New perspectives on the cardioprotective phosphonate effect of the spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: an hemodynamic and 31P 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 (O2•−) formation in the postischemic heart. We recently found that DEPMPO pretreatment improves recovery of cardiac function with the concomitant inhibition of postischemic O2•− production. By perfusing diethyl methylphosphonate MeP(O)(OEt)2 to ischemic-reperfused isolated rat hearts, we provide hemodynamic evidence that this preservation, which exerts during ischemia, is in fact specific to the phosphonate group. Using 31P NMR on intact rat hearts, it was also found 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-oxide. This mechanism may be a means of reducing the potency of cardiac tissue to produce O2•− during reperfusion.