Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs.
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.


CONCLUSIONS
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.
Semenas
E
E
Department of Surgical Sciences/Anesthesiology and Intensive Care, Faculty of Medicine, Uppsala University Hospital, S-751 85 Uppsala, Sweden. egidijus.semenas@gmail.com
Nozari
A
A
Sharma
H S
HS
Basu
S
S
Rubertsson
S
S
Wiklund
L
L
D000136:Acid-Base Equilibrium / Q000502:physiology; D000418:Albumins / Q000378:metabolism; D000768:Anesthesia, General; D000818:Animals; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D005440:Fluid Therapy; D012739:Gonadal Steroid Hormones / Q000097:blood; D006439:Hemodynamics / Q000502:physiology; D006470:Hemorrhage / Q000150:complications* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D012151:Resuscitation; D012212:Rheology; D009418:S100 Proteins / Q000378:metabolism; D012727:Sex Characteristics; D013534:Survival; D013552:Swine; D016707:Tissue Fixation; D014693:Ventricular Fibrillation / Q000150:complications* / Q000473:pathology
D000418:Albumins; D012739:Gonadal Steroid Hormones; D009418:S100 Proteins; D019001:Nitric Oxide Synthase; D010100:Oxygen