Go 6983 exerts cardioprotective effects in myocardial ischemia/reperfusion

Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction. Inhibiting protein kinase C (PKC inhibits the release of superoxide from PMNs. The compound Go 6983 is an inhibitor of all five PKC isoforms present in PMNs. Therefore, we hypothesized that Go 6983 could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs. We studied isolated rat hearts following ischemia (20 minutes) and reperfusion (45 minutes) infused with activated PMNs. In hearts reperfused with PMNs and Go 6983 (100 nM, n = 7), left ventricular developed pressure (LVDP) and the rate of LVDP (+dP/dt(max)) recovered to 89 +/- 7% and 74 +/- 2% of baseline values, respectively, at 45 minutes postreperfusion compared with I/R hearts (n = 9) receiving PMNs alone, which only recovered to 55 +/- 3% and 45 +/- 5% of baseline values for LVDP and +dP/d(max), respectively (P < 0.01). Go 6983 (100 nM) significantly reduced PMN adherence to the endothelium and infiltration into the myocardium compared with I/R+ PMN hearts (P < 0.01), and significantly inhibited superoxide release from PMNs by 90 +/- 2% (P < 0.01). In the presence of PMNs, Go 6983 attenuated post-I/R cardiac contractile dysfunction, which may be related in part to decreased superoxide production.