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
Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, Northern Ireland. nherity@cahgt.n-i.nhs.uk
N A
NA
Herity
J D
JD
Allen
B
B
Silke
A A
AA
Adgey
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