Microcirculation changes following acute and chronic portal hypertension and their response towards bacterial translocation challenge

Background

Patients with cirrhosis have higher risk of infection and multiorgan dysfunction syndrome. Increasing evidence relates them to the higher susceptibility to bacterial translocation (BT) by liver dysfunction and hemodynamic changes. Herein, we evaluated the role of BT in acute and chronic portal hypertension (a-PH and c-PH) states without cirrhoses.

Methods

Forty-eight Wistar rats were distributed in BT, a-PH, c-PH with/without BT and control groups. a-PH (minimal shunting) and c-PH (extensive shunting) were induced by calibrated portal vein stenosis and were submitted to BT on days 2 and 14, respectively, by oroduodenal inoculation (10 ml Escherichia coli R-6, 10⁷ or 10¹⁰ colony-forming units (CFU)/ml) and confinement into the small bowel for 2 hours. BT-sham (saline), PH-sham (without portal stenosis), and PH groups were monitored for splachnic (liver, spleen, ileum) and kidney perfusion by laser Doppler, and mesenteric lymph node (MLN), liver, spleen, lung, blood and peritoneal fluid (PF) samples were cultured.

Results

In the BT 10¹⁰ group, the culture was 100% positive at the MLN, liver and spleen (5.3 and 3 log₁₀ CFU/g, respectively), while the blood, PF and lung were negative. In a-PH animals, the BT 10¹⁰ pattern was 100% to the MLN, liver and spleen (5.4 and 4 log₁₀ CFU/g, respectively), lung (100%, 3 log₁₀, P < 0.05) and PF (10%, 0.6 log₁₀). In turn, c-PH-BT10¹⁰ findings were similar to BT10¹⁰ alone but there was an increased translocation to PF (40%, 1 log₁₀, P < 0.05). On the other hand, for BT 10⁷ all cultures were negative, but in PH-BT10⁷ translocation occurred to the MLN (a-PH 50%, 1 log₁₀ CFU/g; c-PH 25%, 0.7 log₁₀ CFU/g) plus to the PF (a-PH 12.5%, 0.08 log₁₀ CFU/g; c-PH 25%, 0.16 log₁₀ CFU/g), evidencing a change in the gut threshold for BT in the PH state. Bacterial challenge in the a-PH state showed that the liver, spleen and kidney go into a hypoperfusion state (-38, -45.2 and -36 Δ%, respectively), in contrast to the ileum hyperperfusion response (+75 Δ%). Similarly, at c-PH the liver and kidney maintained a hypoperfusion state (-17%, -33% Δ%). Based on both saline-PH groups' data, however, the ileum and liver microcirculation functional adaptation was mostly compromised only at the chronic phase.

Conclusion

Portal hypertension factor without cirrhosis increases and changes the pattern of BT, especially to the lung at a-PH and to the PF at c-PH states, under small bowel Gram-negative bacterial overgrowth conditions. These findings, in addition to the tissue perfusion impairment, might explain the higher susceptibility to infection in portal hypertension diseases.