New perspectives on the cardioprotective phosphonate effect of the spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: An hemodynamic and P-31 NMR study in rat hearts

The spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) is an improved ESR probe to assess superoxide (O-2(.-)) formation in the po stischemic heart. We recently found that DEPMPO pretreatment improves recov ery of cardiac function with the concomitant inhibition of postischemic O-2 (.-) production. By perfusing diethyl methylphosphonate MeP(O)(OEt)(2) to i schemic-reperfused isolated rat hearts, we provide hemodynamic evidence tha t this preservation, which exerts during ischemia, is in fact specific to t he phosphonate group. Using P-31 NMR on intact rat hearts, it was also foun d that the "phosphonate effect" of DEPMPO is related to the preservation of ATP levels during ischemia, when compared to 5,5-dimethyl-1-pyrroline N-ox ide. This mechanism may be a means of reducing the potency of cardiac tissu e to produce O-2(.-) during reperfusion. (C) 1999 Elsevier Science Inc.