronary artery bypass surgery [24]. Studies have shown that DEX could promote cardiomyocyte survival by activating PI3K/AKT, SIRT1/mTOR, MAPK/ERK and AMPK signaling pathways [25][26][27][28].…”