Effects of selective receptor agonists and antagonists during myocardial ischaemia

McIntosh, Marie; Kane, Kathleen A.; Parratt, J. R.

doi:10.1016/0014-2999(92)90649-o

Cited by 24 publications

(4 citation statements)

References 24 publications

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“…Opioids have been found to have minimal effect on coronary vessel vasomotor tone. Studies on the influence of opioids on perioperative ischemia have suggested that they can mimic ischemic preconditioning, reducing infarct size . There may be multiple mechanisms involved, perhaps via a reduction in oxidant stress on cardio‐myocytes or facilitated via the adenosine A1 receptor or protein kinase C .…”

Section: Introductionmentioning

confidence: 99%

Cardiac Effects of Opioid Therapy

2015

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There are limited data to suggest that chronic opioid administration may be associated with an increased risk for cardiac-related adverse effects. However, this observation has not yet been confirmed. Regardless, while opioids are an important medication for the treatment of a multitude of chronic pain conditions, careful patient selection, and diligent monitoring is likely to decrease the risk of harm and improve patient outcomes.

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Section: Introductionmentioning

confidence: 99%

Cardiac Effects of Opioid Therapy

2015

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“…These data were confirmed by Parratt's group who carried out experiments with rats. 25,27 In 1992, Lee 28 showed that in dogs with coronary artery ligation and reperfusion, only (-)-naloxone exhibited antiarrhythmic properties, but its nonactive stereoisomer (+)-naloxone had no effect on the arrhythmogenic effects of ischemia and reperfusion. In 1999, it was reported that methylnaltrexone produced an antiarrhythmic effect in rabbits with coronary artery occlusion.…”

Section: Discussionmentioning

confidence: 99%

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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“…κ‐Opioid receptors have been shown to exist in the heart by receptor binding assay (Ventura et al , 1989; Tai et al , 1991) and physiological studies (Tai et al , 1992; Ventura et al , 1992). Accumulating evidence suggests that stimulation of cardiac opioid receptors may contribute to arrhythmias induced by myocardial ischaemia‐reperfusion (Lee & Wong, 1986; Machuganska et al , 1987; Boachie‐Ansah et al , 1989; McIntosh et al , 1992) and that the κ‐receptor is the most likely opioid receptor subtype involved (Sitsapesan & Parratt, 1989; Wong et al , 1990). Previous studies have shown that cardiac κ‐receptor stimulation increases the formation of inositol (1,4,5)‐trisphosphate (IP 3 ), which mobilizes Ca 2± from the intracellular stores, leading to an increase in intracellular free calcium ([Ca 2± ] i ) (Ventura et al , 1992; Wong et al , 1995).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of [³H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

Zhang

Wang

Xia

et al. 1997

British J Pharmacology

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The calcium channel blockers (CCBs), nifedipine, nicardipine, diltiazem and verapamil, were used to displace the binding of [3H]‐U69593 ((5a,7a,8b)‐(+)‐N‐methyl‐N‐(7‐[1‐pyrrolidinyl]‐1‐oxaspiro[4,5]dec‐8‐yl)‐benzeneacetamide), a specific κ‐opioid agonist, in the rat cardiac sarcolemma. The CCBs competed with the binding of [3H]‐U69593 (4 nm) in a dose‐dependent manner. The displacing potency of verapamil was 55 times greater than that of nifedipine. The effects of two CCBs, verapamil and nifedipine, on the arrhythmogenic action of κ‐receptor stimulation by a specific κ‐receptor agonist, U50,488H (trans‐(±‐3,4‐dichloro‐N‐methyl‐N‐(2‐[1‐pyrrolidinyl] cyclohexyl) benzeacetamide methanesulphonate), were also studied in the rat isolated perfused heart. U50,488H 80–800 nmol dose‐dependently induced arrhythmias, which were completely abolished by a selective κ‐receptor antagonist, nor‐BNI (nor‐binaltorphimine,17,17′‐(dicyclopropylmethyl)‐6,6′,7,7′‐6,6′‐imino‐7,7′‐binorphinan‐3,4′,14, 14′‐tetrol), at 100 nmol. The arrhythmogenic effect was also attenuated by both verapamil and nifedipine in a dose‐dependent manner. The ED50 values for verapamil and nifedipine were 2.75 and 63.7 nmol, respectively. The antiarrhythmic potencies of these two CCBs were correlated to their displacing potencies and inversely related to their well known potencies in inhibiting transmembrane Ca2+ influx in the cardiac muscle. Measurement of [Ca2+]i in the absence of free extracellular Ca2+ by a spectrofluorometric method, with fura‐2 as Ca2+ indicator, showed that U50,488H 5×10−5 m slowly increased [Ca2+]i in single ventricular myocytes and this effect was abolished by pretreatment with nor‐BNI (5 μm), or ryanodine (5 μm). Verapamil 1 and 10 μm abolished the effect of U50,488H in 37.5% (3 out of 8) and 100% (12 out of 12) of the cells studied, respectively. On the other hand, nifedipine 10 and 100 μm had no effect at all. Neither verapamil nor nifedipine exerted any significant effect on the caffeine‐induced Ca2+ transient. The observations suggest that CCBs may inhibit the actions of κ‐receptor stimulation at the level of the κ‐receptor. British Journal of Pharmacology (1997) 120, 827–832; doi:

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Effects of selective receptor agonists and antagonists during myocardial ischaemia

Cited by 24 publications

References 24 publications

Cardiac Effects of Opioid Therapy

Cardiac Effects of Opioid Therapy

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

Inhibition of [³H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

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Effects of selective receptor agonists and antagonists during myocardial ischaemia

Cited by 24 publications

References 24 publications

Cardiac Effects of Opioid Therapy

Cardiac Effects of Opioid Therapy

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

Inhibition of [3H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

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Inhibition of [³H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart