FIGURE 3.

Systems Hypothesis Of Trauma (SHOT) showing key inter-connected sites of uncoupling during early and late deaths: (1) brain, (2) heart, (3) vasculature, (4) endothelial-glycocalyx-mitochondrial unit, and (5) gut barrier breaches. Our hypothesis is that if central and local control of cardiac output and ventriculo-arterial (VA) coupling are improved, endothelial and microvascular function will be improved and tissue O₂ delivery will be maintained. An uncoupling is reflected by an increase in stress hormones, sympathetic discharge, loss of baroreceptor sensitivity, reduced heart rate variability (183, 184), unresolved inflammation, immune dysfunction, coagulopathy and mitochondrial dysfunction. New drugs are required to prevent inflammatory hyperdrive and support a VA-coupled, high flow, vasodilatory system with endothelial-glycocalyx protection and tissue oxygenation (185). HR, heart rate; ATP, adenosine triphosphate; CNS, central nervous system; NTS, nucleus tractus solitarius; PVN, paraventricular nucleus of the hypothalamus; MAP, mean arterial pressure. PIICS, Persistent Inflammation, Immunosuppression and Catabolism Syndrome, see text for description of early and late deaths.