??-Opioid Receptor Antagonism Improves Recovery from Myocardial Stunning in Chronically Instrumented Dogs

Hartlage, Maike A. Grosse; Theisen, M.; Oliveira, Nelson P. Monteiro de; Aken, Hugo Van; Fobker, Manfred; Weber, Thomas P.

doi:10.1213/01.ane.0000237246.40665.34

Cited by 6 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most frequent causes of death from myocardial infarction are cardiogenic shock (52%), arrhythmias (25%), thromboembolism of the pulmonary artery (10%), and rupture of the left ventricle (5%) . These findings indicate that an antiarrhythmic drug could dramatically reduce mortality in this population.…”

Section: Antiarrhythmic Effect Of the Opioid Receptor Ligandsmentioning

confidence: 99%

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

Maslov

Khaliulin

Oeltgen

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

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.

show abstract

Section: Antiarrhythmic Effect Of the Opioid Receptor Ligandsmentioning

confidence: 99%

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

Maslov

Khaliulin

Oeltgen

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Evidence indicates that myocardial opioid-mediated receptor activation inhibits cardiac excitation-contraction coupling and protects the heart against hypoxia and ischemic injury, independent of enkephalin release [128]. Nor-BNI pretreatment increases dynorphin levels following myocardial stunning (transient ischemia; [129]). The detrimental effects and beneficial role of opioid-mediated KOP activation may be attributable to the concentration of endogenous dynorphin, stimulating exogenous opioids, or functional diversity in the response of inflammatory cells.…”

Section: Dynorphin-mediated Effects To Inflammation-induced Cardiac Injury-mentioning

confidence: 99%

Dynorphins in Development and Disease: Implications for Cardiovascular Disease

Cissom

Paris

Shariat‐Madar

2020

CMM

View full text Add to dashboard Cite

It is well-established that cardiovascular disease continues to represent a growing health problem and significant effort has been made to elucidate the underlying mechanisms. In this review, we report on past and recent high impact publications in the field of intracrine network signaling, focusing specifically on opioids and their interrelation with key modulators of the cardiovascular system and the onset of related disease. We present an overview of studies outlining the scope of cardiovascular and cerebrovascular processes that are affected by opioids, including heart function, ischemia, reperfusion, and blood flow. Specific emphasis is placed on the importance of dynorphin molecules in cerebrovascular and cardiovascular regulation. Evidence suggests that excessive or insufficient dynorphin could make an important contribution to cardiovascular physiology, yet numerous paradoxical observations frequently impede a clear understanding of the role of dynorphin. Thus, we argue that dynorphin-mediated signaling events for which an immediate regulatory effect is disputed should not be dismissed as unimportant, as they may play a role in cross-talk with other signaling networks. Finally, we consider the most recent evidence on the role of dynorphin during cardiovascular-related inflammation and on the potential value of endogenous and exogenous inhibitors of kappa-opioid receptor, a major dynorphin A receptor, to limit or prevent cardiovascular disease and its related sequelae.

show abstract

“…In another study, lipopolysaccharide activation of JNK caused disruption of fatty acid oxidation by a human ventricular-derived cardiomyocyte cell line and caused cardiac dysfunction in C57BL/6 mice ( Drosatos et al , 2011 ). However, in dogs ( Hartlage et al , 2006 ) and swine ( Coles et al , 2003 ), KORAn are cardioprotective. Also, negative inotropic ( Ventura et al , 1992 ) and pro-arrhythmic ( Bian et al , 1998 ) effects of U-50,488H and cardioprotective effects of nor-BNI ( Liu et al , 2005 ) are described in rats.…”

Section: Introductionmentioning

confidence: 99%

A Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of JDTic

Buda

Carroll

Kosten

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Animal studies suggest that kappa opioid receptor antagonists (KORAn) potentially could treat a wide variety of addictive and depressive disorders. We assessed the KORAn JDTic for safety, tolerability, and pharmacokinetics in a double-blind, placebo-controlled, randomized trial evaluating single oral doses in healthy adult males. Predose and postdose safety assessments included orthostatic vital signs; 6-lead continuous telemetry monitoring (approximately 16 h predose to 24 h postdose); 12-lead electrocardiograms (ECGs); clinical chemistry, hematology, coagulation, and urinalysis; psychomotor functioning (using the Wayne Saccadic Fixator (WSF)); and adverse events. As a potential indicator of JDTic effects on affect, the POMS Standard instrument was administered predose and daily postdose Days 1–6. At 1 mg, 2 of the 6 JDTic (and 0/6 placebo) subjects experienced a single, asymptomatic event of multiple beats of nonsustained ventricular tachycardia (NSVT). Their events were temporally similar with respect to time postdose (and the postdose timing of an NSVT event in a monkey). These events triggered a study stopping rule. No differences were observed between the placebo and JDTic subjects with respect to clinical chemistry, hematology, coagulation, urinalysis, orthostatic vital signs, WSF, or 12-lead ECG parameters. Plasma JDTic levels were below the lower limit of quantitation (0.1 nM) in all subjects. There were no significant differences in POMS scores between the placebo and JDTic groups. Although the evidence is circumstantial, it suggests that NSVT is a potential JDTic toxicity in humans. Given the therapeutic potential of KORAn, further investigation is needed to determine whether a significant JDTic human cardiac effect indeed exists, and if so, whether it is specific to JDTic or represents a KORAn class effect.

show abstract

??-Opioid Receptor Antagonism Improves Recovery from Myocardial Stunning in Chronically Instrumented Dogs

Cited by 6 publications

References 36 publications

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

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

Dynorphins in Development and Disease: Implications for Cardiovascular Disease

A Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of JDTic

Contact Info

Product

Resources

About