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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in CD8 knockout mice treated with anti-asialoGM1

Departments of ¹Anesthesiology and ²Microbiology and Immunology, The University of Texas Medical Branch and ³The Shriners Hospital for Children, Galveston; ⁴Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center, Dallas, Texas

Submitted 4 February 2005 ; accepted in final form 20 April 2005

The present study was designed to assess hemodynamics and myocardial function at 18 h after injury caused by cecal ligation and puncture (CLP) in CD8-knockout mice treated with anti-asialoGM1 (CD8KO/AsGM1 mice). Arterial pressure was measured by carotid artery cannulation, and left ventricular pressure-volume measurements were obtained by use of a 1.4-Fr conductance catheter. Blood acid-base balance and indexes of hepatic, renal, and pulmonary injury were also measured. CD8KO/AsGM1 mice exhibited higher mean arterial pressure and increased systemic vascular resistance compared with wild-type mice. Cardiac output was significantly decreased in wild-type, but not CD8KO/AsGM1, mice compared with sham controls. Myocardial function was better preserved in CD8KO/AsGM1 mice as indicated by less impairment of left ventricular pressure development over time, time varying maximum elastance, end-systolic pressure-volume relationship, and preload recruitable stroke work. The impairment in myocardial function was associated with induction of proinflammatory cytokine mRNAs in the hearts of wild-type mice. The hemodynamic derangements in wild-type mice were coupled with significant metabolic acidosis and elevated serum creatinine levels. Overall, this study shows that cardiovascular collapse and shock characterized by hypotension, myocardial depression, low systemic vascular resistance, and metabolic acidosis occurs after CLP in wild-type mice but is attenuated in CD8KO/AsGM1 mice. These observations likely explain, in part, the previously observed survival advantage of CD8KO/AsGM1 mice following CLP.

blood pressure; vascular resistance; cardiac output; left ventricular function; perfusion

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