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REGULATION IN GENETICALLY MODIFIED ANIMALS

2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

¹Department of Anesthesiology, The University of Texas Medical Branch and the ²Shriners Hospital for Children, Galveston, Texas 77555-0591

Submitted 19 August 2003 ; accepted in final form 17 November 2003

We previously showed that 2-microglobulin knockout mice treated with anti-asialoGM1 (2M/AsGM1 mice) exhibit less hypothermia, reduced production of proinflammatory cytokines, less metabolic acidosis, and improved survival after cecal ligation and puncture (CLP) compared with wild-type mice. The present study was designed to assess hemodynamics and left ventricular contractility at 18 h after CLP. Arterial pressure was measured by carotid artery cannulation, and left ventricular pressure-volume loops were obtained by insertion of a 1.4-F conductance catheter into the left ventricle. Heart rate, stroke volume, and cardiac output were not significantly different between wild-type and 2M/AsGM1 mice after CLP. However, 2M/AsGM1 mice exhibited improved mean arterial pressure and systemic vascular resistance compared with wild-type mice. Myocardial function was also better preserved in 2M/AsGM1 mice as indicated by improved left ventricular pressure development over time, time-varying maximum elastance, endsystolic pressure-volume relationship, and preload recruitable stroke work. Overall, this study shows that cardiovascular collapse characterized by hypotension, myocardial depression, and low systemic vascular resistance occurs after CLP in wild-type mice. However, 2M/AsGM1 mice exhibit improved hemodynamics and cardiac contractile function after CLP that may account, in part, for our previously observed survival benefit.

cecal ligation and puncture; blood pressure; vascular resistance; cardiac output; pressure-volume relationships

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