Different Serotypes Of Endotoxin (Lipopolysaccharide) Cause Different Increases in Albumin Extravasation in Rats

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Abstract
Endotoxin (lipopolysaccharide [LPS] from cell membranes of gram-negative bacteria) is frequently used in experimental models of septic shock that are characterised by hypotension, peripheral vasodilation, and edema formation, as well as greatly enhanced flux of macromolecules and fluid from plasma to tissues. The edema formation and increased albumin extravasation (Ealb) could be caused by increased permeability and/or increased capillary net filtration pressure. We have measured interstitial fluid pressure (Pif) and Ealb after i.v. injection of two different serotypes of LPS in female Wistar Møller rats (200-250 g) in pentobarbital anaesthesia. Two experimental groups and one control group were studied (n = 8 in each group). Group 1, serotype 0111:B4, received 3 mg/kg LPS, Group 2, serotype 0127:B8, received 1.5 mg/kg LPS, and controls received saline vehicle (0.4 mL). Five minutes after injection of LPS or saline vehicle, human serum albumin labelled with 125I (125I-HAS; 0.05 MBq) was injected i.v. and was followed 55 min later by 131I-HSA (0.05 MBq). Five minutes thereafter the rats were killed and tissue samples were obtained from skin, muscle, and small intestine. Ealb was estimated as the difference between the plasma equivalent distribution volumes of 125I-HSA and 131I-HSA. The pattern of extravasation between the groups was the same in all the tissues studied. Group 1 serotype (0111:B4) and controls had much lower Ealb than Group 2 serotype (0127:B8; P < 0.05). Ealb differed among the tissues both in relative and absolute numbers, being largest in the intestine and smallest in skeletal muscle. We previously demonstrated a lowering of Pif after LPS injection using serotype (0127:B8). The present results demonstrate that the same serotype of LPS also causes a significant increase of Ealb, and is therefore likely caused by the lowering of Pif.