Myocardial
ischemic postconditioning (PosC) describes an acquired resistance to lethal
ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R applied immediately after the ischemic insult. Cardioprotection is conveyed by parallel signaling pathways converging to prevent mitochondria permeability transition. Recent observations indicated that PostC is associated with
free radicals generation, including
nitric oxide (NO(.)) and
superoxide (O2 (.-)), and that cardioprotection is abrogated by
antioxidants. Since NO. And O2 (. -) react to form
peroxynitrite, we hypothesized that postC might trigger the formation of peroxyntrite to promote cardioprotection in vivo. Rats were exposed to 45 min of
myocardial ischemia followed by 3h reperfusion. PostC (3 cycles of 30 seconds
ischemia/30 seconds reperfusion) was applied at the end of index
ischemia. In a subgroup of rats, the
peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato
iron (FeTPPS) was given intravenously (10 mg/kg(-1)) 5 minutes before PostC. Myocardial
nitrotyrosine was determined as an index of
peroxynitrite formation.
Infarct size (colorimetric technique and plasma
creatine kinase-CK-levels) and left ventricle (LV) function (micro-tip
pressure transducer), were determined. A significant generation of
3-nitrotyrosine was detected just after the PostC manoeuvre. PostC resulted in a marked reduction of
infarct size, CK release and
LV systolic dysfunction. Treatment with FeTPPS before PostC abrogated the beneficial effects of PostC on
myocardial infarct size and LV function. Thus,
peroxynitrite formed in the myocardium during PostC induces cardioprotective mechanisms improving both structural and functional integrity of the left ventricle exposed to
ischemia and reperfusion in vivo.