While restoration of Mood flow is ihe sole method of salvaging ischémie my ocardial tissue, reperfusiori can result in additional damage, the severity of which increases with ago. Keperfusion and aging are associated with increased rates of mitorhomlrial free radical production and subsequent j>eroxid;ilion <>! membrane Hpids. Known to increase in concentration upon reperfu.sion of car diar tissue, -l-liydroxv-2- nonenal ( UN K), a major product of lipid peroxidation, can react with and inactivate en/ymes. We hypothesize that: Reperfusion induced declines in mitochondria! respiration are due, in part, to modification of specific mitochondrial proteinf sy by U N K and t liât these processes con t ri bu te to age-related increases in mvocardial reperfusion injury. Hearts isolated from S- and 24-month old rals were perfused in I.angendorff fashion and subjected to varying periods of ischemia and/or reperfusion. Mitochondria isolated from hearts exposed to ischemia (25 ruin ) exhibited slight declines in State 3 respira t ion, the degree of whit h was not dependent on age. Upon reperfusion ( 10 min j. mitochondria, from senescent hearts exhibited a greater reperfusion-related de cline in state -I respiration when compared to adult rat hearts. Reperfusion resulted in the modification of two mitochondria! proteins ( 30 and -45 kua,i by HNF. The level of modification increased with age. The identity of these proteinfsj is under investigation. 1 he results establish, for 1 he first time, free radical mechanisms of re per fusion i n jury lo cardiac mitochondria and t fir ton tribut ion nf these ]"n",rsse> 10 ohscm-d ..<y rciat.-d iri<rc:i.s<-s in damage.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology