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.
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.
Authors: Nicholas D Vornehm; Meijing Wang; Aaron Abarbanell; Jeremy Herrmann; Brent Weil; Jiangjing Tan; Yue Wang; Megan Kelly; Daniel R Meldrum Journal: Surgery Date: 2009-08 Impact factor: 3.982