The effects of activated protein C and prostacyclin on arterial oxygenation and protein leakage in the lung and the gut under endotoxaemia in the rat.
BACKGROUND
Based on the anti-adhesive/anti-aggregatory and permeability-reducing properties of activated protein C (APC) and prostacyclin (PGI(2)), we analysed and compared these substances regarding their efficacy in counteracting transcapillary leakage of albumin in the lung and the gut, and in improving arterial oxygenation under a condition of inflammation.


METHODS
The randomized and blinded study was performed on 31 adult male Sprague-Dawley rats. Inflammation was induced by continuous infusion of Escherichia coli endotoxin (lipopolysaccharide, LPS). Six hours after the start of the LPS infusion (240,000 U/kg/h), a simultaneous infusion of saline (control group) or 8 microg/kg/min of human recombinant APC or 2 ng/kg/min of PGI(2) was started and continued for 24 h (n=8 per group). The study also included a sham group. Transcapillary leakage of albumin was measured from the ratio between tissue radioactivity [counts per minute (cpm)/g tissue] and actual amount of radioactivity given (cpm/g body weight of (125)I-albumin). Oxygenation was assessed from arterial and central venous blood samples.


RESULTS
LPS induced albumin leakage in the gut and the lung, and impaired blood oxygenation. In the lung, the leakage was lower in the PGI(2) group than in the APC and the control groups (P<0.05). In the gut, it was lower in the APC and the PGI(2) groups than in the control group (P<0.05). Oxygenation was better in the APC and PGI(2) groups than in the control group.


CONCLUSIONS
Our data suggest that both APC and low-dose PGI(2) are beneficial in LPS-induced inflammation in the rat, by reducing albumin leakage and improving blood oxygenation.
Dubniks
M
M
Department of Anaesthesiology and Intensive Care, Lund University and Lund University Hospital, Lund, Sweden. maris.dubniks@med.lu.se
Grände
P-O
PO
D000418:Albumins; D000818:Animals; D019559:Capillary Leak Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced; D007410:Intestinal Diseases / Q000517:prevention & control*; D008171:Lung Diseases / Q000517:prevention & control*; D008297:Male; D010100:Oxygen / Q000097:blood; D011486:Protein C / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D000418:Albumins; D004731:Endotoxins; D011486:Protein C; D011994:Recombinant Proteins; C044101:endotoxin, Escherichia coli; D011464:Epoprostenol; D010100:Oxygen