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 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.