Extracorporeal circulation exacerbates microvascular permeability after endotoxemia.
BACKGROUND: Extracorporeal life support without prior inflammatory stimuli results in a modest increase in microvascular permeability. Initiating ECLS after shock, sepsis, or hypoxia results in marked increases in interstitial fluid and total body water. We sought to determine whether an inflammatory stimulus prior to initiating ECLS increases microvascular permeability to protein. METHODS: An anesthetized canine lymphatic fistula model was used to study Starling forces. LPS + ECLS received 1 mg/kg LPS 1 h prior to initiating ECLS, and the group ECLS received saline vehicle. To determine mesenteric microvascular permeability, mesenteric venous pressure was elevated to 32 +/- 1 mm Hg to reach a minimal lymph protein concentration (C(L)). With simultaneous measurement of plasma protein concentration (C(P)), the reflection coefficient, sigma, was calculated using the formula sigma = 1 - C(L)/C(P). Transvascular protein clearance and filtration coefficient (K(f)) were calculated from the measured Starling variables. After a steady state was achieved, normothermic right atrial-to-femoral artery ECLS was initiated and continued for 2 h and then discontinued. Measurements were continued for 30 min after ECLS was discontinued. Measurements were continued for 30 min after ECLS was discontinued. Within-group comparisons were made with ANOVA and Fisher's LSD, and between-group comparisons were made with Student's t tests where appropriate. RESULTS: The reflection coefficient (sigma) decreased significantly from 0.77 +/- 0.02 to 0.53 +/- 0.07 with LPS + ECLS and was lower compared to ECLS alone (0.77 +/- 0.02 to 0.65 +/- 0.03). Transvascular protein clearance increased to a greater extent in LPS + ECLS from 266 +/- 46 to 819 +/- 125 microl/min compared to ECLS alone (284 +/- 49 to 819 +/- 125 microl/min) (P = 0. 06). K(f) increased in both groups after initiation of ECLS, but to a significantly greater extent in LPS + ECLS at 60 min (30.7 +/- 2.2 microl/min/mm Hg/g in ECLS and 50.0 +/- 8.9 microl/min/mm Hg/g in LPS + ECLS). Ileal tissue water increased in both groups, but there were no differences between groups. CONCLUSIONS: Initiation of ECLS after exposure to LPS increases ileal microvascular permeability to protein and water to a greater extent than ECLS alone.