Age-Related Gender Differential in Outcome After Blunt or Penetrating Trauma

George, Richard L.; McGwin, Gerald; Windham, Samuel T.; Melton, Sherry M.; Metzger, Jesse; Chaudry, Irshad H.; Rue, Loring W.

doi:10.1097/00024382-200301000-00006

Cited by 140 publications

(101 citation statements)

References 25 publications

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“…In a recent study of 5192 patients at a level I trauma center (59), Deitch et al found that hormonally active women have a better physiologic response to similar degrees of shock and trauma than do their male counterparts. Though several clinical studies demonstrated the influence of sex in the outcome following trauma, several studies were unable to identify any such association (3,(60)(61)(62). One of the reasons for contradictory or less convincing evidence for the influence of sex postinjury, and in sepsis in some studies in the human, may be heterogeneity of the population studied in relation to their hormonal status.…”

Section: Sex Dichotomy In Trauma Outcomementioning

confidence: 99%

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Raju

Bland

Chaudry

2008

Mol Med

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ESTROGEN, MECHANISM OF ACTIONE2, the female hormone, is mainly produced by the ovaries and the placenta. The three major estrogens in women are estradiol, estriol, and estrone ( Figure 1). Estrogens are synthesized from androgens by the loss of C-19 angular methyl group and the formation of an aromatic A ring. Whereas estradiol is derived from testosterone, estrone is derived from androstenedione. The main form of E2 in women Trauma-hemorrhage leads to prolonged immune suppression, sepsis, and multiple organ failure. The condition affects all compartments of the immune system, and extensive studies have been carried out elucidating the immunological events following trauma-hemorrhage. The immune alteration observed following trauma-hemorrhage is gender dependent in both animal models and humans, though some studies in humans are contradictory. Within 30 min after trauma-hemorrhage, splenic and peritoneal macrophages, as well as T-cell function, are depressed in male animals, but not in proestrus females. Studies have also shown that the survival rate and the induction of subsequent sepsis following trauma-hemorrhage are significantly higher in males and ovariectomized females compared with proestrus females. These and other investigations show that sex hormones form the basis of this gender dichotomy, and administration of estrogen can ameliorate the immune depression and increase the survival rate after trauma-hemorrhage. This review specifically elaborates the studies carried out thus far demonstrating immunological alteration after trauma-hemorrhage and its modulation by estrogen. Also, estrogen was shown to produce its salutary effects through nuclear as well as extranuclear receptors. Estrogen rapidly activates several protein kinases and phosphatases, as well as the release of calcium in different cell types. The results of the studies exemplify the promise of estrogen as a therapeutic adjunct in treating adverse pathophysiological conditions following trauma-hemorrhage.

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Section: Sex Dichotomy In Trauma Outcomementioning

confidence: 99%

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Raju

Bland

Chaudry

2008

Mol Med

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“…All analyses were carried out in the same population of T lymphocytes prepared from one mouse in each group or from a pooled population of lymphocytes prepared from two mice in each group. Approximately 10 9 lymphocytes were used for preparation of homogenate in enzyme assays, 10 6 lymphocytes for mRNA expression by PCR analysis, and 5 ϫ 10 6 for bioassays. Enzyme assays.…”

Section: Chemicalsmentioning

confidence: 99%

Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17β-estradiol

Samy

Zheng

Matsutani

et al. 2003

American Journal of Physiology-Cell Physiology

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and resuscitation (TH) produces profound immunodepression and enhances susceptibility to sepsis in males but not in proestrus females, suggesting gender dimorphism in the immune responses. However, the mechanism responsible for the maintenance of immune functions in proestrus females after TH is unclear. Splenic T lymphocytes express receptors for estrogen (ER), contain enzymes involved in estrogen metabolism, and are the major source of cytokine production; the metabolism of 17␤-estradiol was assessed in the splenic T lymphocytes of proestrus and ovariectomized mice by using appropriate substrates after TH. Analysis for aromatase and 17␤-hydroxysteroid dehydrogenases indicated increased 17␤-estradiol synthesis and low conversion into estrone in T lymphocytes of proestrus but not of ovariectomized mice. The effect of 17␤-estradiol on T lymphocyte cytokine release was reliant on ER expressions. This was apparent in the differences of ER expression, especially that of ER-␤, and an association between increased 17␤-estradiol synthesis and sustained release of IL-2 and IL-6 in T lymphocytes of proestrus females after TH. Because 17␤-estradiol is able to regulate cytokine genes, and the splenic T lymphocyte cytokine releases is altered after TH, continued synthesis of 17␤-estradiol in proestrus females appears to be responsible for the maintenance of T lymphocyte cytokine release associated with the protection of immune functions after TH. inflammation; immune suppression; steroid synthesis; T lymphocytes; cytokines THE INFLUENCE OF GENDER on immune functions has been recognized for many years, and in general, women are known to develop enhanced humoral responses compared with men and are more prone to autoimmune diseases (9,12,20). Trauma-hemorrhage and resuscitation (TH) produce severe impairment of both immune and cardiovascular functions (51,56,57). Although depression of cellular immunity occurs very early following TH, the loss in immune functions persists for a prolonged period, which may lead to subsequent sepsis with high mortality rates (43, 56). The immune depression is pronounced in males and ovariectomized females (OVX) after TH compared with proestrus females (54, 55). Moreover, immune functions in males and OVX females can be restored by the administration of 17␤-estradiol (E2) after TH (16-18). Thus gender dimorphism is obvious in the loss of immune functions after TH, implicating a major role for sex steroid hormones (2, 4).Steroid hormones regulate immune functions in vivo, and the mechanisms involve not only the control of cytokine gene transcription by the classic steroid hormone-receptor complex but also the tissue-specific metabolism of sex steroids (11,21,24,29,33,36,47). Among the sex steroids, estrogen is demonstrated to protect immune functions after TH because proestrus females are not immunodepressed compared with male and OVX mice. Furthermore, the depressed immune functions in males and OVX females after TH can be normalized by parenteral E2 administration (16-18). The ovary is the prima...

