Bleeding, hypothermia, acidosis and the normal ROTEM®

shock (HS) and acute pancreatitis (AP) is associated with multiple organ dysfunction syndrome (MODS) and death. Most common in MODS are cardiac and pulmonary dysfunction.The ‘gut-lymphhypothesis’ states thatMODSisdue to the releaseof toxic factors fromthe intestine intomesenteric lymph (ML). Significant composition changes to ML are associated with acute pancreatitis and other CI’s. ML is delivered to the systemic circulation via the thoracic duct and en route bypasses the liver avoidingpotential detoxification, beforefirst encountering the heart and then lungs. The aim of this study was to determine the effect of HS and AP conditioned ML on cardiac function and the effect of external drainage of ML. Methods: Groups (n=8 / group) of normal rats and those with taurocholate induced severe AP, a model of critical illness, had either no lymphatic intervention or thoracic duct (TD) ligation with external ML drainage (to protect the hearts from exposure to ML). After 6 hours the heart was removed from both groups for ex vivo functional measurements, including cardiac output and ventricular contractility (+dP/dt), relaxation (-dP/dt). In a separate experiment ML was collected from normal rats and those with HS and AP and infused into ex vivo perfused working hearts from donor normal rats to assess the impact on cardiac function. Results: Significant cardiac dysfunction was found in the hearts removed from rats with established AP alone (no lymphatic intervention) compared to the control group (p<0.05). Strikingly this dysfunction did not occur in rats with established AP and TD ligation with ML drainage. In the second experiment infusion of HS and AP conditioned ML resulted in an immediate, similar and significant reduction of cardiac output (p< 0.05) with corresponding significant reductions in the measures of cardiac contractility and relaxation (p<0.05) compared with normal lymph. Discussion:HS and AP conditioned ML causes significant cardiac dysfunction which can be prevented by TD ligation and external ML drainage. This cardio-depressant effect is likely to be important in other CI’s. The nature of the mediators in ML is still speculative but likely to be gut and pancreas derived serine proteases. The findings from this study have future implications in how we treat cardiac dysfunction and failure in critically ill patients.