Perfusion Medical is commercializing a novel pipeline product called PEG-20k IV Solution. The company believes this may be the first therapeutic to directly treat lethal complications of sepsis, and as such, support new thinking on the basic mechanisms of the disease. Sepsis or septic syndrome leads to a spectrum of illnesses and occurs at a frequency of 1.7 million people in the US each year and septic shock kills over 270,000 Americans each year. Sepsis, caused by direct bacterial infection or by leak of lipopolysaccharide (LPS) from a compromised splanchnic circulation, produces a complex cascade of immunological and non-immunological reactions. These ultimately lead to multiple systems organ failure and death. There are no medications specifically used to mitigate any underlying basis for sepsis other than infection and source control. The company asserts that the combination of restoration of tissue perfusion in early sepsis and breaking down endothelial cell glycocalyx, will be a radically new approach that prevents the vicious cycle and the attendant fatal multiple organ failure. The STTR involves two AIMS. AIM 1 will determine regional capillary perfusion in LPS-induced and polymicrobial peritonitis-induced septic shock and the effects of PEG-20k resuscitation. The researchers will seek to demonstrate that the massive perfusion defect associated with LPS or bacterial sepsis is reversed by PEG-20k IV solution and that restoring perfusion in early course of sepsis averts multiple organ failure and mortality by preserving vital tissue oxygen exchange. AIM 2 will determine the integrity of the glycocalyx in sepsis and the effect of PEG-20k resuscitation. The team intends to demonstrate that PEG-20k nonspecifically binds to and protects / rebuilds the endothelial glycocalyx during sepsis and multiple organ failure, which limits secondary cellular inflammatory end-organ injury. At the end of this study, the company will have proof-of-concept data showing that a major determinant of septic shock mortality and organ failure is secondary to severe malperfusion of vital tissues and that early correction with PEG-20k can avert devastating downstream consequences leading to critical illness and death. If successful, the solution will be shown to be effective with two mechanisms of addressing sepsis – either of which will make PEG-20k a strong candidate as a therapeutic product.