Hepatic and intestinal microcirculation and pulmonary inflammation in a model of veno-venous extracorporeal membrane oxygenation in the rat

Abstract

Background: Veno-venous (V–V) extracorporeal membrane oxygenation (ECMO) is widely used in critical care but remains associated with high mortality rates (22–68%). In septic shock, increased pulmonary inflammation and impaired intestinal and hepatic microcirculation have been observed during ECMO therapy. To explore the impact of ECMO-induced inflammation, this study used a rat model with varying ECMO blood flows to assess intestinal and hepatic microcirculation and lung inflammation.

Methods:Thirty male Lewis rats were randomised into three groups: sham, low-flow ECMO (60 mL/kg/min), and high-flow ECMO (90 mL/kg/min). V–V ECMO was established via femoral drainage and jugular return. Microcirculation in the intestine and liver was measured using micro-light guide spectrophotometry after laparotomy. Systemic and pulmonary inflammation were evaluated through cytokine levels in plasma and bronchoalveolar lavage (BAL), focusing on tumour necrosis factor-alpha (TNF-α), interleukins 6 (IL6) and 10 (IL10), and C–X–C motif chemokine ligands 2 (CXCL2) and 5 (CXCL5). Hemodynamic data were obtained using a left ventricular pressure–volume catheter.

Results: Intestinal oxygenation was significantly impaired only during low-flow ECMO therapy (65% [62–70%]) compared to sham therapy (76% [72–79%], p = 0.003), while hepatic microcirculation was reduced during both low-flow (21% [14–26%]) and high-flow (19% [16–21%]) ECMO therapy compared to sham therapy (43% [38–48%], all p < 0.001). Serum TNF-α levels were only significantly elevated during high-flow ECMO therapy (1 h: 14 [12–22] pg/mL; 2 h: 18 [15–38] pg/mL) compared to the sham procedure (1 h: 10 [9–11] pg/mL; 2 h: 10 [9–11] pg/mL; p = 0.033). In contrast, BAL IL6 levels were significantly lower during both high- and low-flow ECMO therapy (32 pg/mL) than sham therapy (81 pg/mL, p ≤ 0.001). IL10, CXCL2, and CXCL5 levels did not differ significantly between the low- and high-flow ECMO and sham therapies.

Conclusions: ECMO-induced inflammation is blood flow dependent. In healthy rats, high-flow ECMO did not impair intestinal microcirculation and was associated with reduced pulmonary inflammation, likely due to lung-protective ventilation.