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: 3.96). 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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    • "The dose of DEX in the in vivo and in the ex vivo models was used according to the manufacturer's recommendation and Okada et al. [13], respectively. Fig. 3 "
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    ABSTRACT: Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α(2)-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30 min of regional ischemia followed by 120 min of reperfusion with dexmedetomidine before ischemia. The α(2)-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of α(2)-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and peri-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of α(2)-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine peri-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac α(2)-adrenergic receptor stimulation.
    Biochimica et Biophysica Acta 04/2012; 1822(4):537-45. DOI:10.1016/j.bbadis.2011.12.013 · 4.66 Impact Factor
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    ABSTRACT: Background: Preconditioning might protect the myocardium against ischemia/ reperfusion injury by reducing infarct size and preventing arrhythmias. Dexmedetomidine (DEX) is a highly selective α2-agonist used for sedoanalgesia in daily anesthetic practice. The cardioprotective effects of DEX on infarct size and on the incidence of arrhythmias observed after regional ischemia/reperfusion injury in vivo have not been reported.Objective: The aim of this study was to determine whether DEX exhibits a preconditioning effect and reduces infarct size and the incidence and duration of arrhythmias in a regional cardiac ischemia/reperfusion model in rats.Methods: Adult male Sprague-Dawley rats were anesthetized with sodium thiopental and mechanically ventilated (0.9 mL/100 g at 60 strokes/min) through a cannula inserted into the trachea after tracheotomy. Cardiac ischemia was then produced by ligating the left main coronary artery for 30 minutes, followed by a reperfusion period of 120 minutes. Blood pressure (BP) and heart rate (HR) were monitored and echocardiograms (ECGs) were performed. Arrhythmia was scored based on incidence and duration. The animals were randomly divided into 3 groups. The ischemic preconditioning (IPC) group underwent 5 minutes of ischemia followed by 5 minutes of reperfusion before the 30-minute ischemia/120-minute reperfusion period. In the DEX group, intraperitoneal (IP) DEX 1 mL (100 μg/kg) was administered 30 minutes before the ischemia/ reperfusion period. In the control group, IP saline 1 mL was administered 30 minutes before the ischemia/reperfusion period. After reperfusion, the heart was excised, demarcated with saline and ethanol to identify the occluded and nonoccluded myocardium, and cut into slices ~2 mm thick, that were then stained and placed between 2 glass plates. The risk zone and the infarct zone were compared between groups. The investigator assessing the infarcts was blinded to the study group.Results: Twenty-one adult (aged 4-6 months) male Sprague-Dawley rats weighing 280 to 360 g were included in the study; 7 rats were assigned to each group. BP, HR, and ECG readings were not significantly different between groups and did not change during the study. Arrythmias occurred during ischemia and reperfusion in all groups. The duration of the arrhythmias was significantly shorter and the arrhythmia score was significantly lower in the IPC group (all, P<0.05), compared with the control group; however, they were not significantly different in the DEX group. During the ischemic period, duration of ventricular tachycardia (VT) and ventricular premature contractions (VPC) in the DEX group was significantly longer than that observed in the IPC group (all, P<0.05). The duration of VPC was also significantly shorter than that observed in the control group (both, P<0.05). Duration of VT during the reperfusion period in the DEX group was significantly longer than that observed in both IPC and control groups (both, P<0.05). The mean (SD) percentage of damage was significantly lower in the IPC group (44.1% [2.0%]) and the DEX group (26.7% [2.0%]) compared with the control group (69.0% [3.0%]; both, P<0.05). The percentage of damage in the DEX group was also significantly lower compared with the IPC group (P<0.05).Conclusions: This small, experimental in vivo study found that DEX was associated with reduced infarct size in ischemia/reperfusion injury in regional ischemia in this rat model but had no effect on the incidence of arrhythmias. Future studies are needed to clarify these findings.
    Current Therapeutic Research 04/2008; 69(2):150–158. DOI:10.1016/j.curtheres.2008.04.003 · 0.45 Impact Factor
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