Abstract P120: Effect of Age on Hemodynamics, Heart Rate Variability, and Outcome in a Murine Model of Sepsis

Abstract

Background: The incidence and mortality of sepsis increase with aging, but animal models often use young animals whose biological ages do not reflect patient populations. We compared old and young mice in a murine model of resuscitated sepsis. Methods: C57Bl/6 mice (Young 2–3 months, n=32; Old 15–20 months, n=24) were made septic by cecal ligation and puncture (CLP) and resuscitated with fluids and antibiotics q 6 hr; controls underwent sham ligation. Serial echocardiography using a 30MHz probe was performed under light isoflurane anesthesia for measurement of stroke volume (SV), fractional shortening (FS), and cardiac output (CO). Blood pressure was measured using implantable radiotelemeters. From the waveforms, heart rate volatility (% of 5 minute intervals with standard deviation < the lowest 5% of baseline), an index of heart rate variability less susceptible to artifact than other measures, was derived for the entire experiment. Results: After CLP, heart rate and blood pressure did not differ significantly between old and young mice. SV decreased early in both groups (old 54.4 to 25.6 μL, young 57.2 to 24.0 p<0.01 vs baseline), as did CO. With resuscitation, SV and CO improved in both groups (old 48.0 μL and 24.5 ml/min, young 44.0 μL and 20.7 ml/min). Old animals were larger than young animals, but normalized values (% change from baseline) for SV, CO, and LVEDV were similar after CLP. Old septic mice had more periods of low heart rate volatility than young septic mice or old controls (62% vs 37% vs 3% of the experimental period). Mortality tended to be higher in old than young mice (46% vs 22% at 72 hr, p=0.09, 54% vs 22% at 144 hr, p=0.06). Conclusion: In a clinically relevant model of murine sepsis, age did not have a significant impact on hemodynamics, but decreased heart rate variability was more prominent in aged mice, and age was associated with increased mortality. This suggests the potential for nonlinear hemodynamic parameters to provide insights into both the pathogenesis of disease and the effects of aging.