Contribution of the Endogenous Opioid System to Regulation of Heart Resistance to the Arrhythmogenic Effect of Short-term Ischemia and Reperfusion

Maslov, L. N.; Liishmanov, A Iu; Budankova, E. V.; Stakheev, Dmitry; Solenkova, Nataliya V.; Barzakh, E. I.; Oeltgen, Peter R.; Gross, Garrett J.; Chang, Wei-Chun

doi:10.1007/s10525-005-0115-1

Cited by 3 publications

(7 citation statements)

References 25 publications

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“…The selective δ 1 -OR antagonist, BNTX (7-benzylidenenaltrexone maleate), was given at a dose of 0.7 mg/kg (Maslov et al, 2009;Sofuoglu et al, 1993), and the selective δ 2 -OR antagonist, naltriben mesylate, was used at a dose of 0.3 mg/kg (Maslov et al, 2009;Kamei et al, 1995). The selective κ-OR antagonist, nor-binaltorphimine (nor-BNI), was administered at a dose 9 mg/kg (Birch et al, 1987;Maslov et al, 2005aMaslov et al, , 2005b. The selective μ-OR inhibitor, CTAP (NH 2 -D-Phe-c[Cys-Tyr-D-Trp-Arg-Thr-L-Pen]-Thr-NH 2 ), was used at a dose of 0.1 mg/kg based on our preliminary experiments.…”

Section: Opioid Receptor Antagonistsmentioning

confidence: 99%

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Maslov¹,

Нарыжная²,

Tsibulnikov³

et al. 2013

Life Sciences

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Section: Opioid Receptor Antagonistsmentioning

confidence: 99%

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Maslov¹,

Нарыжная²,

Tsibulnikov³

et al. 2013

Life Sciences

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“…This agrees with previously published results of our investigations, which showed that opioid receptor antagonists had no effect on the incidence of occlusion and reperfusion-induced arrhythmias in rats. 12 This fact indicates that endogenous opioids do not regulate cardiac tolerance to the arrhythmogenic effects of ischemia and reperfusion in nonadapted rats. However, our data contradict the results of other investigators who found antiarrhythmic effects of opioid receptor antagonists during cardiac ischemia and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that all above-mentioned investigators performed their experiments with animals anesthetized with barbiturates, while we used chloralose or ketamine as anesthetics. 12 It should be noted that cardiovascular system response to IV-administered enkephalins is directly opposite in dogs anesthetized with barbiturates and chloralose. 30 Perhaps opioid receptor antagonists exhibited antiarrhythmic properties only in animals anesthetized with barbiturates but not chloralose or ketamine.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, our previous studies have shown that delta opioids are antiarrhythmic in the setting of cardiac ischemia reperfusion 10,12 and counteract the hypotensive effects of hemorrhagic shock. 38,39 In addition, long-term opioid use, while not without side effects, is more easily tolerated than long-term amiodarone therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Cannula placement, arterial blood gas monitoring, and body temperature maintenance, as well as coronary artery occlusion, ischemia, production, and reperfusion in the intact ischemic rat heart model have been previously described by Maslov et al 10,12 Study Protocol Experiment 1: The Effects of Mu and Delta Opioid Receptor Agonists and Nociceptin on the Incidence of Ventricular Arrhythmias During 45 Minutes of Ischemia and 2 Hours of Reperfusion. The choice of doses of opioid receptor ligands was guided by results from our prior experiments in which we assessed left ventricular infarct volume of rats infused with l, d, and j opioid receptor agonists that had been subjected to 45 minutes of ischemia and 2 hours of reperfusion.…”

Section: Animal Subjects and Preparationmentioning

confidence: 99%

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Activation of Peripheral Delta Opioid Receptors Increases Cardiac Tolerance to Arrhythmogenic Effect of Ischemia/Reperfusion

Maslov

Oeltgen

Lishmanov

et al. 2014

Academic Emergency Medicine

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Objectives: The objective of this study was to investigate the role of peripheral l, d 1 , d 2 , and nociceptin opioid receptors agonists in the regulation of cardiac tolerance to the arrhythmogenic effect of ischemia/ reperfusion in rats.Methods: Anesthetized open-chest male Wistar rats were subjected to either 45 minutes of left coronary artery occlusion (phase 1a 10 minutes and phase 2b 35 minutes) and 2 hours of reperfusion in Experiment 1 or 10 minutes of ischemia and 10 minutes of reperfusion in Experiment 2. In Experiment 1, saline or vehicle controls and the mu-specific opioids dermorphin-H (Derm-H) and ([D-Ala2, N-Me-Phe4, Gly-ol5] enkephalin (DAMAGO); the delta-1-specific opioid D-Pen2,5enkephalin (DPDPE); nociceptin; and the delta-2-specific opioids deltorphin-II (Delt-II), Delt-Dvariant (Delt-Dvar), and deltorphin-E (Delt-E) were infused 15 minutes prior to ischemia. In Experiment 2, DPDPE, Delt-D, Delt-Dvar, and Delt-E were infused at 15 minutes prior to ischemia. The universal opioid receptor antagonist naltrexone, the peripherally acting antagonist naloxone methiodide, the selective d 1 antagonist 7-benzylidene naltrexone maleate, and the specific d 2 antagonist naltriben mesylate were infused 25 minutes prior to ischemia.Results: In Experiment 1, pretreatment with the l opioids Derm-H and DAMGO, DPDPE, and nociceptin at all doses tested did not reduce the incidence of ischemia-induced arrhythmias compared to controls during 45 minutes of ischemia. The d 2 opioids Delt-II (0.12 mg/kg), Delt-Dvar (0.3 mg/kg), and Delt-E (0.18 mg/kg) all demonstrated significant antiarrhythmic effects at the 150 nmol/kg dose compared to saline or vehicle controls. Nine of 19 animals treated with Delt-II were tolerant without ventricular arrhythmias to the arrhythmogenic effect of ischemia during the first 10 minutes of ischemia (phase 1a) and 11 of 19 were without ventricular arrhythmias during the following 35 minutes of ischemia (phase 1b). Delt-II also decreased the incidence of premature ventricular contractions and ventricular tachycardia by almost half during phase 1a. Delt-II did not affect the incidence of ventricular fibrillation (VF). Pretreatment with DeltDvar and Delt-E completely blocked the incidence of VF in phase 1b. Delt-E also decreased premature ventricular contractions by 50%, and the incidence of ventricular tachycardia decreased over twofold in phase 1b of ischemia. There was no enhanced tolerance by any of the delta-2 opioids to the arrhythmogenic effect of reperfusion after long-term ischemia. In Experiment 2, after 10 minutes of ischemia and 10 minutes of reperfusion, Delt-II (0.12 mg/kg) reduced the incidence of premature ventricular contractions and ventricular tachycardia compared to controls, and completely blocked the incidence of VF following 10 minutes of reperfusion. Delt-Dvar and Delt-E were without effect, as was DPDPE following 10 minutes of reperfusion. The antiarrhythmic effect of Delt-II during 10 minutes of ischemia and 10 minutes of reperfusion was completely blocked ...

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Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

Maslov

Khaliulin

Oeltgen

et al. 2016

Medicinal Research Reviews

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It has now been demonstrated that the μ, δ1, δ2, and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias.

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Contribution of the Endogenous Opioid System to Regulation of Heart Resistance to the Arrhythmogenic Effect of Short-term Ischemia and Reperfusion

Cited by 3 publications

References 25 publications

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Activation of Peripheral Delta Opioid Receptors Increases Cardiac Tolerance to Arrhythmogenic Effect of Ischemia/Reperfusion

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

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