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Manjeet Singh - One of the best experts on this subject based on the ideXlab platform.

  • Modulation of the Cardioprotective Effect of ischemic preconditioning in hyperlipidaemic rat heart
    European journal of pharmacology, 2010
    Co-Authors: Harlokesh Narayan Yadav, Manjeet Singh, Pyare Lal Sharma
    Abstract:

    Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthaes kinase-3beta (GSK-3beta) that inhibits the opening of mitochondrial permeability transition pore (MPTP), and this Cardioprotective action of IPC is attenuated by hyperlipidaemia. The present study investigated the role of GSK-3beta in attenuation of Cardioprotective Effect of IPC, by hyperlipidaemia in the rat heart. Hyperlipidaemia was produced in rat by feeding high fat diet for six weeks. Isolated perfused rat heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed from coronary effluent. IPC significantly decreased the myocardial infarct size and the release of LDH and CK-MB from normal rat heart. IPC induced myocardial protection was attenuated in hyperlipidaemic rat heart. However, Cardioprotective Effect of pharmacological preconditioning with GSK-3beta inhibitors i.e. Lithium Chloride (LiCl) (20mM), Indirubin - 3 Monooxime (1 microM) and 3-(2, 4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione (SB216763) (3 microM), was not attenuated. This differential attenuation by hyperlipidaemia, of IPC and pharmacological preconditioning induced cardioprotection is a new finding in our study. GSK-3beta inhibition is reported to increase the threshold of opening for MPTP during reperfusion. Administration of atractyloside (20 microM), an opener of MPTP, significantly attenuated the Cardioprotective Effect of IPC in normal heart, and pharmacological preconditioning in the hyperlipidaemic rat heart. Thus, the attenuation of Cardioprotective Effect of IPC in hyperlipidaemic heart may be due to inhibition of protective signaling pathways upstream of GSK-3beta and inhibition of opening of MPTP.

  • Involvement of GSK-3β in attenuation of the Cardioprotective Effect of ischemic preconditioning in diabetic rat heart.
    Molecular and cellular biochemistry, 2010
    Co-Authors: Harlokesh Narayan Yadav, Manjeet Singh, Pyare Lal Sharma
    Abstract:

    Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthase kinase-3β (GSK-3β) that inhibits the opening of mitochondrial permeability transition pore (MPTP). The activity of glycogen GSK-3β is elevated during diabetes mellitus (DM). This study investigated the role of GSK-3β in attenuation of Cardioprotective Effect of IPC in diabetic rat. DM was induced by single administration of streptozotocin (STZ, 50 mg/kg, i.p.). Isolated perfused heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed in coronary effluent. IPC significantly decreased myocardial infarct size and release of LDH and CK-MB from normal rat heart. The Cardioprotective Effect of IPC was significantly attenuated in diabetic rat. Four episodes of preconditioning by either of GSK-3β inhibitors, lithium chloride (LiCl, 20 mM), indirubin-3 monooxime (1 μM), and SB216763 (3 μM) significantly reduced the LDH and CK-MB release and decreased infarct size in diabetic rat heart. Perfusion of atractyloside, an opener of MPTP, significantly attenuated, the Cardioprotective Effect of IPC in normal rat heart, and of GSK-3β inhibitor induced preconditioning in the DM rat heart. Our results suggest that preconditioning with GSK-3β inhibitors in diabetic rat heart may provide a more consistent cardioprotection, as compared to IPC. Also, the mechanism of diabetes mellitus-induced attenuation of Cardioprotective Effect of IPC involves activation of GSK-3β, due to impaired protective upstream signaling pathways and opening of MPTP during reperfusion.

  • Mechanism of Cardioprotective Effect of erythropoietin-induced preconditioning in rat heart.
    Indian journal of pharmacology, 2010
    Co-Authors: Kavita Garg, Manjeet Singh, Harlokesh Narayan Yadav, Pyare Lal Sharma
    Abstract:

    Objective : The Cardioprotective potential of human recombinant erythropoietin (alpha) (Epo) against ischemia-reperfusion-induced injury is well known. But, the underlying mechanisms are not well elucidated. The aim of this study was to characterize the mechanism involved in the Cardioprotective Effect of Epo-induced preconditioning in isolated rat heart. Materials and Methods : The heart was mounted on a Langendorff apparatus. After 10 min of stabilization, four cycles of ischemic preconditioning (IPC) were given followed by 30 min of global ischemia and 120 min of reperfusion. Epo preconditioning was induced by four cycles of 5-min perfusion of K-H solution containing Epo (1.0 U/ml) followed by 5 min perfusion with K-H solution. Myocardial infarct size was estimated macroscopically using the triphenyltetrazolium chloride staining technique. The extent of myocardial injury was measured by release of lactate dehydrogenase and creatine kinase-MB in the coronary effluent. Results : The present study demonstrates that Epo preconditioning was almost as Effective as IPC. Administration of Wortmannin (100 nM), a PI-3K inhibitor, or Chelerythrine (1 μM), a protein kinase-C (PKC) inhibitor, or AG490 (5 μM), a JAK-2 inhibitor, significantly attenuated the Cardioprotective Effects of Epo-induced preconditioning. Conclusion : Our result suggest that the Cardioprotective potential of Epo-induced preconditioning in isolated rat heart was due to an interplay of the JAK-2, PI-3K and PKC pathways. Inhibition of any one of the three pathways was sufficient to block the Cardioprotective Effect of Epo-induced preconditioning in isolated rat heart.

  • Mechanism of Cardioprotective Effect of Remote Aortic Preconditioning
    Pathophysiology of Cardiovascular Disease, 2004
    Co-Authors: Manjeet Singh, Ajay Sharma
    Abstract:

    The present study is designed to investigate the mechanism of Cardioprotective Effect of remote aortic preconditioning. Four episodes, each episode comprising of 5min aortic occlusion followed by reperfusion for 5min were employed to produce remote preconditioning. Heart was isolated, perfused on Langendorff’s apparatus and subjected to 30 min of sustained global ischaemia followed by reperfusion for 120min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Remote aortic preconditioning reduced release of LDH and CK in coronary effluent and decreased myocardial infarct size. Reserpine, a biogenic amine depletor, ruthenium red, a sarcoplasmic reticulum Ca2+ channel blocker, ethylisopropylamiloride, (EIPA) a Na+/H+ exchange inhibitor and gadolinium, a mechanosensitive channel blocker, did not modulate the Cardioprotective Effect of remote aortic preconditioning. On the other hand, verapamil, a L type Ca2+ channel blocker, and 2′,4′-dichlorobenzamil, a Na+/Ca2+ exchange inhibitor, attenuated the Cardioprotective Effect of remote aortic preconditioning. On the basis of these results, it may be suggested that the Cardioprotective Effect of remote aortic preconditioning may be mediated through opening of L-type Ca2+ channels or activation of Na+/ Ca2+ exchange.

  • Protein kinase C activation and Cardioprotective Effect of preconditioning with oxidative stress in isolated rat heart
    Molecular and Cellular Biochemistry, 2001
    Co-Authors: Ajay Sharma, Manjeet Singh
    Abstract:

    The present study is designed to investigate the Effect of myocardial preconditioning with oxidative stress induced by pyrogallol or H_2O_2, on ischaemia-reperfusion induced myocardial injuiry. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Four episodes of preconditioning induced by pyrogallol or hydrogen peroxide (H_2O_2) or ischaemia markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. Administration of polymyxin B, a protein kinase C (PKC) inhibitor, during pyrogallol, H_2O_2 or ischaemic preconditioning markedly attenuated the Cardioprotective Effect of preconditioning produced with oxidative stress or ischaemia. These results suggest that preconditioning with oxidative stress may provide cardioprotection similar to ischaemic preconditioning, against ischaemia-reperfusion injury and this Cardioprotective Effect may be mediated through activation of PKC.

Ajay Sharma - One of the best experts on this subject based on the ideXlab platform.

