title: Females exhibit relative resistance to depressive effects of tumor necrosis factor-alpha on the myocardium.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in myocardial dysfunction following acute injury. It is unknown, however, if a gender-specific response to TNF infusion exists in isolated rat hearts. Elucidating such mechanisms is important to understanding the myocardial gender differences during acute injury. We hypothesize that females will exhibit a relative resistance to TNF-induced myocardial dysfunction compared to males and that menstrual cycle would influence the degree of female myocardial resistance to TNF-induced myocardial functional depression.
  
  
  METHODS
  Adult male, proestrus female, and metestrus/diestrus female hearts were subjected to 60 min of TNF infusion at 10,000 pg/mL.min via Langendorff. Myocardial contractile function (left ventricular developed pressure, and the positive/negative first derivative of pressure) was continuously recorded.
  
  
  RESULTS
  10,000 pg/mL.min of TNF markedly depressed myocardial function in males compared with other doses of TNF. Myocardial function was significantly decreased in males compared to females following TNF infusion. Additionally, both the proestrus and the metestrus/diestrus females exhibited equal resistance to TNF-induced myocardial dysfunction.
  
  
  CONCLUSIONS
  Our study shows that females exhibit a significantly greater degree of resistance to TNF-induced myocardial depression. Moreover, data from this study suggest that fluctuations in estrogen during the reproductive cycle may have little to no influence on TNF-induced myocardial depression.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Sando
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crisostomo
authors.forename: Troy A
authors.initials: TA
authors.lastname: Markel
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Graham S
authors.initials: GS
authors.lastname: Erwin
authors.forename: Mike J
authors.initials: MJ
authors.lastname: Guzman
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: Meijing
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D030762:Estrous Cycle; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha