Abstract:
BACKGROUND:Gender differences have been noted in acute ischemia/reperfusion injury. Estrogen and the estrogen receptors (ER) appear to play a critical role in cardiovascular gender differences, given that females have improved myocardial functional recovery associated with decreased tissue inflammation. It has been suggested that ER beta plays a part in decreasing myocardial inflammation following hemorrhage. It remains unknown, however, whether ER beta also may be protective following the more severe insult of complete global, normothermic ischemia/reperfusion injury in the isolated mouse heart. METHODS:Adult male and female wild-type (WT) and ER beta knockout (ERbKO) mouse hearts were subjected to 20 minutes ischemia and 60 minutes reperfusion (Langendorff model). Myocardial contractile function (+/-dP/dt) was continuously recorded. Heart tissue was analyzed for tumor necrosis factor, interleukin (IL)-1 beta, IL-6, and IL-10 levels as determined by enzyme-linked immunosorbent assay. RESULTS:Females had markedly improved functional recovery compared with males following ischemia/reperfusion. This recovery was associated with lower levels of myocardial tumor necrosis factor, IL-1 beta, and IL-6 in females. However, ERbKO females exhibited significantly less postischemic functional recovery than WT females and were similar to WT males. Interestingly, increased myocardial production of tumor necrosis factor, IL-1 beta, and IL-6 was noted in ERbKO female hearts in response to ischemia/reperfusion. No significant differences were found between male WT and male ERbKO in postischemic functional recovery and proinflammatory cytokine production. CONCLUSION:ER beta plays a role in the protective effects of estrogen following global, warm ischemia/reperfusion of the isolated mouse heart. This understanding ultimately may enable the development of pharmaceutical agents that harness such protection with minimal collateral sex hormone effects.
journal_name
Surgeryjournal_title
Surgeryauthors
Wang M,Crisostomo PR,Markel T,Wang Y,Lillemoe KD,Meldrum DRdoi
10.1016/j.surg.2008.03.009subject
Has Abstractpub_date
2008-08-01 00:00:00pages
233-8issue
2eissn
0039-6060issn
1532-7361pii
S0039-6060(08)00172-4journal_volume
144pub_type
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