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Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
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2010 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 54, no 3, 343-353 p.Article in journal (Refereed) Published
Abstract [en]

Background: Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre-pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid. Methods: Thirty-two sexually immature piglets (14 males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using three resuscitation fluid regimens (whole blood, hypertonic saline and dextran, or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic values, cellular markers of brain injury and brain histology were studied. Results: After successful resuscitation, female piglets had significantly greater cerebral cortical blood flow, tended to have lower S-100beta values and a lower cerebral oxygen extraction ratio. Besides, in female animals, systemic and cerebral venous acidosis were mitigated. Female piglets exhibited a significantly smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in their cerebral cortex, smaller blood-brain-barrier (BBB) disruption and significantly smaller neuronal injury. Conclusion: After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is greater, and BBB permeability and neuronal injury is smaller in female piglets. An increased cerebral cortical iNOS and nNOS expression in males implies a mechanistic relationship with post-resuscitation neuronal injury and warrants further investigation.

Place, publisher, year, edition, pages
2010. Vol. 54, no 3, 343-353 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-122756DOI: 10.1111/j.1399-6576.2009.02125.xISI: 000274313000012PubMedID: 19764903OAI: oai:DiVA.org:uu-122756DiVA: diva2:310946
Available from: 2010-04-19 Created: 2010-04-19 Last updated: 2015-06-08Bibliographically approved
In thesis
1. Sex Differences in Cardiac and Cerebral Damage after Hypovolemic Cardiac Arrest
Open this publication in new window or tab >>Sex Differences in Cardiac and Cerebral Damage after Hypovolemic Cardiac Arrest
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Resuscitation from haemorrhagic shock and the subsequent circulatory arrest remains a major clinical challenge in the care of trauma patients. Numerous experimental studies in sexually mature animals have shown a gender dimorphism in response to trauma and haemorrhagic shock. The first study was designed to evaluate sex differences in outcome after resuscitation from hypovolemic circulatory arrest. We intended to examine innate sex differences, and chose to study sexually immature animals. The study showed that cerebral cortical blood flow was greater, blood-brain-barrier was better preserved and neuronal injury was smaller in female as compared to male piglets. The second study demonstrated that female sex was associated with enhanced haemodynamic response, cardioprotection, and better survival. This cardioprotective effect was observed despite comparable estradiol and testosterone levels in male and female animals, indicating an innate gender-related cardioprotection. In both studies (I and II) female sex was associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (iNOS and nNOS). Thus in the study III we tested the hypothesis that exogenously administered 17β-estradiol (E2) could improve neurological outcome by NOS modulation. The results showed that compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was also a significant correlation between nNOS and iNOS levels and neuronal injury. A hypothesis if female-specific cardioprotection may be attributed to a smaller NOS activity was tested in study IV. The animals received methylene blue (MB) during CPR, but were otherwise treated according to the same protocol as studies I-II. The female-specific cardioprotection could be attributed to a smaller NOS activity, but NOS inhibition with MB did not improve survival or myocardial injury, although it abated the difference between the sexes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 654
Keyword
Cardiopulmonary resuscitation, sex, haemorrhage, neuronal damage, estradiol, hypertonic saline, nitric oxide, methylene blue
National Category
Medical and Health Sciences
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-146314 (URN)978-91-554-8028-8 (ISBN)
Public defence
2011-04-28, Hedstrandsalen, Akademiska sjukhuset, entrance no. 70, Uppsala, 09:15 (Swedish)
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Available from: 2011-04-08 Created: 2011-02-16 Last updated: 2011-05-05Bibliographically approved

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Semenas, EgidijusSharma, Hari ShankerRubertsson, StenWiklund, Lars

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