TY - JOUR
T1 - Development, refinement, and characterization of a nonhuman primate critical care environment
AU - Bozzay, Joseph D.
AU - Walker, Patrick F.
AU - Atwood, Rex E.
AU - DeSpain, Robert W.
AU - Parker, William J.
AU - Chertow, Daniel S.
AU - Mares, John A.
AU - Leonhardt, Crystal L.
AU - Elster, Eric A.
AU - Bradley, Matthew J.
N1 - Publisher Copyright:
© 2023 Public Library of Science. All rights reserved.
PY - 2023/3
Y1 - 2023/3
N2 - Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers. Methods Eight adult male rhesus macaques underwent ventilation with sedation for 48 96 hours in a critical care setting. Three of these NHPs underwent "sham" procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/ chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy. Results Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72 96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed. Conclusions A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-Term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model.
AB - Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers. Methods Eight adult male rhesus macaques underwent ventilation with sedation for 48 96 hours in a critical care setting. Three of these NHPs underwent "sham" procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/ chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy. Results Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72 96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed. Conclusions A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-Term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model.
UR - http://www.scopus.com/inward/record.url?scp=85150228451&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0281548
DO - 10.1371/journal.pone.0281548
M3 - Article
C2 - 36930612
AN - SCOPUS:85150228451
SN - 1932-6203
VL - 18
JO - PLoS ONE
JF - PLoS ONE
IS - 3 March
M1 - e0281548
ER -