  • Mechanism of Cardioprotective Effect of Remote Aortic Preconditioning
    Pathophysiology of Cardiovascular Disease, 2004
    Co-Authors: Manjeet Singh, Ajay Sharma
    Abstract:

    The present study is designed to investigate the mechanism of Cardioprotective Effect of remote aortic preconditioning. Four episodes, each episode comprising of 5min aortic occlusion followed by reperfusion for 5min were employed to produce remote preconditioning. Heart was isolated, perfused on Langendorff’s apparatus and subjected to 30 min of sustained global ischaemia followed by reperfusion for 120min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Remote aortic preconditioning reduced release of LDH and CK in coronary effluent and decreased myocardial infarct size. Reserpine, a biogenic amine depletor, ruthenium red, a sarcoplasmic reticulum Ca2+ channel blocker, ethylisopropylamiloride, (EIPA) a Na+/H+ exchange inhibitor and gadolinium, a mechanosensitive channel blocker, did not modulate the Cardioprotective Effect of remote aortic preconditioning. On the other hand, verapamil, a L type Ca2+ channel blocker, and 2′,4′-dichlorobenzamil, a Na+/Ca2+ exchange inhibitor, attenuated the Cardioprotective Effect of remote aortic preconditioning. On the basis of these results, it may be suggested that the Cardioprotective Effect of remote aortic preconditioning may be mediated through opening of L-type Ca2+ channels or activation of Na+/ Ca2+ exchange.

  • Protein kinase C activation and Cardioprotective Effect of preconditioning with oxidative stress in isolated rat heart
    Molecular and Cellular Biochemistry, 2001
    Co-Authors: Ajay Sharma, Manjeet Singh
    Abstract:

    The present study is designed to investigate the Effect of myocardial preconditioning with oxidative stress induced by pyrogallol or H_2O_2, on ischaemia-reperfusion induced myocardial injuiry. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Four episodes of preconditioning induced by pyrogallol or hydrogen peroxide (H_2O_2) or ischaemia markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. Administration of polymyxin B, a protein kinase C (PKC) inhibitor, during pyrogallol, H_2O_2 or ischaemic preconditioning markedly attenuated the Cardioprotective Effect of preconditioning produced with oxidative stress or ischaemia. These results suggest that preconditioning with oxidative stress may provide cardioprotection similar to ischaemic preconditioning, against ischaemia-reperfusion injury and this Cardioprotective Effect may be mediated through activation of PKC.

  • Possible mechanism of Cardioprotective Effect of angiotensin preconditioning in isolated rat heart.
    European journal of pharmacology, 2000
    Co-Authors: Ajay Sharma, Manjeet Singh
    Abstract:

    Abstract The present study is designed to investigate the mechanism of Cardioprotective Effect of angiotensin II preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for lactate dehydrogenase and creatine kinase enzyme release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using triphenyltetrazolium chloride staining. Four episodes of angiotensin II preconditioning markedly reduced lactate dehydrogenase and creatine kinase release in the coronary effluent and decreased myocardial infarct size. Administration of prazosin (α1-adrenoceptor antagonist) before global ischaemia reduced the extent of ischaemia–reperfusion-induced myocardial injury. Moreover, administration of prazosin during angiotensin II preconditioning or depletion of biogenic amines by reserpinisation (0.5 mg/kg i.p.) did not affect the Cardioprotective Effect of angiotensin II preconditioning. On the other hand, colchicine (5 mg/kg i.p.) or polymyxin B (50 μM) treatment markedly attenuated the Cardioprotective Effect of angiotensin II preconditioning. On the basis of these results, it may be concluded that the Cardioprotective Effects of angiotensin II preconditioning may be mediated through protein kinase C and may not involve release of norepinephrine or activation of α1-adrenoceptor.

  • Possible mechanism of Cardioprotective Effect of ischaemic preconditioning in isolated rat heart.
    Pharmacological research, 2000
    Co-Authors: Ajay Sharma, Manjeet Singh
    Abstract:

    The present study is designed to investigate the mechanism of the Cardioprotective Effect of ischaemic preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Four episodes of ischaemic preconditioning markedly reduced LDH and CK release in the coronary effluent and decreased myocardial infarct size. Administration of prazosin (alpha(1)adrenoceptor antagonist) before global ischaemia reduced the extent of ischaemia-reperfusion induced myocardial injury. The Cardioprotective Effect of ischaemic preconditioning was abolished by prazosin and colchicine (microtubule disaggregator). On the basis of these results, it may be concluded that the Cardioprotective Effects of ischaemic preconditioning may be mediated through stimulation of alpha(1)adrenoceptors and translocation of PKC.

