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 (R1), vascular compliance (C), input resistance (R2) 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 R1 (from 0.04 +/- 0.01 to 0.06 +/- 0.01 mm Hg s ml-1) and R2 (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.
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D011652:Pulmonary Circulation / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects