Analysis of endotoxin effects on the intact pulmonary circulation

Objective: The mechanism of sustained alterations in pulmonary hemodynamics during endotoxin shock remains unclear. To gain more detailed knowledge we used the four-element windkessel model as a descriptor of the pulmonary circuit. Methods: Consecutive changes in characteristic resistance (R-1), vascular compliance (C), input resistance (R-2) and inductance (L) were continuously assessed following injection of endotoxin in 6 anaesthetised pigs, and were compared with the corresponding values measured in a similar group of sham-operated animals. Results: Endotoxin challenge resulted in a biphasic pulmonary artery pressure response. Blood flow decreased progressively from 2.8+/-0.2 l/min to 2+/-0.2 l/min. Ohmic pulmonary vascular resistance (PVR) increased gradually from 0.2+/-0.04 to 0.76+/-0.1 mm Hg s ml(-1). The early increase in PAP (from 14+/-2 to 27+/-4 mm Hg) was mediated by changes in both R-1 (from 0.04+/-0.01 to 0.06+/-0.01 mm Hg s ml(-1)) and R-2 (from 0.16+/-0.04 to 0.61+/-0.2 mm Hg s ml(-1)). These responses, in turn, altered the proximal vascular compliance. A subsequent increase in PAP (from 27+/-2 to 32+/-3 mm Hg) paralleled the specific decline in distal pulmonary vasculature compliance from 0.84+/-0.1 to 0.65+/-0.1 ml/mmHg. Analysis of the time course of PVR did not allow us to distinguish between vasoconstriction and stiffening of the vascular tree as mechanisms accounting for PAP changes. Conclusions: Endotoxemia leads to pulmonary hypertension, which is a result of constriction of proximal pulmonary arteries during the early phase, whereas the late phase is characterised by a decline in distal pulmonary vasculature compliance. (C) 1999 Elsevier Science BN. All rights reserved.