β2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

Abstract
We previously showed that β2-microglobulin knockout mice treated with anti-asialoGM1 (β2M/αAsGM1 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 β2M/αAsGM1 mice after CLP. However, β2M/αAsGM1 mice exhibited improved mean arterial pressure and systemic vascular resistance compared with wild-type mice. Myocardial function was also better preserved in β2M/αAsGM1 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, β2M/αAsGM1 mice exhibit improved hemodynamics and cardiac contractile function after CLP that may account, in part, for our previously observed survival benefit.