Opioidergic conditioning of the human heart muscle in nitric oxide-dependent mechanism.

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 cardio-protection in the human myocardium. Material and methods. Trabeculae ofthe 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 tra becu la 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 mu M 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 mu M 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.