Aim: 

Production of reactive oxygen species (ROS) and lack of nitric oxide (NO) release characterize reperfusion after myocardial ischemia. The investigation aimed to see whether a compound with antioxidant and NO donor properties reduces infarct size if given at the beginning of reperfusion.

Method: 

We evaluated the effects of a newly synthesized NO-donor and antioxidant hybrid compound (HYB), obtained by joining the NO-donor (NOD) furoxan-3-carboxamide with the antioxidant (AOX) phenol substructure, in comparison with that of each of the leads given separately. Isolated rat hearts, perfused at constant flow with oxygenate buffer, underwent 30 min of global ischemia and 2 hrs of reperfusion. Drugs were added to the perfusion buffer at 1 or 10 mM concentrations during the first 20 min of reperfusion. Protection was assessed from the reduction of infarct size and the recovery of left ventricular developed pressure (LVDP).

Results: 

The indices of protection were improved when HYB was administered at the concentration 1 mM, but not at the concentration of 10 mM. At 1 mM concentration, NOD improved recovery of LVDP, but it did not reduce infarct size. On the contrary, AOX was effective in reducing the infarct size only if given at the concentration of 10 mM.

Conclusion: 

The protection by the 1 mM HYB can be attributed to the cascade elicited by NO, in which a role is played by ROS: when their release is moderate in response to a small concentration of NO, they can induce protection, while, if released in large amount in response of a large production of NO, their deleterious effect prevails. 1 mM HYB induces myocardial protection because of its moderate release of NO and its scavenger activity of ROS.