  • Effect of actinomycin D and cycloheximide on ischemic preconditioning-induced delayed Cardioprotective Effect in rats.
    Indian journal of experimental biology, 2000
    Co-Authors: Devinder Singh, Ajay Sharma, Manjeet Singh
    Abstract:

    The present study was designed to investigate the Effect of actinomycin D, a transcription inhibitor, and cycloheximide, a translation inhibitor, on the delayed Cardioprotective Effect of ischemic preconditioning. Left thoracotomy was performed in anaesthetized rats at 4th/5th intercostal space and polypropylene suture (5-0) was employed to occlude left common coronary artery. Ischemic preconditioning was produced by four episodes of 5 min of coronary artery occlusion followed by 5 min of reperfusion and thoracic cavity was sutured. Left thoracotomy was performed again after 24 hr of ischemic preconditioning and left coronary artery was occluded for 30 min followed by reperfusion for 120 min. Area at risk and infarct size was estimated by patent blue and TTC staining respectively. Total left ventricular RNA was isolated and estimated quantitatively. Ischemic preconditioning, 24 hr after its induction, produced significant decrease in myocardial infarct size occurred as a result of sustained ischemia and reperfusion but produced no marked Effect on ventricular RNA content. Actinomycin D and cycloheximide only, in high dose, markedly attenuated ischemic preconditioning induced decrease in myocardial infarct size. However, no such Effect was noted with low dose of cycloheximide. The results suggest that delayed Cardioprotective Effect of ischemic preconditioning may be mediated through denovo synthesis of protein(s) which is regulated both at transcriptional and translational level.

Vinay Parikh - One of the best experts on this subject based on the ideXlab platform.

Shigehito Sato - One of the best experts on this subject based on the ideXlab platform.

  • Cardioprotective Effect of therapeutic hypothermia at 34 c against ischaemia reperfusion injury mediated by pi3k and nitric oxide in a rat isolated heart model
    Resuscitation, 2012
    Co-Authors: Toshiaki Mochizuki, Takasumi Katoh, Katsunori Aoki, Shigehito Sato
    Abstract:

    Abstract Aim Therapeutic hypothermia (TH) is widely used as a Cardioprotective treatment for cardiac arrest. TH at 30–32°C during ischaemia and reperfusion has a Cardioprotective Effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a Cardioprotective Effect and to determine if this Effect is mediated by nitric oxide (NO) and phosphatidylinositol 3′-kinase (PI3K). Methods Langendorff perfusion of Sprague–Dawley rat hearts was initiated at 75mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n =7): control group; ischaemia group, with 34°C TH during ischaemia for 30min and reperfusion for 180min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound. Results TH reduced the left ventricle infarct size from 54.2±14.8% of the control group to 11.9±6.3% (ischaemia group, p p p =0.009), 40.9±4.1% ( p =0.021), and 51.9±13.0% ( p Conclusions TH of 34°C showed a Cardioprotective Effect even with late initiation of cooling during reperfusion. The Effect was mediated by NO and PI3K.

  • Cardioprotective Effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model.
    Resuscitation, 2011
    Co-Authors: Toshiaki Mochizuki, Takasumi Katoh, Katsunori Aoki, Shigehito Sato
    Abstract:

    Abstract Aim Therapeutic hypothermia (TH) is widely used as a Cardioprotective treatment for cardiac arrest. TH at 30–32°C during ischaemia and reperfusion has a Cardioprotective Effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a Cardioprotective Effect and to determine if this Effect is mediated by nitric oxide (NO) and phosphatidylinositol 3′-kinase (PI3K). Methods Langendorff perfusion of Sprague–Dawley rat hearts was initiated at 75mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n =7): control group; ischaemia group, with 34°C TH during ischaemia for 30min and reperfusion for 180min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound. Results TH reduced the left ventricle infarct size from 54.2±14.8% of the control group to 11.9±6.3% (ischaemia group, p p p =0.009), 40.9±4.1% ( p =0.021), and 51.9±13.0% ( p Conclusions TH of 34°C showed a Cardioprotective Effect even with late initiation of cooling during reperfusion. The Effect was mediated by NO and PI3K.

