Neuroprotective effects of 17-beta-estradiol after hypovolemic cardiac arrest in immature piglets: the role of nitric oxide and peroxidation
2011 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 36, no 1, 30-37 p.Article in journal (Refereed) Published
We recently reported that cerebral and cardiac injuries are mitigated in immature female piglets after severe hemorrhage with subsequent cardiac arrest (CA) Female sex was also associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (nNOS). In the current study, we tested the hypothesis that exogenously administered 17β-estradiol (E2) can improve neurological outcome by NOS modulation. Thirty nine sexually immature piglets were bled to a mean arterial pressure of 35 mmHg over 15 min. Fifty μg/kg of E2 was then administered to 10 male and 10 female animals (estradiol group), while control animals (n=10 males and 9 females) received equal volume of normal saline. The animals were then subjected to ventricular fibrillation (4 min) followed by up to 15 min of open chest CPR. Vasopressin 0.4 U/kg and amiodarone 0.5 mg/kg were given and 3 ml/kg of 7.5% saline with 6% dextran was administered over 20 min. All surviving animals were euthanized after 3hr and their brains examined for histological injury and NOS expression. No significant differences were observed in survival or hemodynamics between the groups. 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 a significant correlation between nNOS and iNOS levels and neuronal injury. Interestingly estradiol attenuated cerebral damage (including lower activation of nNOS and iNOS) both in male and female piglets. In conclusion, in our immature piglets model of hypovolemic cardiac arrest, E2 down-regulates iNOS and nNOS expression and results in decreased BBB permeability disruption and smaller neuronal injury.
Place, publisher, year, edition, pages
2011. Vol. 36, no 1, 30-37 p.
Cardiac and Cardiovascular Systems Surgery Anesthesiology and Intensive Care
IdentifiersURN: urn:nbn:se:uu:diva-146312DOI: 10.1097/SHK.0b013e3182150f43ISI: 000291675800006PubMedID: 21330940OAI: oai:DiVA.org:uu-146312DiVA: diva2:397986