The effects of hydroxyethyl starch and gelatine on pulmonary cytokine production and oedema formation

Abstract

Recently, side effects of plasma expanders like hydroxyethyl starch and gelatine gained considerable attention. Most studies have focused on the kidneys; lungs remain unconsidered. Isolated mouse lungs were perfused for 4 hours with buffer solutions based on hydroxyethyl starch (HES) 130/0.4, HES 200/0.5 or gelatine and ventilated with low or high pressure under physiological pH and alkalosis. Outcome parameters were cytokine levels and the wet-to-dry ratio. For cytokine release, murine and human PCLS were incubated in three different buffers and time points.In lungs perfused with the gelatine based buffer IL-6, MIP-2 and KC increased when ventilated with high pressure. Wet-to-dry ratios increased stronger in lungs perfused with gelatine - compared to HES 130/0.4. Alkalotic perfusion resulted in higher cytokine levels but normal wet-to-dry ratio. Murine PCLS supernatants showed increased IL-6 and KC when incubated in gelatine based buffer, whereas in human PCLS IL-8 was elevated. In murine IPL HES 130/0.4 has lung protective effects in comparison to gelatine based infusion solutions, especially in the presence of high-pressure ventilation. Gelatine perfusion resulted in increased cytokine production. Our findings suggest that gelatine based solutions may have side effects in patients with lung injury or lung oedema.

Retrograde perfusion in isolated perfused mouse lungs—Feasibility and effects on cytokine levels and pulmonary oedema formation

“…Thus, no considerable crosstalk between vascular and airway department seems to be induced by retrograde perfusion. The time course of perfusate cytokines over 4 hours of IPL has been described before . IL‐6, KC and MIP‐2 levels increase over the 4 hours with higher levels in OV compared to NV.…”

“…The time course of perfusate cytokines over 4 hours of IPL has been described before. 27 IL-6, KC and MIP-2 levels increase over the 4 hours with higher levels in OV compared to NV. Thus, the comparison of levels after 240 minutes of ventilation and perfusion is suitable.…”

“…Non‐recirculating perfusion anterogradely via pulmonary artery and left ventricle or retrogradely via left ventricle and right pulmonary artery was performed at 0.5 mL/min resulting in a pulmonary inflow perfusion pressure of 0.5 up to 4 cmH 2 O. The perfusing buffer contained polysuccinated bovine gelatin and was added with various supplements including sodium phosphate and sodium hydrogen carbonate as described before …”

“…The perfusing buffer contained polysuccinated bovine gelatin and was added with various supplements including sodium phosphate and sodium hydrogen carbonate as described before. 27 Based on random allocation, mice received either NV or OV and either anterograde or retrograde perfusion. Retrograde F I G U R E 1 The IPL system: flow and cannulation in anterograde and retrograde perfusion.…”

Point-of-Care Ultrasound—A New Option for Early Quantitative Assessment of Pulmonary Edema

“…The actions of IL-1b and TNF-a increase chemotaxis and activation of the neutrophils, stimulate the secretion of inflammatory mediators and oxygen free radicals by the pulmonary vascular endothelial cells and increase the permeability of the pulmonary vascular system by activating the coagulation system and inhibiting the fibrinolytic system in the early stage of lung inflammatory reactions (Howrylak and Nakahira 2017;Malaviya et al 2017). IL-6 and IL-8, secreted mainly by lymphocytes, macrophages and endothelial cells, play an important role in the formation and development of acute inflammatory reactions in lung tissue (Krabbe et al 2018;Rose-John 2018). Therefore, under the stimulation of the inflammatory injury initiation factors, TNF-a and IL-1b are rapidly secreted by lung tissues.…”