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


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, Oct 07, 2015
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    • "Dexmedetomidine, an α2-adrenergic agonist, has been shown experimentally to prevent ischemia-reperfusion injury by producing vasodilation and is frequently used in anesthesia and intensive care practice [19, 29]. Apart from sedative, analgesic characteristics of dexmedetomidine it has been shown that it has the ability to relieve the lung injury caused by renal ischemia-reperfusion [30]. "
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    ABSTRACT: Purpose: This study was intended to investigate the effect of dexmedetomidine on oxidative stress response in pneumoperitoneum established in rats. Methods: Animals were randomized into three groups, group S: with no pneumoperitoneum, group P: with pneumoperitoneum established, and group D: given 100 mcg intraperitoneal dexmedetomidine 30 min before establishment of pneumoperitoneum. Plasma total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) activity were measured 30 min after conclusion of pneumoperitoneum. Results: The mean TOS level was significantly higher in group P than in the other two groups, and the TOS level was significantly higher in group D than in group S (P < 0.05). Plasma TAS level was found to be lower in group P than in the other two groups, and the TAS level was lower in group D than in group S (P < 0.05). Consequently, the OSI was significantly higher in group P than in groups D and S (P < 0.05). Conclusions: Ischemia-reperfusion phenomenon that occurs during pneumoperitoneum causes oxidative stress and consumption of plasma antioxidants. Dexmedetomidine decreases oxidative stress caused by pneumoperitoneum and strengthens the antioxidant defense system.
    01/2014; 2014:760323. DOI:10.1155/2014/760323
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    • "Dexmedetomidine hydrochloride may also offer a new paradigm in the pharmacological treatment of symptoms of distress at the end of life. Previous studies have shown that dexmedetomidine hydrochloride exhibits a protective effect in a number of tissues with IRI (10–12). Gu et al(13) observed that renal IR significantly induced pulmonary injuries, increased the wet/dry (W/D) ratio, enhanced MPO activities and increased ICAM-1 and TNF-α mRNA levels in mice. "
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    ABSTRACT: Reperfusion injury is tissue damage caused by the re-supply of blood following a period of ischemia in tissues. Intestinal ischemia-reperfusion injury (IRI) is an extremely common clinical event associated with distant organ injury. The intestine serves as the initial organ of multi-system organ dysfunction syndrome. It is extremely important to identify a method to protect against IRI, as it is a key factor associated with morbidity and mortality in patients. In the present study, the protective effects of pretreatment with dexmedetomidine hydrochloride were investigated. Rats were divided into six groups and models of intestinal ischemia were created in the five groups. Certain groups were pretreated with dexmedetomidine hydrochloride. The levels of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay in order to evaluate the injury. Tissue sections were stained with hematoxylin and eosin to visualize the damage. qPCR and western blotting were performed to examine the inflammatory status. Pretreatment with various doses of dexmedetomidine hydrochloride significantly reduced the pathological scores and the inflammatory reaction. The levels of TNF-α, IL-6, TLR4 and MyD88 were decreased in the dexmedetomidine hydrochloride treatment groups compared with those in the sham control and untreated ischemia reperfusion groups. The results of the present study indicate that pretreatment with dexmedetomidine hydrochloride may be a useful method of reducing the damage caused by IRI.
    Experimental and therapeutic medicine 12/2013; 6(6):1359-1364. DOI:10.3892/etm.2013.1317 · 1.27 Impact Factor
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    • "It is a highly selective, shorter-acting intravenous alpha-2 agonist with a remarkable binding specificity for the α2 adrenoceptor [11]. Dexmedetomidine has been shown to protect heart, brain, kidneys and lungs in laboratory studies [12,25-27]. Study has suggested that α2 adrenoceptors exist widely in the renal peri-tubular vasculatures, proximal and distal tubules [28]. "
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    ABSTRACT: And Objectives: The aim of this retrospective investigation was to study the relationships among chronic kidney disease, acute kidney injury (AKI), and potential benefits by post-bypass dexmedetomidine use in patients undergoing cardiac surgery. The patient data were reviewed from the institutional Society of Thoracic Surgeons National Adult Cardiac Surgery Database after IRB approval. 1,133 patients were identified and divided into two groups: those who received dexmedetomidine or those who did not during the post-bypass period. The postoperative outcomes include the incidence of AKI, any complication and all cause of mortality. Post-bypass dexmedetomidine use was associated with significantly reduced the incidence of total AKI (26.1% vs. 33.75%; adjusted OR, 0.7033; 95%CI, 0.540 to 0.916; p=0.0089). In addition, post-bypass dexmedetomidine use was more likely to reduce the incidence of AKI in these patients with preoperative normal kidney function (Stage1; 32.8% to 22.8%; p=0.0233) and mild CKD (Stage 2; 32.8% to 24.7; p=0.0003) after cardiac surgery. Post-bypass infusion of dexmedetomidine was associated with significantly reduced incidence of any complication and 30-day mortalities. Post-bypass dexmedetomidine use is associated with a significant reduction in the incidence of AKI, especially mild AKI in patients with preoperative normal renal function and mild CKD undergoing cardiac surgery.
    PLoS ONE 10/2013; 8(10):e77446. DOI:10.1371/journal.pone.0077446 · 3.23 Impact Factor
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