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Sex differences in cardiac 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.
2010 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 81, no 12, 1718-1722 p.Article in journal (Refereed) Published
Abstract [en]

Aim of the study: Experimental studies have shown sex differences in haemodynamic response and outcome after trauma and haemorrhagic shock. We recently reported that female sex protects against cerebral injury after exsanguination cardiac arrest (CA), independent of sexual effects of hormones. The current study examines if female sex is also cardioprotective.

Methods: In this study 21 sexually immature piglets (12 males and 9 females) were subjected to 5min of haemorrhagic shock followed by 2min of ventricular fibrillation and 8min of cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3mlkg−1 hypertonic saline-dextran (HSD) solution for 20min. Sexually immature animals were used to differentiate innate sex differences from the effects of sexual hormones. Sex differences in haemodynamics, myocardial injury (troponin I), and short-term survival (3-h) were evaluated.

Results: After resuscitation female animals had a higher blood pressure, lower heart rate, lower troponin I concentrations, and higher survival rate (100% and 63% in 3h) despite comparable sex hormone levels.

Conclusions: After resuscitation from haemorrhage and circulatory arrest, haemodynamic parameters are better preserved and myocardial injury is smaller in female piglets. This difference in outcome is independent of sexual hormones.

Place, publisher, year, edition, pages
2010. Vol. 81, no 12, 1718-1722 p.
Keyword [en]
Cardiopulmonary resuscitation, Haemorrhage, Hypertonic saline, Sex
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-146303DOI: 10.1016/j.resuscitation.2010.08.010ISI: 000285815000023PubMedID: 20817375OAI: oai:DiVA.org:uu-146303DiVA: diva2:397978
Available from: 2011-02-16 Created: 2011-02-16 Last updated: 2017-12-11Bibliographically 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)
Opponent
Supervisors
Available from: 2011-04-08 Created: 2011-02-16 Last updated: 2011-05-05Bibliographically approved

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Semenas, EgidijusWiklund, Lars

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