Hepatic influence on pulmonary neutrophil sequestration following intestinal ischemia-reperfusion.

Intestinal ischemia-reperfusion (I/R) causes a myriad of systemic physiologic derangements including pulmonary neutrophil (PMN) sequestration, increased microvascular permeability, and adult respiratory distress syndrome. It has been suggested that the observed lung injury is mediated by transhepatic passage of portal venous blood from ischemic intestine resulting in hepatic Kupffer cell activation and cytokine secretion. The purpose of this investigation was to test the hypothesis that PMN sequestration and microvascular permeability reflect Kupffer cell activity and/or portal venous blood flow. Experiments were designed to independently test the contribution of (1) Kupffer cell activity and (2) portal venous blood flow. In the first set of experiments, Kupffer cells were eliminated by treatment with gadolinium chloride 10 mg/kg iv (KC-ablated, n = 11). Control rats were treated with saline (KC-intact, n = 10). Intestinal ischemia was induced by SMA occlusion for 2 hr followed by 2 hr of reperfusion. In additional studies, the liver was excluded from the circulation by creation of a complete portosystemic shunt (portal vein to right femoral vein; shunt, n = 23). Control rats were treated by insertion of a loop of tubing within the intact portal vein (sham, n = 23). Intestinal ischemia was induced by SMA occlusion for 15 min followed by reperfusion for 1-3 hr. In both models, lung PMN accumulation and pulmonary microvascular permeability were assessed by myeloperoxidase (MPO) activity and 125I-albumin lung/blood ratio (AL/BR), respectively. Kupffer cell elimination had no effect on PMN accumulation (MPO: KC-intact 29 +/- 8 vs KC-ablated 26 +/- 5 delta A/min/g; P = NS) or microvascular permeability (AL/BR: KC-intact 0.22 +/- 0.01 vs KC-ablated 0.23 +/- 0.03; P = NS). Hepatic exclusion also had no effect on either PMN accumulation or permeability after reperfusion for 1 hr (MPO: sham 38 +/- 12 vs shunt 42 +/- 14 delta A/min/ g; AL/BR: sham 0.24 +/- 0.02 vs shunt 0.23 +/- 0.03; P = NS), 2 hr (MPO: sham 27 +/- 5 vs shunt 29 +/- 7 delta A/min/g; AL/ BR: sham 0.29 +/- 0.02 vs shunt 0.26 +/- 0.05; P = NS), or 3 hr (MPO: sham 24 +/- 12 vs shunt 32 +/- 7 delta A/min/g; AL/ BR: sham 0.33 +/- 0.03 vs shunt 0.33 +/- 0.01; P = NS). In this animal model, pulmonary PMN sequestration and microvascular permeability following intestinal I/R are independent of hepatic portal blood flow and Kupffer cell activity.