Females Exhibit Relative Resistance to Depressive Effects of Tumor Necrosis Factor-α on the Myocardium

Background Tumor necrosis factor-alpha (TNF-α) 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...

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Published in:The Journal of surgical research 2008-11, Vol.150 (1), p.92-99
Main Authors: Sando, Ian C., B.E, Wang, Yue, Ph.D, Crisostomo, Paul R., M.D, Markel, Troy A., M.D, Sharma, Rahul, B.S, Erwin, Graham S, Guzman, Mike J., B.A, Meldrum, Daniel R., M.D, Wang, Meijing, M.D
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Animals
Biological and medical sciences
Depression
estrogen
Estrous Cycle
Female
gender differences
General aspects
In Vitro Techniques
Male
Medical sciences
Mood disorders
Myocardial Contraction - drug effects
myocardial function
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Rats
Rats, Sprague-Dawley
Sex Characteristics
Surgery
testosterone
TNF
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Background Tumor necrosis factor-alpha (TNF-α) 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. Materials and 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. Conclusion 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.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2007.12.777