Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography

A small animal model of sepsis that reproduces the vasodilation, hypotensio n, increased cardiac output, and response to treatment seen in patients wit h septic shock would be useful for studies of pathophysiology and treatment , but no current models replicate all of these features. Mice were made sep tic by cecal ligation and puncture and resuscitated with fluids and antibio tics every 6 h. Blood pressure was measured in anesthetized mice with manom etric catheters, and echocardiography was performed in these animals every 6 h. Survival in treated septic mice was improved compared with untreated m ice (44% versus 0%, p < 0.01). In control mice, heart rate (HR, 420 +/- 31 beats/min), mean arterial pressure ((Pa) over bar, 100 +/- 8 mm Hg), stroke volume (SV, 26 +/- 4 mul), and cardiac output (12.5 +/- 6.6 ml/min) were u nchanged over 48 h. In septic mice (Pa) over bar was significantly decrease d (102 +/- 14 to 65 +/- 19 mm Hg, p < 0.02), starting at 12 h. HR and cardi ac 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 mul) remained constant. This fluid-resuscitated, antibiotic-treated model replicates the mortality, hypotension, and hyperdynamic state seen in clin ical sepsis. Precise determination of serial hemodynamics in this model may be useful to elucidate pathophysiologic mechanisms and to evaluate new the rapies for septic shock.