Direct Protective Effects of Dexmedetomidine Against Myocardial Ischemia-Reperfusion Injury in Anesthetized Pigs

Yamada, Osamu; Cho, Sungsam; Hara, Tetsuya; Shibata, Itsuko; Maekawa, Takuji; Ureshino, Hiroyuki; Sumikawa, Koji

doi:10.1097/shk.0b013e318254d3fb

Cited by 68 publications

(48 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This molecule also provides protection from ischemia/reperfusion injury [96]. These properties of dexmedomidine led to a study of its eicacy in sickle mice, and Calhoun et al found that transgenic sickle mice receiving dexmedomidine had improved analgesia [97].…”

Section: Other Targetsmentioning

confidence: 99%

“…Dexmedetomidine, a speciic 2 -adrenoreceptor agonist, provides anti-nociception independent of opioid receptor action and via inhibition of sensory neurons [96]. This molecule also provides protection from ischemia/reperfusion injury [96].…”

Section: Other Targetsmentioning

confidence: 99%

“…Recently, in a limited clinical trial, 18 SCD patients were treated with single dosage of triluoperazine a CaMKII inhibitor going up to 10 mg, and eight subjects reported almost 0% reduction in their chronic pain. This study established 10 mg as the toxicity limit, and the improvement in patients' health without any adverse efect warrants a randomized clinical trial to evaluate eicacy of this treatment strategy in SCD patients [9 ].Dexmedetomidine, a speciic 2 -adrenoreceptor agonist, provides anti-nociception independent of opioid receptor action and via inhibition of sensory neurons [96]. This molecule also provides protection from ischemia/reperfusion injury [96].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of Pain in Sickle Cell Disease

Aich¹,

Beitz²,

Gupta³

2016

Sickle Cell Disease - Pain and Common Chronic Complications

View full text Add to dashboard Cite

Pain is one of the most common features of sickle cell disease SCD lacking efective therapy. Pain in SCD is relatively more complicated than other conditions associated with pain requiring understanding of the pathobiology of pain speciic to SCD. The characterization of pain to deine the diverse modalities of nociception in SCD is currently under progress via human studies accompanied by transgenic mouse models of SCD. Sickle pathobiology characterized by oxidative stress, inlammation and vascular dysfunction contributes to both peripheral and central nociceptive sensitization via mast cell activation in the periphery, and reactive oxygen species and glial activation and endoplasmic reticulum stress in the spinal cord among other efectors. These efects are mediated via several cellular receptors, which can be targeted to produce positive therapeutic outcomes. In this chapter, we will discuss the present understanding of molecular mechanisms of SCD pain and outline the mechanism-based translational potential of novel actionable targets to treat SCD pain.Keywords: pain, sickle cell disease, neurogenic inlammation, substance P, mast cell . IntroductionPain is a hallmark feature of sickle cell disease SCD , which can start in infancy, leading to hospitalization, reduced survival and poor quality of life. Pain in SCD is unique because of unpredictable and recurrent episodes of acute pain due to vaso-occlusive crises VOC , in addition to chronic pain experienced by a majority of adult patients on a daily basis [1]. Treatment choices remain limited to opioids, which impose liabilities of their own including constipation, mast cell activation, fear of addiction and respiratory depression [2]. Moreover, signiicantly larger doses of opioids are required to treat pain in SCD as compared to other acute and chronic pain conditions [1]. Pain can be lifelong in SCD and may therefore inluence © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.cognitive function and lead to depression and anxiety, which can in turn promote the perception of pain [1].Treatment of chronic pain remains unsatisfactory overall, perhaps due to the diverse pathobiology in diferent diseases. Therefore, it is critical to understand the mechanisms speciic to the genesis of sickle pain to develop targeted therapies. Vascular dysfunction, inlammation, ischemia/reperfusion injury and oxidative stress in the wake of VOC can each evoke activation of the nociceptive nerve ibers leading to acute pain. On the other hand, con...

show abstract

Section: Other Targetsmentioning

confidence: 99%

Section: Other Targetsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mechanisms of Pain in Sickle Cell Disease

Aich¹,

Beitz²,

Gupta³

2016

Sickle Cell Disease - Pain and Common Chronic Complications

View full text Add to dashboard Cite

show abstract

“…In addition, several animal studies showed that hind limb I/R injury affected several organs, including the kidneys, liver and lungs. [3][4][5] The highly selective and potent a2-adrenergic agonist dexmedetomidine (DXM) is an effective sedative, anxiolytic, and analgesic agent 6 with protective effects against I/R injury in several organs, including the heart, 7 brain, 8 and kidneys, 9 probably due to the antioxidant and anti-inflammatory properties of the compound. [10][11][12] Curcumin (CUR) has a long history of therapeutic use in Indian and Chinese medicine and has several pharmacological properties, including antioxidant, anti-inflammatory, antiviral, antimicrobial, antifungal, as well as anticancer activities.…”

Section: Introductionmentioning

confidence: 99%

Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model

et al. 2016

View full text Add to dashboard Cite

Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n ¼ 10), dexmedetomidine (DEX) group (25 lg/kg dexmedetomidine, n ¼ 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 lg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p < 0.01 for all comparisons). The TOS activity levels in blood samples were significantly higher in Control group and than the other groups (p < 0.01 for all comparison). The OSI were found to be significantly increased in the control group compared to others groups (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in the sham, CUR, DEX, and CUR-DEX groups, compared with the control group (p < 0.01). Rat hind limb ischemia-reperfusion causes histopathological changes in the kidneys. Curcumin and dexmedetomidine administered intraperitoneally was effective in reducing oxidative stress and renal histopathologic injury in an acute hind limb I/R rat model. ARTICLE HISTORY

show abstract

“…Clinical evidence suggests that induced autonomic nervous system modulation during perioperative administration of DEX is associated with a trend towards improved cardiac outcomes following non-cardiac surgery. [1][2][3][4] Previous experiments on animals have shown the benefits of DEX administration in the ischemic heart. [5][6][7] Cardioprotective effects have also been reported in global ischemia of isolated rat hearts.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin–angiotensin–aldosterone system

Wang

Zhang

et al. 2014

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Introduction: Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α2-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigated whether dexmedetomidine induces cardioprotection against myocardial apoptosis injury. Methods: In order to assess the role of dexmedetomidine on myocardial apoptosis, we established a grave scalding rat model. Blood and myocardial tissue from the ventriculus sinister were harvested, then troponin, myocardial apoptosis, and expression of caspase-12, GRP78, and CHOP were assessed. Results: Dexmedetomidine significantly reduced myocardial apoptosis, improved functional recovery, and reversed myocardial injury induced by grave scalding. The heart rate in the five groups studied was significantly different (p < 0.05). The number of buffy-stained nucleoli in the myocardial cell was highest in the simple scald group. The expression of caspase-12 obviously increased in the simple scald group. The expression of GRP78 and CHOP increased in the simple scald and scald and 50 μg/kg dexmedetomidine groups (p < 0.05). Conclusions: The results show that dexmedetomidine (DEX) produces cardioprotection against myocardial apoptosis injury. DEX is not only a useful sedative, but also plays a pivotal role in anesthetic cardioprotection. The potential benefits of DEX protection in high risk cardiovascular patients undergoing surgery are enormous.

show abstract

Direct Protective Effects of Dexmedetomidine Against Myocardial Ischemia-Reperfusion Injury in Anesthetized Pigs

Cited by 68 publications

References 32 publications

Mechanisms of Pain in Sickle Cell Disease

Mechanisms of Pain in Sickle Cell Disease

Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model

The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin–angiotensin–aldosterone system

Contact Info

Product

Resources

About