Inhaled nitric oxide in combination with volume resuscitation refines a porcine model of endotoxic shock.
BACKGROUND
Existing porcine models of endotoxic shock poorly represent the human situation.


OBJECTIVE
To assess whether the cardiovascular profile of a porcine model could be improved by refining the protocol.


METHODS
In 30 pigs, right and left heart pressures and cardiac output were measured. Lipopolysaccharide (LPS) was administered as a bolus (n=12), as a 30 minute infusion (n=6) or as a 30 minute infusion along with inhaled NO and volume resuscitation (n=6) and six sham-treated pigs received normal saline. Haemodynamic values were measured over three hours.


RESULTS
LPS increased pulmonary vascular resistance (PVR) (13.3 +/- 1.4 to 37.0 +/- 3.9kPa/l per sec, p<0.05) and reduced cardiac output (6.0 +/- 0.6 to 4.8 +/- 0.41/min). Mortality was 50% within 30 minutes. Inhaled NO and volume resuscitation controlled pulmonary vascular resistance (PVR) and preserved CO. Systemic vascular resistance (SVR) declined in the first hour (118.4 +/- 11.8 to 65.8 +/- 8.2kPa/l per sec, p<0.05) and remained low.


CONCLUSIONS
Porcine models of endotoxaemia based on LPS administration are a poor model of human septic shock, but can be improved by regulating PVR and supporting CO which may contribute to future studies of septic shock
Herity
N A
NA
Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, Northern Ireland. nherity@cahgt.n-i.nhs.uk
Allen
J D
JD
Silke
B
B
Adgey
A A
AA
D000280:Administration, Inhalation; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D012772:Shock, Septic / Q000503:physiopathology / Q000628:therapy*; D013552:Swine
D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide