Aim of study: Previous reports note an increase in both reactive oxygen species (ROS) and nitric oxide (*NO) at the onset of myocardial reperfusion. We tested the hypothesis that inhibition of *NO or ROS production at the time of reperfusion improves recovery of post-ischemic myocardial function.
Methods and materials: Isolated rat hearts were perfused with temperature controlled (37.4 degrees C) modified Krebs Henseleit buffer solution at 85 mm Hg. Following 20 min of global ischemia, hearts were reperfused for the first 10 min with: (1) standard buffer (control), (2) buffer with a NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), (3) buffer with superoxide dismutase (SOD) or (4) buffer with N-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite generator. Tissue O(2) and *NO were continuously measured with thin electrochemical probes embedded in the wall of the LV. ROS was measured with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) (40 mM). LV contractile function was continuously monitored.
Results: Recovery of LV contractile function was significantly improved in hearts initially reperfused with L-NAME and SOD and significantly depressed in hearts reperfused with SIN-1 compared with control (p<0.01, n=5-8 per group). DMPO-adduct during reperfusion (measure of ROS) was significantly decreased with SOD (p<0.001 versus L-NAME and Control, n=4 per group) and unchanged with L-NAME and SIN-1 compared with Control. With L-NAME, tissue *NO and PO(2) were significantly decreased, independent of coronary flow, during reperfusion compared with control and SIN-1.
Conclusions: Inhibition of O(2)*(-) or *NO at the time of reperfusion improves early reperfusion LV function and alters tissue oxygen tension. In contrast to pre-ischemic treatments, intervention to reduce peroxynitrite generation at the onset of reperfusion can effectively improve post-ischemic myocardial recovery.