Opioid receptor agonist reduces myocardial ischemic injury when administered during early phase of myocardial ischemia

Yi, Shuhua; Sun, Shijie; Yang, Xianghong; Weil, Max Harry; Tang, Wanchun

doi:10.1016/j.resuscitation.2010.02.014

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…Many reports suggested that pentazocine shows cardioprotective effects in human in the early phase after cardiac surgery or isolated ischemic heart (3,21,27,33). However, it is unclear whether chronic pentazocine treatment inhibits heart failure following PO-induced hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

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Diverse regulation of IP₃ and ryanodine receptors by pentazocine through σ₁-receptor in cardiomyocytes

Tagashira

Bhuiyan

Fukunaga

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Although pentazocine binds to σ1-receptor (σ1R) with high affinity, the physiological relevance of its binding remains unclear. We first confirmed that σ1R stimulation with pentazocine rescues contractile dysfunction following pressure overload (PO)-induced cardiac hypertrophy ovariectomized (OVX) female rats. In in vivo studies, vehicle, pentazocine (0.5-1.0 mg/kg ip), and NE-100 (1.0 mg/kg po), a σ1R antagonist, were administered for 4 wk (once daily) starting from the onset of aortic banding after OVX. We also examined antihypertrophic effects of pentazocine (0.5-1 μM) in cultured cardiomyocytes exposed to angiotensin II. Pentazocine administration significantly inhibited PO-induced cardiac hypertrophy and rescued hypertrophy-induced impairment of cardiac dysfunctions such as left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contraction and relaxation (±dp/dt) rates. Coadministration of NE-100 with pentazocine eliminated pentazocine-induced amelioration of heart dysfunction. Interestingly, pentazocine administration inhibited PO-induced σ1R reduction and inositol-1,4,5-trisphosphate (IP3) receptor type 2 (IP3R2) upregulation in heart. Therefore, the reduced mitochondrial ATP production following PO was restored by pentazocine administration. Furthermore, we found that σ1R binds to the ryanodine receptor (RyR) in addition to IP3 receptor (IP3R) in cardiomyocytes. The σ1R/RyR complexes were decreased following OVX-PO and restored by pentazocine administration. We noticed that pentazocine inhibits the ryanodine-induced Ca(2+) release from sarcoplasmic reticulum (SR) in cultured cardiomyocytes. Taken together, the stimulation of σ1R by pentazocine rescues cardiac dysfunction by restoring IP3R-mediated mitochondrial ATP production and by suppressing RyR-mediated Ca(2+) leak from SR in cardiomyocytes.

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Section: Discussionmentioning

confidence: 99%

“…The increase in contraction amplitude is transient (23). The ameliorated effect of pentazocine after cardiac ischemia is reported in the Langendorff-perfused isolated heart preparation (27). Moreover, pentazocine shows cardioprotective effects in human or rodents after cardiac surgery (3,14,21,33).…”

mentioning

confidence: 95%

Diverse regulation of IP₃ and ryanodine receptors by pentazocine through σ₁-receptor in cardiomyocytes

Tagashira

Bhuiyan

Fukunaga

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…These authors also did not test any OR antagonist. It should be noted that some investigators did not find a positive effect of morphine or U50,488 on cardiac contractility although they did decrease infarct size …”

Section: Effect Of Opioids On Recovery Of Cardiac Contractility Durinmentioning

confidence: 95%

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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“…␦-Opioids agonists Animals/rat-heart model Reduction of myocardial metabolism during ischaemia, amelioration of myocardial dysfunction and increased survival post-ROSC. [56][57][58] Thombolysis Humans No treatment benefit from routine use in OHCA patients. May be useful in selected patients with STEMI and pulmonary embolism [61][62][63] Neurotensin Animals Prolonged decrease of body temperature.…”

Section: Humans Nrtsmentioning

confidence: 99%

“…In an isolated rat-heart model pentazocine was more effective in preventing myocardial dysfunction when administered before CA rather than during the reperfusion period. 57 The synthetic ␦-opioid receptor agonist d-Ala (2)-d-Leu (5) enkephalin (DADLE), has also been tested in CA. 58 In an isolated working rat-heart model, pharmacological activation of delta-opioid receptors using DADLE offered myocardial protection similar to that conferred by ischaemic preconditioning.…”

Section: ␦-Opioid Agonistsmentioning

confidence: 99%

Emerging pharmaceutical therapies in cardiopulmonary resuscitation and post-resuscitation syndrome

Charalampopoulos

Νικολάου

2011

Resuscitation

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Opioid receptor agonist reduces myocardial ischemic injury when administered during early phase of myocardial ischemia

Cited by 7 publications

References 37 publications

Diverse regulation of IP₃ and ryanodine receptors by pentazocine through σ₁-receptor in cardiomyocytes

Diverse regulation of IP₃ and ryanodine receptors by pentazocine through σ₁-receptor in cardiomyocytes

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

Emerging pharmaceutical therapies in cardiopulmonary resuscitation and post-resuscitation syndrome

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Opioid receptor agonist reduces myocardial ischemic injury when administered during early phase of myocardial ischemia

Cited by 7 publications

References 37 publications

Diverse regulation of IP3 and ryanodine receptors by pentazocine through σ1-receptor in cardiomyocytes

Diverse regulation of IP3 and ryanodine receptors by pentazocine through σ1-receptor in cardiomyocytes

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

Emerging pharmaceutical therapies in cardiopulmonary resuscitation and post-resuscitation syndrome

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Product

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Diverse regulation of IP₃ and ryanodine receptors by pentazocine through σ₁-receptor in cardiomyocytes

Diverse regulation of IP₃ and ryanodine receptors by pentazocine through σ₁-receptor in cardiomyocytes