Nonhuman Primate (Rhesus Macaque) Models of Severe Pressure-Targeted Hemorrhagic and Polytraumatic Hemorrhagic Shock.

BACKGROUND: We endeavored to develop clinically translatable nonhuman primate (NHP) models of severe polytraumatic hemorrhagic shock. METHODS: NHPs were randomized into five severe pressure-targeted hemorrhagic shock (PTHS) ±â€Šadditional 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 = 24 h. Results presented as mean ±â€ŠSEM; statistics: log transformation followed by two-way ANOVA with Bonferroni multiple comparisons, Wilcoxon nonparametric test for comparisons, and the Friedmans' one-way ANOVA; significance: P < 0.05. RESULTS: Percent blood loss was 40% ±â€Š2, 59% ±â€Š3, 52% ±â€Š3, 49% ±â€Š2, and 54% ±â€Š2 for PTHS-30, PTHS-60, PTHS-60+ST, PTHS-60+ST+FF, and PTHS-D, respectively. All animals survived to T = 24 h 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 polytrauma as evidenced by moderate perturbations in metabolic, coagulation, and immunologic outcomes with up to 60 min of profound hypotension regardless of injury pattern. Extending the duration of PTHS to the point of decompensation in combination with polytraumatic 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.

Differences in postsurgical recovery of CF1 mice after intraperitoneal implantation of radiotelemetry devices through a midline or flank surgical approach.

Minimizing the pain or discomfort of research animals through refinement of surgical techniques is inherent in the humane use of animals in investigative studies. The current approach for intraperitoneal implantation of radiotelemetry devices in mice is a ventral midline incision. An optional surgical approach is a flank incision. We used multidimensional analysis to compare midline and flank approaches for implantation of radiotelemetry devices in regard to time of surgery, activity, temperature, food intake, gel intake, body weight, and vitality scores. A third group was used to evaluate the effects of buprenorphine in healthy mice. The study demonstrated positive benefits related to the flank approach, including quicker surgery times, improved activity levels, more stable temperature homeostasis, smaller losses in body weight, and quicker return to presurgical baseline levels of food intake. In addition, direct effects of buprenorphine included decreases in food intake and body weight, with the effects on body weight lasting approximately 8 d after treatment. Collectively, these results suggest that implantation of intraperitoneal radiotelemetry devices by using a flank approach is beneficial to mice.

Comparison of buprenorphine and butorphanol analgesia in the eastern red-spotted newt (Notophthalmus viridescens).

The experimental use of amphibian models in biomedical research increases yearly, but there is a paucity of reports concerning analgesic use in many of these species. In this study, buprenorphine given by intracoelomic injection and butorphanol added to the tank water were compared for analgesic effect in the eastern red-spotted newt after bilateral forelimb amputations. Newts undergoing anesthesia but not surgery and newts having surgery but not given analgesia postoperatively were used as control groups. Animals were tested for food consumption, spontaneous movement, response to tapping on the tank, response to being touched, and body posture. Both buprenorphine by intracoelomic injection and butorphanol in tank water significantly promoted resumption of normal behavior after bilateral surgical amputation of the forelimbs. The difference between analgesic treatment and no analgesic treatment was maintained until 72 h after surgery.

Telemetric analysis to detect febrile responses in mice following vaccination with a live-attenuated virus vaccine.

Non-human primates (NHP) are considered to be the most appropriate model for predicting how humans will respond to many infectious diseases. Due to ethical and monetary concerns associated with the use of NHP, rodent models that are as predictive of responses likely to be seen in human vaccine recipients are warranted. Using implanted telemetry devices, body temperature and activity were monitored in inbred and outbred mouse strains following administration of the live-attenuated vaccine for Venezuelan equine encephalitis virus (VEEV), V3526. Following analysis of individual mouse data, only outbred mouse strains showed changes in diurnal temperature and activity profiles following vaccination. Similar changes were observed following VEEV challenge of vaccinated outbred mice. From these studies, we conclude, outbred mouse strains implanted with telemeters are a sensitive model for predicting responses in humans following vaccination.

From the combat medic to the forward surgical team: the Madigan model for improving trauma readiness of brigade combat teams fighting the Global War on Terror.

BACKGROUND: Medics assigned to combat units have a notable paucity of trauma experience. Our goal was to provide intense trauma refresher training for the conventional combat medic to better prepare them for combat casualty care in the War on Terror. MATERIALS AND METHODS: Our Tactical Combat Casualty Care Course (TC3) consisted of the following five phases: (1) One and one-half-day didactic session; (2) Half-day simulation portion with interactive human surgical simulators for anatomical correlation of procedures and team building; (3) Half-day of case presentations and triage scenarios from Iraq/Afghanistan and associated skills stations; (4) Half-day live tissue lab where procedures were performed on live anesthetized animals in a controlled environment; and (5) One-day field phase where live anesthetized animals and surgical simulators were combined in a real-time, field-training event to simulate realistic combat injuries, evacuation problems, and mass casualty scenarios. Data collection consisted of surveys, pre- and posttests, and after-action comments. RESULTS: A total of 1317 personnel participated in TC3 from October 2003 through May 2005. Over the overlapping study period from December 2004 to April 2005, 327 soldiers participated in the formal five-phase course. Three hundred four (94%) students were combat medics who were preparing for combat operations in Iraq or Afghanistan. Of those completing the training, 97% indicated their confidence and ability to treat combat casualties were markedly improved. Moreover, of those 140 medics who took the course and deployed to Iraq for 1 year, 99% indicated that the principles taught in the TC3 course helped with battlefield management of injured casualties during their deployment. CONCLUSION: The hybrid training model is an effective method for training medical personnel to deal with modern battle injuries. This course increases the knowledge and confidence of combat medics deploying and fighting the Global War on Terrorism.