(627.8) Effects of extremity trauma on physiological responses and survival to hemorrhage in conscious rats

Poster Board Number: E687

Carmen Hinojosa-Laborde (US Army Institute of Surgical Research), Mariam Calderon (US Army Institute of Surgical Research), Cassandra Rodriguez (US Army Institute of Surgical Research), Brian Connor (US Army Institute of Surgical Research), Kathy Ryan (US Army Institute of Surgical Research), Harold Klemcke (US Army Institute of Surgical Research)

Background: Under most circumstances of battlefield injuries, trauma accompanies hemorrhage.  Interestingly, there are few experimental animal models of trauma and hemorrhage. The compensatory cardiovascular responses during hemorrhage are well documented, and serve to maintain adequate perfusion of vital organs during conditions of loss of blood volume.  While trauma alone has been shown to increase heart rate (HR) and vascular resistance, the effects of trauma on compensatory cardiovascular responses and the ability to survive hemorrhage have not been clearly defined.  The purpose of this study is to determine the effects of an extremity injury that combines hard (bone) and soft (skeletal muscle) tissue trauma, on blood pressure (BP) and HR responses, and survival to hemorrhage in conscious rats.  We hypothesized that trauma would impair compensatory cardiovascular responses, and decrease survival after hemorrhage.

Methods: All rats (male; ~ 350grams) were surgically implanted with a telemetry transmitter for measurement of BP and HR, and allowed to recover for 2 weeks prior to the experiment.  A carotid catheter was inserted one day before the experiment. There were two experimental groups: hemorrhage with no trauma (n=20); and hemorrhage with trauma (n=20). On the day of experiment, rats were anesthetized briefly (10 min) to undergo trauma (crushing of the right gastrocnemius and semimembranosus muscles for 30 sec with forceps) and fibula fracture. No trauma groups were only anesthetized for 10 min without manipulation of the extremity.  Rats were allowed to awaken, and 90 min later the rats underwent a conscious hemorrhage (~50% of blood volume during 25 min) via the indwelling carotid catheter. BP and HR measures were collected over 1 min intervals for 240 minutes after hemorrhage and analyzed via Data Sciences International software. Survival time and survival ratio to 240 minutes were determined. Data were analyzed via multi-way analysis of variance for repeated measures and Kaplan-Meier procedure using the Statistical Analysis System. Data are shown as mean ± standard deviation.

Results:   Compared with no trauma, trauma increased HR during hemorrhage (P = 0.03), but had no effect on BP (P = 0.88). After hemorrhage completion, trauma decreased BP for approximately one hour (P = 0.032), but only transiently decreased HR.  After hemorrhage, survival time (Trauma: 156.8 ± 80.7 and No Trauma: 210.6 ± 61.8 min, p = 0.022), and survival ratio (Trauma: 9/20 and No Trauma: 16/20, p=0.048), were significantly lower in animals with trauma compared to no trauma.

Conclusions: Our results show that the presence of trauma affects compensatory mechanisms to maintain BP, and negatively impacts the ability to survive hemorrhage.  These findings indicate the importance of including both trauma and hemorrhage in the development of animal models to study treatments for hemorrhage in wounded Soldiers on the battlefield or civilian trauma victims.

Applied Pain Research Program, US Army Clinical and Rehabilitative Medicine/Joint Program Committee 8, and US Army Combat Casualty Care Research Program, US Army Medical Research and Development Command