Article

Okada H, Kurita T, Mochizuki T, Morita K, Sato S: The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts

Department of Anaesthesiology and Intensive Care, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
Resuscitation (Impact Factor: 4.17). 09/2007; 74(3):538-45. DOI: 10.1016/j.resuscitation.2007.01.032
Source: PubMed

ABSTRACT

Dexmedetomidine is a highly specific and selective alpha-2 adrenergic agonist that is now widely used in the intensive care setting. Many intensive care unit (ICU) patients are at risk of respiratory or cardiac arrest. This study was conducted to determine whether dexmedetomidine exhibits a cardioprotective effect on global ischaemia and subsequent myocardial infarction.
Isolated rat hearts were subjected to 30 min of global ischaemia followed by 120 min reperfusion, with administration of 0, 1 and 10nM dexmedetomidine during the pre-ischaemic period (n=7 each group). Secondly, 1 microM yohimbine, an alpha-2 antagonist, was given during the pre-ischaemic period, alone or in combination with 10 nM dexmedetomidine (n=7 each group).
Dexmedetomidine administration reduced coronary flow significantly (103.6+/-4.7%, 77.9+/-3.7, 63.7+/-6.1%, of the baseline values for 0, 1 and 10 nM dexmedetomidine, respectively), and yohimbine administration reversed this effect (88.0+/-2.2%). Dexmedetomidine improved the infarct size at each concentration (45.3+/-3.6, 30.2+/-3.3, and 21.2+/-2.3% of the total left ventricular mass for 0, 1, and 10nM dexmedetomidine, respectively), which was also reversed by yohimbine (43.6+/-1.4%).
Dexmedetomidine exhibited a cardioprotective effect on global ischaemia in the isolated rat heart model, which was mediated by alpha-2 adrenergic stimulation.

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Available from: Toshiaki Mochizuki
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    • "Previous studies have demonstrated a beneficial effect of this drug in the brain, reducing oxidative stress markers in a rat model of subarachnoid hemorrhage [26]. It also protected against ischemia/reperfusion injury in tissues such as ovarian [27] or cardiac, [28] [29] whereas it did not show antioxidant effects on intestinal mucosa when administrated either before or after ischemia [24]. Our last finding involves BDNF, a growth factor that protects brain cells from ischemic death [30]. "
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    ABSTRACT: Aims: Dexmedetomidine is a selective agonist of α2-adrenergic receptors with clinical anesthetic and analgesic properties that has also shown neuroprotective effects on several models of brain injury. Because perioperative stroke and brain damage are frequent causes of death in critical care units, we aimed to investigate neuroprotective properties of dexmedetomidine using an in vitro model of cerebral ischemia. Main methods: Primary mixed rat brain cortical cultures were subjected to oxygen and glucose deprivation and treated with different doses of dexmedetomidine in order to analyze three conditioning strategies: preconditioning, intraconditioning and postconditioning. Key findings: All dexmedetomidine pre-, intra- and postconditioning treatments showed neuroprotective effects reducing brain cell necrosis, although only preconditioning showed antiapoptotic effects. Dexmedetomidine treatments also reduced IL-6 and TNF-α levels, especially in the preconditioning groups. Oxidative stress was attenuated with all dexmedetomidine preconditioning treatments, but only with the higher dose in the intraconditioning group, and no effects were observed in the postconditioning. All conditioning strategies increased BDNF levels. Significance: Dexmedetomidine-mediated neuroprotective effects in an in vitro model of cerebral ischemia involve the attenuation of inflammation and oxidative stress and the increment of BDNF expression.
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    • "Few studies have addressed the pharmacological mechanism involved in Dex-dependent cardioprotection [15] [16]. Given the biphasic vascular effects of vasoconstriction and vasodilatation of the drug at coronary vessels, it was first proposed that Dex could mimic the effect of ischemic preconditioning [17]. "
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    ABSTRACT: The alpha2-adrenergic receptor agonist Dexmedetomidine (Dex) is a sedative medication used by anesthesiologists. Dex protects the heart against ischemia-reperfusion (IR) and can also act as a preconditioning mimetic. The mechanisms involved in Dex-dependent cardiac preconditioning, and whether this action occurs directly or indirectly on cardiomyocytes, still remain unclear. The endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway and endothelial cells are known to play key roles in cardioprotection against IR injury. Therefore, the aims of this work were to evaluate whether the eNOS/NO pathway mediates the pharmacological cardiac effect of Dex, and whether endothelial cells are required in this cardioprotective action. Isolated adult rat hearts were treated with Dex (10nM) for 25min and the dimerization of eNOS and production of NO were measured. Hearts were then subjected to global IR (30/120min) and the role of the eNOS/NO pathway was evaluated. Dex promoted the activation of eNOS and production of NO. Dex reduced the infarct size and improved the left ventricle function recovery, but this effect was reversed when Dex was co-administered with inhibitors of the eNOS/NO/PKG pathway. In addition, Dex was unable to reduce cell death in isolated adult rat cardiomyocytes subjected to simulated IR. Cardiomyocyte death was attenuated by co-culturing them with endothelial cells pre-treated with Dex. In summary, our results show that Dex triggers cardiac protection by activating the eNOS/NO signaling pathway. This pharmacological effect of Dex requires its interaction with the endothelium.
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    • "Dex, which is a potent and selective agonist of a2 adrenergic receptors, has been shown to have beneficial effects on I/R injury in several tissues (Engelhard et al., 2003; Okada et al., 2007). Additionally, it has been reported to be cardioprotective against global ischaemia in the heart of isolated rat models (Okada et al., 2007). Fig. 1 Photomicrographs shows left testes. "
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    ABSTRACT: The aim of this study was to investigate the antioxidant properties of udenafil citrate (1.4 mg kg(-1) -2.8 mg kg(-1) ), dexmedetomidine 25 μg kg(-1) and piracetam 200 mg kg(-1) administered on ipsilateral/contralateral testes after ischaemia in a rat model of testicular torsion/detorsion (T/D) and define its protective effect histologically. Fifty-six Wistar albino rats were included and randomly assigned into 6 groups. No intervention was performed in control group (Group 1, n = 8) and in torsion/detorsion group, (Group 2, n = 8). Udenafil 1.4 mg kg(-1) was given to torsion/detorsion group (Group 3, n = 10), udenafil 2.8 mg kg(-1) was given to torsion/detorsion group (Group 4, n = 10), piracetam 200 mg kg(-1) was given to torsion/detorsion group (Group 5, n = 10) and dexmedetomidine 25 μg kg(-1) was given to torsion/detorsion group (Group 6, n = 10) intraperitoneally after 60 mins of testicular torsion. Biochemical and histopathological testicular injury were evaluated. When the tissue was examined by TOS values, Group 3, Group 4 and Group 5 were significantly lower than Group 2. In contrary Group 6 values were significantly higher than Group 2. The increasing doses of udenafil demonstrated antioxidant properties on the testis tissue and histopathological that protects the testicles.
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