This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (11)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Emergency Medicine  • Surgical Physiology, Other  • Men's Health, Other  • Women's Health  • Women's Health, Other  • Hepatobiliary Surgery  • Alert me on articles by topic

Balazs Toth, MD; Yukihiro Yokoyama, MD, PhD; Joachim F. Kuebler, MD; Martin G. Schwacha, PhD; Loring W. Rue III, MD; Kirby I. Bland, MD; Irshad H. Chaudry, PhD

Arch Surg. 2003;138:1375-1382.

Hypothesis  Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock.

Design  Prospective controlled animal study.

Setting  A university laboratory.

Interventions  Female Sprague-Dawley rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which they were resuscitated with Ringer lactate solution (4 x the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity.

Main Outcome Measures  Liver samples were collected for analysis of HO expression and activity, plasma samples were collected, and alanine transaminase levels were determined 5 hours after resuscitation. Portal pressure and bile production were measured in vivo 5 hours after resuscitation.

Results  Trauma and hemorrhage induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in proestrus females compared with males. Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in vivo with tin protoporphyrin IX abolished the sex differences caused by diverse HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal pressure, decreased bile production, and increased alanine transaminase to similar levels in proestrus females and males following trauma and hemorrhage.

Conclusions  Sex influences the hepatic expression of HO1 following trauma and hemorrhage. The enhanced induction of HO1 expression and activity in females after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury by maintaining microcirculation via the increased production of carbon monoxide.

From the Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Haemoglobin expression in human endometrium
Dassen et al.
Hum Reprod 2008;23:635-641.
ABSTRACT | FULL TEXT  

Pharmacological and Clinical Aspects of Heme Oxygenase
Abraham and Kappas
Pharmacol. Rev. 2008;60:79-127.
ABSTRACT | FULL TEXT  

Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway
Kiang et al.
J. Appl. Physiol. 2007;102:933-941.
ABSTRACT | FULL TEXT  

Basal Rather Than Induced Heme Oxygenase-1 Levels Are Crucial in the Antioxidant Cytoprotection
Tsuchihashi et al.
J. Immunol. 2006;177:4749-4757.
ABSTRACT | FULL TEXT  

Maintenance of lung myeloperoxidase activity in proestrus females after trauma-hemorrhage: upregulation of heme oxygenase-1
Yu et al.
Am. J. Physiol. Lung Cell. Mol. Physiol. 2006;291:L400-L406.
ABSTRACT | FULL TEXT  

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression
Szalay et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006;290:R812-R818.
ABSTRACT | FULL TEXT  

PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage
Hsieh et al.
Am. J. Physiol. Heart Circ. Physiol. 2005;289:H2665-H2672.
ABSTRACT | FULL TEXT  

Role of Thromboxane in Producing Hepatic Injury During Hepatic Stress
Yokoyama et al.
Arch Surg 2005;140:801-807.
ABSTRACT | FULL TEXT  

Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: upregulation of heme oxygenase
Szalay et al.
Am. J. Physiol. Heart Circ. Physiol. 2005;289:H92-H98.
ABSTRACT | FULL TEXT  

Mechanism of salutary effects of androstenediol on hepatic function after trauma-hemorrhage: role of endothelial and inducible nitric oxide synthase
Shimizu et al.
Am. J. Physiol. Gastrointest. Liver Physiol. 2005;288:G244-G250.
ABSTRACT | FULL TEXT  

Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage
Shimizu et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004;287:R386-R390.
ABSTRACT | FULL TEXT