  • The Cardioprotective Effect of dexmedetomidine on global ischaemia in isolated rat hearts.
    Resuscitation, 2007
    Co-Authors: Hisako Okada, Tadayoshi Kurita, Toshiaki Mochizuki, Koji Morita, Shigehito Sato
    Abstract:

    Summary Aim Dexmedetomidine is a highly specific and selective α-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. Methods Isolated rat hearts were subjected to 30 min of global ischaemia followed by 120 min reperfusion, with administration of 0, 1 and 10 nM dexmedetomidine during the pre-ischaemic period ( n  = 7 each group). Secondly, 1 μM yohimbine, an α-2 antagonist, was given during the pre-ischaemic period, alone or in combination with 10 nM dexmedetomidine ( n  = 7 each group). Results 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 10 nM dexmedetomidine, respectively), which was also reversed by yohimbine (43.6 ± 1.4%). Conclusion Dexmedetomidine exhibited a Cardioprotective Effect on global ischaemia in the isolated rat heart model, which was mediated by α-2 adrenergic stimulation.

Toshiaki Mochizuki - One of the best experts on this subject based on the ideXlab platform.

  • Cardioprotective Effect of therapeutic hypothermia at 34 c against ischaemia reperfusion injury mediated by pi3k and nitric oxide in a rat isolated heart model
    Resuscitation, 2012
    Co-Authors: Toshiaki Mochizuki, Takasumi Katoh, Katsunori Aoki, Shigehito Sato
    Abstract:

    Abstract Aim Therapeutic hypothermia (TH) is widely used as a Cardioprotective treatment for cardiac arrest. TH at 30–32°C during ischaemia and reperfusion has a Cardioprotective Effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a Cardioprotective Effect and to determine if this Effect is mediated by nitric oxide (NO) and phosphatidylinositol 3′-kinase (PI3K). Methods Langendorff perfusion of Sprague–Dawley rat hearts was initiated at 75mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n =7): control group; ischaemia group, with 34°C TH during ischaemia for 30min and reperfusion for 180min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound. Results TH reduced the left ventricle infarct size from 54.2±14.8% of the control group to 11.9±6.3% (ischaemia group, p p p =0.009), 40.9±4.1% ( p =0.021), and 51.9±13.0% ( p Conclusions TH of 34°C showed a Cardioprotective Effect even with late initiation of cooling during reperfusion. The Effect was mediated by NO and PI3K.

  • Cardioprotective Effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model.
    Resuscitation, 2011
    Co-Authors: Toshiaki Mochizuki, Takasumi Katoh, Katsunori Aoki, Shigehito Sato
    Abstract:

    Abstract Aim Therapeutic hypothermia (TH) is widely used as a Cardioprotective treatment for cardiac arrest. TH at 30–32°C during ischaemia and reperfusion has a Cardioprotective Effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a Cardioprotective Effect and to determine if this Effect is mediated by nitric oxide (NO) and phosphatidylinositol 3′-kinase (PI3K). Methods Langendorff perfusion of Sprague–Dawley rat hearts was initiated at 75mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n =7): control group; ischaemia group, with 34°C TH during ischaemia for 30min and reperfusion for 180min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound. Results TH reduced the left ventricle infarct size from 54.2±14.8% of the control group to 11.9±6.3% (ischaemia group, p p p =0.009), 40.9±4.1% ( p =0.021), and 51.9±13.0% ( p Conclusions TH of 34°C showed a Cardioprotective Effect even with late initiation of cooling during reperfusion. The Effect was mediated by NO and PI3K.

  • The Cardioprotective Effect of dexmedetomidine on global ischaemia in isolated rat hearts.
    Resuscitation, 2007
    Co-Authors: Hisako Okada, Tadayoshi Kurita, Toshiaki Mochizuki, Koji Morita, Shigehito Sato
    Abstract:

    Summary Aim Dexmedetomidine is a highly specific and selective α-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. Methods Isolated rat hearts were subjected to 30 min of global ischaemia followed by 120 min reperfusion, with administration of 0, 1 and 10 nM dexmedetomidine during the pre-ischaemic period ( n  = 7 each group). Secondly, 1 μM yohimbine, an α-2 antagonist, was given during the pre-ischaemic period, alone or in combination with 10 nM dexmedetomidine ( n  = 7 each group). Results 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 10 nM dexmedetomidine, respectively), which was also reversed by yohimbine (43.6 ± 1.4%). Conclusion Dexmedetomidine exhibited a Cardioprotective Effect on global ischaemia in the isolated rat heart model, which was mediated by α-2 adrenergic stimulation.