Low concentrations of an nitric oxide-donor combined with a liposoluble antioxidant compound enhance protection against reperfusion injury in isolated rat hearts

Nitric oxide (no) and reactive oxygen species (ros) are double-edged swords in reperfused hearts. the effects of a no-donor and an antioxidant compound against ischemia/reperfusion were studied. the compounds were tested separately,as a mixture and as a new hybrid molecule containing both leads. isolated rat hearts underwent 30 min global ischemia and 2 hrs reperfusion. compounds were infused either at 1 or 10 μm concentrations during the first 20 min of reperfusion. hybrid was also tested in the presence of mitochondrial k+ atp-sensitive (mkatp) channel blockade by 5-hd (100 μm). reduction of infarct size and recovery of left ventricular developed pressure during reperfusion were evaluated. when given at 1 μm concentration,hybrid significantly improved all indices of protection; its beneficial effects were abolished by mkatp channel blockade. at the same concentration,mixture and no-donor alone improved recovery of left ventricular developed pressure but did not reduce infarct size; antioxidant was ineffective. when given at 10 μm concentration,antioxidant and mixture improved all parameters of protection; no-donor and hybrid were ineffective. our data suggest that different signaling cascades could be elicited by low and high concentrations of antioxidant compound and/or no-donor. it is likely that a different no-induced release of reactive oxygen species via mkatp channel activation may play a pivotal role in affecting infarct size and post-ischemic contractile recovery.