Extension of tissue survival time in multiorgan block preparation with a delta opioid DADLE ([D-Ala2,D-Leu5]-enkephalin)

Chien, Sufan; Oeltgen, Peter R.; Diana, John N.; Salley, Robert K.; Su, Tsung‐Ping

doi:10.1016/s0022-5223(94)70370-1

Cited by 72 publications

(28 citation statements)

References 6 publications

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“…Studies implicate an opioid‐like agent in this powerful adaptation, the levels of which increase in hibernation to induce beneficial effects in a DOR‐dependent manner, including myocardial tolerance to injurious insult (Bruce et al ., ; Bolling et al ., ; Kevelaitis et al ., ). Treatment with exogenous DOR‐selective opioids can also induce hibernation states in multiple species, and enhance organ stress resistance (Oeltgen et al ., ; Chien et al ., ). As with cardiac protection via opioid receptor agonists and opioid receptor‐dependent ischaemic preconditioning, the beneficial effects of hibernation involve activation of ATP‐sensitive K + (K ATP ) channels (Kevelaitis et al ., ).…”

Section: The Opioid Receptor System Orchestrates Cellular To Organismmentioning

confidence: 97%

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Headrick

Hoe

Toit

et al. 2015

British J Pharmacology

134

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Ischaemic heart disease (IHD) remains a major cause of morbidity/mortality globally, firmly established in Westernized or 'developed' countries and rising in prevalence in developing nations. Thus, cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, is a very important, although still elusive, clinical goal. The opioid receptor system, encompassing the δ (vas deferens), κ (ketocyclazocine) and μ (morphine) opioid receptors and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears as a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central opioid receptor signalling may also enhance the ability of the heart to withstand I-R injury. The δ-and κ-opioid receptors are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for μ opioid receptor-dependent protection in animal and human tissues. A small number of clinical trials have provided evidence of cardiac benefit from morphine or remifentanil in cardiopulmonary bypass or coronary angioplasty patients, although further trials of subtype-specific opioid receptor agonists are needed. The precise roles and utility of this GPCR family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on opioid receptor signalling and protective responses.

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Section: The Opioid Receptor System Orchestrates Cellular To Organismmentioning

confidence: 97%

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Headrick

Hoe

Toit

et al. 2015

British J Pharmacology

134

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“…The cardioprotection conferred by TAN-67 was subsequently reversed with the use of the selective ␦ 1 antagonist 7-benzylidenenaltrexone (BNTX). Chien et al (5) also reported that ␦ 1 -agonists helped to preserve the viability of multiorgan preparations. Because the activation of cholinergic receptors has also been implicated in cardioprotection (34), a potential link between opioids and vagal function might be physiologically important.…”

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confidence: 99%

Cardiac enkephalins interrupt vagal bradycardia via δ₂-opioid receptors in sinoatrial node

Farias

Jackson

Yoshishige

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Local cardiac opioids appear to be important in determining the quality of vagal control of heart rate. Introduction of the endogenous opioid methionine-enkephalin-arginine-phenylalanine (MEAP) into the interstitium of the canine sinoatrial node by microdialysis attenuates vagally mediated bradycardia through a delta-opioid receptor mechanism. The following studies were conducted to test the hypothesis that a delta(2)-opiate receptor subtype mediates the interruption of vagal transmission. Twenty mongrel dogs were anesthetized and instrumented with microdialysis probes inserted into the sinoatrial node. Vagal frequency responses were performed at 1, 2, and 3 Hz during vehicle infusion and during treatment with the native agonist MEAP, the delta(1)-opioids 2-methyl-4aa-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydroquinolino[2,3,3- g]isoquinoline (TAN-67) and [d-pen(2,5)]-enkephalin (DPDPE), and the delta(2) opioid deltorphin II. The vagolytic effects of intranodal MEAP and deltorphin were then challenged with the delta(1)- and delta(2)-opioid receptor antagonists 7-benzylidenenaltrexone (BNTX) and naltriben, respectively. Although the positive control deltorphin II was clearly vagolytic in each experimental group, TAN-67 and DPDPE were vagolytically ineffective in the same animals. In contrast, TAN-67 improved vagal bradycardia by 30-35%. Naltriben completely reversed the vagolytic effects of MEAP and deltorphin. BNTX was ineffective in this regard but did reverse the vagal improvement observed with TAN-67. These data support the hypothesis that the vagolytic effect of the endogenous opioid MEAP was mediated by delta(2)-opioid receptors located in the sinoatrial node. These data also support the existence of vagotonic delta(1)-opioid receptors also in the sinoatrial node.

