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Background: Opioidergic conditioning is well documented to trigger cardioprotection against ischemia/ reperfusion (I/R) injury. Previous studies on animal models have suggested that nitric oxide (NO) mediates the beneficial effect of opioids, but the role of NO in humans seems to be controversial., Objectives: The aim of the study was to assess the influence of NO modulators on opioid-induced cardioprotection in the human myocardium., Material and Methods: Trabeculae of the human right atria were electrically driven in an organ bath and subjected to simulated I/R injury. The non-selective inhibitor of nitric oxide synthase (NOS) - N-methyl-l-arginine (LNMMA), the donor of NO - S-Nitroso-N-acetylpenicillamine (SNAP) or morphine (in the amount of 10-4 M) were used at the time of re-oxygenation. The additional trabecula was subjected to the hypoxia protocol only (control). The contractility 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 the cardiac muscle relaxation - as the rate of decay of the force of a contraction (Slope T)., Results: The application of 100 μM LNMMA resulted in the decrease of Amax, Slope L and Slope T during the re-oxygenation period as compared to control. The application of 10-4 M morphine and/or 100 μM SNAP resulted in a partial reversal of the detrimental influence of LNMMA., Conclusions: At the re-oxygenation period, the blockade of NO synthesis has a deleterious effect on the systolic and diastolic function of the human myocardium as well as attenuates the beneficial effect of morphine conditioning.

Background: Despite progress in the invasive treatment of ischemic heart disease, the ability to limit ischemia-reperfusion (I/R) injury remains largely unrealized. Ischemic pre-conditioning (IPC) and post-conditioning (POC) induce the protective mechanisms of resistance against I/R injury. Stimulation of opioid receptors mimic the protective effect of IPC or POC in an animal models. We tested the hypothesis, that IPC and POC provide cardioprotection in opioid-dependent mechanism in human myocardium., Methods: Human atrial trabeculae were subjected to I/R injury. To achieve IPC, single hypoxia period preceded the applied lethal hypoxia, to achieve POC triple hypoxia periods followed lethal hypoxia. Naloxone was used at the onset of lethal hypoxia in IPC protocol, and at the time of re-oxygenation in POC protocol. Contractive function of the myocardium was assessed as maximal force of contraction (Amax), rate of rise of force of contraction (+dV/dT) and diastolic parameter - rate of decay of force of contraction (-dV/dT)., Results: Co-application of naloxone with IPC or POC resulted in decrease of Amax, +dV/dT and -dV/dT during re-oxygenation period as compared to IPC or POC only., Conclusions: Naloxone abrogates beneficial effect of IPC and POC. IPC and POC in humans provide cardioprotection in opioid receptor system dependent mechanism.

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 hu-man 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 myo-cardium 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).