Nitric oxide signaling in the ischemic postconditioning of human heart muscle (RCD code: III)
Background: Ischemic heart conditioning is well documented to trigger the intrinsic protective mechanisms of resistance against ischemia/reperfusion (I/R) injury. Previous studies on animal model have suggested that the nitric oxide (NO) mediates the beneficial effect of ischemic postconditioning (POC). We tested the hypothesis that POC provide cardioprotection in the NO-dependent mechanism in the human myocardium.
Methods: Human atrial trabeculae were subjected to simulated I/R injury. To achieve POC triple brief hypoxia periods were followed by the lethal hypoxia. Non-selective inhibitor of NO synthase: NG-monomethyl-L-arginine (L-NMMA) was used at the time of re-oxygenation in the POC protocol. 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 cardiac muscle relaxation – as the rate of decay of the force of a contraction (Slope T).
Results: Co-application of L-NMMA with POC resulted in the decrease of Amax, Slope L and Slope T during re-oxygenation period as compared to POC only.
Conclusions: At re-oxygenation period, the blockade of NO synthesis has deleterious effect on systolic and diastolic function of human myocardium, as well as attenuates the beneficial effect of ischemic.
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