PULMONARY DAMAGE AFTER RECURRENT ADMINISTRATION OF ENDOTOXIN AND ZYMOSAN-ACTIVATED PLASMA - A SHEEP MODEL

We compared the effects of chronic complement stimulation by intermitt ent i.v. bolus of endotoxin and zymosan-activated plasma (ET/ZAP, 0.75 mug/kg body wt. and 20 ml ZAP, group 1, n = 7) or endotoxin (ET, 1 mu g/kg body wt., group 2, n = 13) on lung function and pulmonary and sys temic hemodynamics. Twenty adult female merino sheep received intraven ous bolus injections twice daily, 12 h apart, for 5 consecutive days. Bronchoalveolar lavage fluid (BAL) was obtained before the first (day 1), fifth (day 3), and ninth (day 5) endotoxin injection. PMN as well as macrophages were sampled from central venous blood and from BAL for measurement of respiratory burst activity (chemiluminescence). A comp arable septic haemodynamic response was present in both groups. The ch emiluminescence of systemic PMN did not increase in the late stage in either group. Systemic oxygenation (PaO2) deteriorated significantly i n ET/ZAP animals (group 1) at day 5 compared with ET animals (group 2) (group 1: 88 +/- 4 mmHg, group 2:72 +/- 6 mmHg, (P < 0.05)). Pulmonar y permeability as determined by the epithelial lining fluid (ELF) / pl asma ratio of albumin was worse in ET/ZAP animals at day 5 (da 1: 0.08 +/- 0.06 in group 1; 0.05 +/- 0.01 in group 2), (day 5: 0.29 +/- 0.07 in group 1, 0.08 +/- 0.06) (P < 0.05). Alveolar macrophages (AMo) sho wed significantly more respiratory burst activity in ET/ZAP animals at day 5 than in ET animals (393 +/- 21 X 10(3)cpm/25 000 AMo in group 1 , 123 +/- 29 X 10(3)cpm/25 000 AMo in group 2, (P < 0.05). Additional intravenous ZAP leads to late pulmonary dysfunction in the absence of more systemic dysfunction compared with ET only. Next to known effects of activated neutrophils in complement-induced pulmonary injury, macr ophage stimulation also might play a role.