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“…S elective d receptor agonists have been shown to confer ischemic preconditioning (IPC) to myocardium, 1-6 brain, 7-9 multiorgan blocks, 10 and myocardial cell culture. 11 d receptor agonists specific for d 1 and d 2 receptor subtypes have also been shown to provide delayed (24-48 hours) or pharmacologic ischemic precon-ditioning (PPC) to ischemic myocardium.…”

mentioning

confidence: 99%

“…[12][13][14][15] The IPC and PPC are believed to operate through a mechanism(s) requiring activation of G i/o proteins, 15,16 translocation of protein kinase C d isoform 17 and subsequent activation of mitochondrial and sarcolemmal K ATP channel opening, 15,18,19 and lessening of myocardial oxygen requirements. [3][4][5][6][7][8][9][10] Polyubiquitin expression has also been implicated in the response to ischemic stress both in heart and brain. 20,21 We have recently demonstrated that IPC with the highly specific d 2 receptor agonist Deltorphin-D variant (Delt-D var ), but not the nonspecific d receptor agonist D-Ala 2 -Leu 5 -Enkephalin (DADLE), resulted in significantly reduced total polyubiquitin transcript expression in rat myocardium, thereby indicating d 2 opioid IPC modulation of the ubiquitin stress pathway.…”

mentioning

confidence: 99%

24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

Oeltgen

Govindaswami

Witzke

2006

Academic Emergency Medicine

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Objectives: d opioids have been shown to confer ischemic preconditioning and pharmacologic ischemic preconditioning to the myocardium. However, their role in providing extended pharmacologic ischemic preconditioning in hemorrhagic shock has not been explored. The authors examined the effects of 24-hour preinfusions of a selective d opioid receptor agonist, Deltorphin-D variant (Delt-D var ), on hemodynamic stability and duration of survival in a rat model of severe hemorrhagic shock.Methods: Conscious Sprague-Dawley rats with indwelling catheters were hemorrhaged at a rate of 3.18 mL/l00 g over 20 minutes. Twenty-four hours before hemorrhage, the control group (n = 14) was infused with 1.0 mL lactated Ringer's solution, and the Delt-D var -treated group (n = 22) was infused with 5.0 mg/kg Delt-D var in 1.0 mL lactated Ringer's solution. Rats were continuously monitored for heart rate (HR), mean arterial pressure, and four-hour survival rates. Plasma lactate levels were determined at the beginning of hemorrhage and the end of hemorrhage.Results: At 240 minutes, only one of 14 controls (7.1%) survived, while 16 (72.7%) of the 22 experimental rats survived. No significant differences in heart rate between controls and Delt-D var -treated rats were noted. Increases in mean arterial pressure of Delt-D var -treated rats at the beginning of hemorrhage and at the end of hemorrhage were found to be significant (p < 0.05). At 240 minutes, heart rate and mean arterial pressure were not different between the single surviving control and the Delt-D var group. At the end of hemorrhage, lactate levels in the Delt-D var -treated group were 8.5 (AE0.5) mmol/L versus 10.8 (AE0.6) mmol/L (p < 0.05) in the control group.Conclusions: Twenty-four-hour pretreatment with Delt-D var decreases plasma lactate levels and improves hemodynamic stability and survival during hemorrhagic shock. The use of d-specific opioids may improve survival from hemorrhagic shock and have clinical utility in providing ischemic protection in scenarios of planned ischemia.ACADEMIC EMERGENCY MEDICINE 2006; 13:127-133 ª

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Extension of tissue survival time in multiorgan block preparation with a delta opioid DADLE ([D-Ala2,D-Leu5]-enkephalin)

Abstract: , wei reported our results with a newly developed, autoperfused, multiorgan block preparation for long-term organ

Cited by 72 publications

References 6 publications

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Cardiac enkephalins interrupt vagal bradycardia via δ₂-opioid receptors in sinoatrial node

24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

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Extension of tissue survival time in multiorgan block preparation with a delta opioid DADLE ([D-Ala2,D-Leu5]-enkephalin)

Abstract: , wei reported our results with a newly developed, autoperfused, multiorgan block preparation for long-term organ

Cited by 72 publications

References 6 publications

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Cardiac enkephalins interrupt vagal bradycardia via δ2-opioid receptors in sinoatrial node

24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

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Cardiac enkephalins interrupt vagal bradycardia via δ₂-opioid receptors in sinoatrial node