PBN spin trapping of free radicals in the reperfusion-injured heart. Limitations for pharmacological investigations

摘要: Post-ischemic reperfusion causes cardiac dysfunction and radical-induced lipid peroxidation (LPO) detectable by ESR spin trapping. This study deals with the applicability of trapping technique to pharmacological investigations during myocardial injury. The use trap phenylbutylnitrone (PBN, 3 mM) in isolated rat hearts demonstrated release alkoxyl radicals (aN= 1.39 mT, aH s= 0.19 mT) formed particularly within first 15 min following 30 ischemia. decline radicals, after 10 reperfusion, was accompanied recovery function 80% hearts. radical concentration coronary effluent (maximum 7.5 min) reduced infusion 1 mM mercaptopropionylglycine (MPG, 2.7 ± 0.5 U/ml, p < 0.001) or μM vitamin E (11.7 0.8 0.001), compared (PBN-containing) control (29.7 4.3 U/ml). Moreover, functional (left ventricular developed pressure, LVDP 91.6 20% pre-ischemic level, 0.05) improved hydrophilic scavenger MPG, (LVDP 50.5 15.7% baseline). PBN alone led higher (p VF (duration fibrillation; 7.10 0.36 min/30 min, 0.05), untreated (PBN-free) 26.6 11.8%; 19.42 3.64 min). Ca antagonist verapamil (0.1 μM), lipophilic showed cardioprotection absence PBN: post-ischemic 25.4 6.8% 39.6 12.7% 52.4 2.6% 0.01), respectively, corresponding (13.3 6.6%). Whereas were able protect heart when present alone, they offered no additive effect presence PBN. Therefore, can be used estimate properties an agent heart. However, because protective itself, results simultaneous effects other compounds, such as antagonists scavengers, on may limited. (Mol Cell Biochem 186: 107-115, 1998)