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Non-Human Primate (Rhesus Macaque) Models of Severe Pressure-Targeted Hemorrhagic and Poly-Traumatic Hemorrhagic Shock.

Shock 2017 June 14
BACKGROUND: We endeavored to develop clinically translatable non-human primate (NHP) models of severe poly-traumatic hemorrhagic shock.

METHODS: NHPs were randomized into five pressure-targeted severe hemorrhagic shock (PTHS) ± additional injuries scenarios: 30-min PTHS (PTHS-30), 60-min PTHS (PTHS-60), PTHS-60 + soft tissue injury (PTHS-60+ST), PTHS-60+ST + femur fracture (PTHS-60+ST+FF) and decompensated PTHS+ST+FF (PTHS-D). Physiologic parameters were recorded and blood samples collected at five time points with animal observation through T = 24hrs. Results presented as mean ± SEM; statistics: log transformation followed by two-way ANOVA with Bonferroni multiple comparisons, Wilcoxon non-parametric test for comparisons and the Friedmans's one-way ANOVA; significance: p < 0.05.

RESULTS: Percent blood loss was 40% ± 2, 59% ± 3, 52% ± 3, 49% ± 2, and 54% ± 2 for PTHS-30, PTHS-60, PTHS-60+ST, PTHS-60+ST+FF, and PTHS-D, respectively. All animals survived to T = 24hrs except one in each of the PTHS-60 and PTHS-60+ST+FF groups and seven in the PTHS-D group. Physiologic, coagulation, and inflammatory parameters demonstrated increasing derangements with increasing model severity.

CONCLUSION: NHPs exhibit a high degree of resilience to hemorrhagic shock and poly-trauma as evidenced by moderate perturbations in metabolic, coagulation, and immunologic outcomes with up to 60 minutes of profound hypotension regardless of injury pattern. Extending the duration of PTHS to the point of decompensation in combination with poly-traumatic injury, evoked derangements consistent with those observed in severely injured trauma patients which would require ICU care. Thus, we have successfully established a clinically translatable NHP trauma model for use in testing therapeutic interventions to trauma.

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