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“…Women are more susceptible to hypovolemic circulatory stress than men (6,13,17,18,48), and clinical studies have found decreased survival in women after penetrating injury as well as burn injuries (19,35). The mechanisms underlying the susceptibility are not entirely clear and are probably multifactorial (17).…”

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confidence: 99%

Lower capacitance response and capillary fluid absorption in women to defend central blood volume in response to acute hypovolemic circulatory stress

Lindenberger¹,

Olsen²,

Länne³

2008

American Journal of Physiology-Heart and Circulatory Physiology

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Lindenberger M, Olsen H, Lä nne T. Lower capacitance response and capillary fluid absorption in women to defend central blood volume in response to acute hypovolemic circulatory stress. Am J Physiol Heart Circ Physiol 295: H867-H873, 2008; doi:10.1152/ajpheart.00332.2008.-Acute hemorrhage is a leading cause of death in trauma, and women are more susceptible to hypovolemic circulatory stress than men. The mechanisms underlying the susceptibility are not clear, however. The aim of the present study was to examine the compensatory mechanisms to defend central blood volume during experimental hypovolemia in women and men. Twentytwo women (23.1 Ϯ 0.4 yr) and 16 men (23.2 Ϯ 0.5 yr) were included. A lower body negative pressure (LBNP) of 11-44 mmHg induced experimental hypovolemic circulatory stress. The volumetric technique was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as to assess net capillary fluid transfer from tissue to blood in the arm. Plasma norepinephrine (NE) and forearm blood flow were measured before and during hypovolemia, and forearm vascular resistance (FVR) was calculated. LBNP created comparable hypovolemia in women and men. FVR increased less in women during hypovolemic stress, and no association between plasma NE and FVR was seen in women (R 2 ϭ 0.01, not significant), in contrast to men (R 2 ϭ 0.59, P Ͻ 0.05). Women demonstrated a good initial capacitance response, but this was not maintained with time, in contrast to men [e.g., decreased by 24 Ϯ 4% (women) vs. 4 Ϯ 5% (men), LBNP of 44 mmHg, P Ͻ 0.01], and net capillary fluid absorption from tissue to blood was lower in women (0.086 Ϯ 0.007 vs. 0.115 Ϯ 0.011 ml ⅐ 100 ml Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.05). In conclusion, women showed impaired vasoconstriction, reduced capacitance response with time, and reduced capillary fluid absorption during acute hypovolemic circulatory stress, indicating less efficiency to defend central blood volume than men.gender; orthostatic tolerance; baroreceptor sensitivity ACUTE HEMORRHAGE is a leading cause of death in trauma (2, 41). Women are more susceptible to hypovolemic circulatory stress than men (6,13,17,18,48), and clinical studies have found decreased survival in women after penetrating injury as well as burn injuries (19,35). The mechanisms underlying the susceptibility are not entirely clear and are probably multifactorial (17).Lower body negative pressure (LBNP) is an excellent model for acute hemorrhage and hypovolemic circulatory stress, by inducing central hypovolemia and unloading of baroreceptors (8). A decreased baroreceptor sensitivity has been proposed in women by several authors (13,27,42), and women seem to respond with diminished arterial vasoconstriction to the infusion of ␣-receptor agonists (4, 14, 26). Furthermore, a more pronounced decrease in stroke volume and cardiac output has been postulated as the main mechanism for the susceptibility to hypovolemic circulatory stress, due to smaller and functionally stiffer hearts and ...

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Age-Related Gender Differential in Outcome After Blunt or Penetrating Trauma

Cited by 140 publications

References 25 publications

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17β-estradiol

Lower capacitance response and capillary fluid absorption in women to defend central blood volume in response to acute hypovolemic circulatory stress

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