‘Opioidergic postconditioning’ of heart muscle during ischemia/reperfusion injury
Abstract
Background: Ischemic preconditioning and postconditioning are the novel strategies of attaining cardioprotection against ischemia/reperfusion (I/R) injury. Previous studies suggested the role of opioid pathway, however the class of opioid receptors responsible for this effect in humans remains unknown. The aim of the study was to assess the influence of opioids on simulated I/R injury outcomes in the human myocardium.
Methods: Trabeculae of the human right atrium were electrically driven in organ bath and subjected to simulated I/R injury. Morphine (10–4M, 10–5M, 10–6M) or d-opioid receptor agonist DADLE (10–8M, 10–7M, 10–6M) was used at the time of re-oxygenation. Additional trabecula was subjected to hypoxia protocol only (Control). Contractive force of the myocardium was assessed as the maximal force of a contraction (Amax), the rate of rise of the force of a contraction (Slope L) and relaxation as the rate of decay of the force of a contraction (Slope T).
Results: Application of morphine 10–4M resulted in increase of Amax, Slope L and Slope T during re-oxygenation period as compared to Control (77.99 ± 1.5% vs. 68.8 ± 2.2%, p < 0.05; 45.72 ± 2.9% vs. 34.12 ± 5.1%, p < 0.05; 40.95 ± 2.5% vs. 32.37 ± 4.3%, p < 0.05). Parameters were not significantly different in the lower morphine concentrations. Application of DADLE 10–6M resulted in decrease of Amax and Slope L as compared to Control (68.13 ± 5.5% vs. 76.62 ± 6.6%, p < 0.05; 28.29 ± 2.2 vs. 34.80 ± 3.9%, p < 0.05).
Conclusions: At re-oxygenation, morphine improves systolic and diastolic function of the human myocardium in the dose-dependent manner. Delta-opioid receptor stimulation attenuates systolic function of human heart muscle which remains in contrast to previous reports with animal models of I/R injury. (Cardiol J 2017; 24, 4: 419–425)
Keywords: ischemia reperfusion injurypostconditioningopioids
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