Abstract 139: Endothelial Nitric Oxide Synthase Inhibition Causes Alterations in Nonlinear Hemodynamic Parameters in a Murine Model of Sepsis
Background Nitric oxide may play a role in the altered hemodynamics seen in sepsis, but the mechanisms involved have not been fully understood. To better understand this mechanism, we compared standard and non-linear hemodynamics during sepsis in mice with a deficiency of endothelial nitric oxide synthase (eNOS).
Hypothesis Inhibition of eNOS will cause changes in non-linear hemodynamic parameters different from changes seen in wild type animals in a murine model of sepsis.
Methods Radio-transmitters were implanted into the aorta of C57/BL6 wild type (n=15) and C57/BL6 NOS 3 (eNOS knockout) (n=7) mice for continuous hemodynamic monitoring. After 72 hours of recovery, baseline heart rate recordings were captured for 24 hours. Sepsis was induced by cecal ligation and puncture and continuous recordings were taken for 48 hours. All mice received antibiotics (ceftriaxone and clindamycin) and fluids (35mg/kg 0.9% NaCl) every 6 hours. Volatility was used as a measurement of variability. Heart rate volatility (HRV) and blood pressure volatility (BPV) measurements were compared between groups.
Results At baseline the eNOS knockout mice had higher mean systolic blood pressure (156 vs. 126 mmHg, p<0.001) and lower mean heart rate (464 vs. 534, p<0.001) compared to wild type mice. Following induction of sepsis, heart rate and blood pressure were similar between the two groups. During sepsis the eNOS knockout mice had fewer normal intervals of both HRV (24.1 vs. 33.3%, p<0.001) and BPV (38.1 vs. 62.8%, p<0.001) compared to the wild type mice. There was no difference in survival between the two groups (28.6% vs. 26.7%, p=1.0).
Conclusions During sepsis eNOS knockout mice demonstrated a greater drop in blood pressure from baseline compared to wild-type mice, and showed worsening of non-linear hemodynamic parameters. Inhibition of eNOS did not lead to improved survival during sepsis. In conclusion, eNOS inhibition worsens both heart rate and blood pressure variability during sepsis.
- © 2011 by American Heart Association, Inc.