Abstract 47: Left Ventricular Dilation Determines Outcome in Septic Mice
Introduction: Myocardial dysfunction with decreased ejection fraction is an important component of the hemodynamic abnormalities seen with sepsis and septic shock. Preservation of stroke volume (SV) by LV dilation has been associated with improved survival in humans. We studied the incidence, mechanism, and impact on survival of LV dilation in a clinically relevant model of murine sepsis.
Methods: 23 C57Bl/6 (WT) and 4 eNOS-deficient mice (eNOSKO) were made septic by cecal ligation and puncture (CLP). After CLP animals received fluids (35 mL/kg saline) and antibiotics (ceftriaxone 30mg/kg and clindamycin 25mg/kg) q6hr. Animals were anesthetized briefly with isoflurane and cardiac performance was assessed every 3 hrs for 36 hr, then every 12hr with echocardiography using a 30Mhz probe. Stroke Volume (SV, μL) was assessed by Doppler, Fractional Shortening (FS, %) by short axis M-mode, and Cardiac Output (CO, mL/min) was calculated as SV*HR. LV dilation was defined as an increase in LV diameter > 5% by short-axis M-mode.
Results: In WT, 8 mice (35%) demonstrated LV dilation (D), while 15 (64%) did not (ND). None of the eNOSKO mice dilated, and none survived. FS was lower in dilators than non-dilators (27 ± 5 vs 33 ± 4), but the ability to maintain stroke volume was associated with LV dilation. With resuscitation both D and ND improved SV and CO, but only D animals achieved a normodynamic state at 24 hr. Overall survival was 52%. All animals with dilation lived, and survival was significantly better than in non-dilators (100% vs 32%, p < 0.01).
Conclusions: In a clinically relevant murine model of sepsis, the LV dilation phenotype was associated with improved survival. Failure of eNOSKO mice to dilate suggests that effects of NO in this model may be isoform-specific, and that lusitropic effects of NO in sepsis may have a more important impact on clinical outcome than inotropic effects.