Never Change a Flowing System? The Effects of Retrograde Flow on Isolated Perfused Lungs and Vessels.

Retrograde perfusion may occur during disease, surgery or extracorporeal circulation. While it is clear that endothelial cells sense and respond to changes in blood flow, the consequences of retrograde perfusion are only poorly defined. Similar to shear stress or disturbed flow, retrograde perfusion might result in vasomotor responses, edema formation or inflammation in and around vessels. In this study we investigated in rats the effects of retrograde perfusion in isolated systemic vessels (IPV) and in pulmonary vessels of isolated perfused lungs (IPL). Anterograde and retrograde perfusion was performed for 480 min in IPV and for 180 min in the IPL. Perfusion pressure, cytokine levels in perfusate and bronchoalveolar lavage fluid (BALF), edema formation and mRNA expression were studied. In IPV, an increased perfusion pressure and initially also increased cytokine levels were observed during retrograde perfusion. In the IPL, increased edema formation occurred, while cytokine levels were not increased, though dilution of cytokines in BALF due to pulmonary edema cannot be excluded. In conclusion, effects of flow reversal were visible immediately after initiation of retrograde perfusion. Pulmonary edema formation was the only effect of the 3 h retrograde perfusion. Therefore, further research should focus on identification of possible long-term complications of flow reversal.

The pro-inflammatory stimulus of zinc- and copper-containing welding fumes in whole blood assay via protein tyrosine phosphatase 1B inhibition.

An asymptomatic systemic inflammation after exposure to zinc- and copper-containing welding fumes has been described as mild form of metal fume fever in recent studies. Since chronic systemic inflammation leads to a higher cardiovascular risk, examining the inflammation with the underlying pathomechanism is necessary to estimate and hopefully prevent long-term effects of welding. We established a whole blood assay to investigate the effects of zinc- and copper-containing welding fume particles on the blood immune response. Increased levels of IL-6, IL-8, TNFα and IL-1ß determined after 24 hours of exposure indicated an acute systemic inflammatory reaction. In vitro increases of IL-6 were comparable to in vivo increases of serum IL-6 levels in a study with welding fume exposure of human subjects. Inhibition of PTP1B was identified as one pathway responsible for the effects of zinc- and copper-containing welding fumes and therefore welding fume fever. In conclusion, the whole blood assay is a reliable and feasible method to investigate effects of zinc- and copper-containing welding fumes on the immune system and as a surrogate for systemic inflammation and welding fume fever. Future research can utilize whole blood assays to reduce and partially replace human exposure studies for further investigations of welding fume fever.