Characterization of a Hyperdynamic Murine Model of Resuscitated Sepsis Using Echocardiography

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Abstract
A small animal model of sepsis that reproduces the vasodilation, hypotension, increased cardiac output, and response to treatment seen in patients with septic shock would be useful for studies of pathophysiology and treatment, but no current models replicate all of these features. Mice were made septic by cecal ligation and puncture and resuscitated with fluids and antibiotics every 6 h. Blood pressure was measured in anesthetized mice with manometric catheters, and echocardiography was performed in these animals every 6 h. Survival in treated septic mice was improved compared with untreated mice (44% versus 0%, p < 0.01). In control mice, heart rate (HR, 420 +/- 31 beats/min), mean arterial pressure (Pa, 100 +/- 8 mm Hg), stroke volume (SV, 26 +/- 4 microl), and cardiac output (12.5 +/- 6.6 ml/min) were unchanged over 48 h. In septic mice Pa was significantly decreased (102 +/- 14 to 65 +/- 19 mm Hg, p < 0.02), starting at 12 h. HR and cardiac output increased significantly (HR, 407 +/- 70 to 524 +/- 76 beats/min, cardiac output, 11.6 +/- 2.0 to 17.1 +/- 1.5 ml/min, p < 0.01). SV (24 +/- 5 microl) remained constant. This fluid-resuscitated, antibiotic-treated model replicates the mortality, hypotension, and hyperdynamic state seen in clinical sepsis. Precise determination of serial hemodynamics in this model may be useful to elucidate pathophysiologic mechanisms and to evaluate new therapies for septic shock.