Background: The aims of the present study were to establish a clinically relevant two-hit model with trauma/hemorrhage followed by sepsis in older mice and investigate age-dependent cardiovascular and immunologic specificities under these conditions.
Materials and methods: In aged mice (12, 18, and 24 mo old), a femur fracture followed by hemorrhage was induced. After resuscitation, animals were monitored for 72 h before sepsis was induced. Vital signs were monitored during shock. Systemic interleukin (IL)-6 levels were measured daily. Expression of sarcoplasmic or endoplasmic reticulum calcium ATPase (SERCA) and IL-6 receptor were analyzed in heart, lung, and liver tissues.
Results: After induction of shock, mean arterial pressure decreased significantly in all groups (12 mo, P < 0.001; 18 mo, P < 0.001; 24 mo, P = 0.013). Compared with younger animals, 24-mo old mice were not able to adequately compensate for hypovolemia by an increase of heart rate (P = 0.711). Expression of SERCA2 (P = 0.002) and IL-6 receptor on myocytes (P = 0.037), lung (P = 0.005), and liver (P = 0.009) tissues were also lowest in this group. Systemic IL-6 values showed the most distinct posttraumatic response in 24-mo-old mice (P = 0.016). Survival rate decreased significantly with increased age (P = 0.005).
Conclusions: The increased mortality rate in older animals was associated with a limited compensatory physiological response and a more distinct immunologic reaction after trauma and sepsis. A decreased SERCA2 expression and missing feedback loops due to a reduced density of organ bound immune receptors might represent possible explanations for the observed age-dependent differences.
Keywords: Elderly; Geriatric; IL-6R; IL6; Immune response; Multiple trauma; Old; Physiological response; Polytrauma; SERCA2.
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