MassTrace and its academic collaborators (Sims, et al.) has demonstrated in pilot studies that intravenous pyruvate ethyl ester prevents mucosal injury of the rat small intestine following ischemia-reperfusion, more effectively than lactic acid or pyruvic acid in a Ringer's solution. Esterified carboxylic acids, structurally related to pyruvate, can form stable solutions in the presence of calcium (or magnesium) ions and can be expected to cross cell membranes more easily than their free acids. We propose to investigate the effects of intravenous pyruvate ethyl ester Ringer's (PER) as a resuscitative fluid with three (3) questions in mind: (1) What are the physico-chemical properties of PER responsible for its effect? (2) How do these properties influence the mechanism of action of PER and its structural analogs in in vitro model biochemical systems? (3) Does intravenous PER protect the intestinal mucosal barrier better than other closely related structural analogs following hemorrhagic shock? If PER Ringer's proves to be an effective and protective resuscitative fluid, it could change the way in which patients are initially treated following traumatic insult or how they are maintained during ischemia and reperfusion. PROPOSED COMMERCIAL APPLICATIONS: Our business objective is to introduce a novel pharmacologic treatment, formulated as a Ringer's substitute, for use in resuscitation and reanimation before, during and after (1) mesenteric ischemia, (2) aortic aneurism repair, (3) hemorrhagic shock. Commercial applications also might be anticipated in (4) coronary infusion through coronary arteries after angioplasty and stenting and (5) in the preservation of organs before transplantation
