N. G. Vigneshwar1, E. E. Moore2, G. R. Stettler1, G. R. Nunns1, M. Fragoso2, J. M. Samuels1, M. G. Bartley1, J. R. Coleman1, A. Sauaia1, A. Banerjee1, C. C. Silliman3 1University Of Colorado Denver,Surgery,Aurora, CO, USA 2Denver Health Medical Center,Surgery,Denver, CO, USA 3Children’s Hospital Colorado,Hematology,Aurora, CO, USA
Introduction: Hyperfibrinolysis, driven by tissue plasminogen activator (tPA) and associated with shock, is a major contributor to trauma-induced coagulopathy. The mechanism by which shock stimulates tPA release is unknown. Shock leads to both decreased flow and O2 carrying capacity to a tissue bed. We hypothesize that maintained flow rates to the liver do not induce early release of tPA in a model of systemic hypoxemia.
Methods: There were four groups of male rats: control (n=4), shock (n=6), 50% plasma replacement (PR) (n=5), and 75% PR (n=2) to simulate a model of decreased oxygen carrying capacity with maintained flow. Rats underwent femoral artery and vein cannulation and mini laparotomy for liver access. An OxyProbe device placed over the liver evaluated blood flow changes. Shock animals were bled to maintain a mean arterial pressure (MAP) of <30mmHg. PR was accomplished by infusing an equivalent volume of banked rat plasma to the blood volume removed. ABGs were obtained at 0, 5, 15, and 30 minutes. Platelet-free plasma (0, 15 and 30 minutes) was used to measure total tPA concentrations.
Results: MAP was maintained in PR groups compared to control at all time points (P>0.05). Compared to control, shock had a lower MAP at all time points (P<0.02). At t=15 both PR groups and shock had lower O2 content vs. control (control: 18.67±1.17, 50% PR: 8.98±1.20, 75% PR: 6.37±0.18, Shock: 13.04±3.29 ml/dL P<0.006). Compared to shock both PR groups had lower O2 content (P<0.05). At t=30, both PR groups and shock had lower O2 content vs. control (control: 16.7±2.1, 50% PR: 7.8±0.28, 75% PR: 5.55±0.24, Shock 3.87±5.62 ml/dL P<0.001). Compared to shock, both PR groups did not have significantly different arterial O2 content (P>0.5). At t=15min, flows, measured by fold-change vs. baseline, were: control -8.50±18.4, shock: -54.7 ±6.55, 50% PR: 27.45±19.8 and 75% PR: 12.93±0.634 (P<0.05). At t=30, control: -5.329±22.4, shock: -74.42±8.49, 50% PR: 15.6±15.9, 75% PR: 21.1±3.03 (P<.05). At t=15 and t=30, shock had lower flow versus control (P.024 and P<.001, respectively). PR groups and control had similar flows at all time points (P>.05). At t=30, tPA release, measured by fold-change vs. baseline, were as follows: control: -0.077±0.195, shock: 3.31±1.51, 50% PR: -0.053±0.998 and 75% PR: 0.03±0.543 (P<0.05). Compared to control, shock showed a trend toward increased release of tPA at 30 min (p=0.06), and PR groups had a similar increase in TPA release (P>0.9) (Figure 1).
Conclusion: Low flow but not hypoxemia alone contributes to tPA release. The low blood flow state is, at least partially, responsible for systemic hyperfibrinolysis following injury while isolated hypoxemia is not a stimulus for tPA release.
