Beta2-microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis.
We previously showed that beta2-microglobulin knockout mice treated with anti-asialoGM1 (beta2M/alphaAsGM1 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 beta2M/alphaAsGM1 mice after CLP. However, beta2M/alphaAsGM1 mice exhibited improved mean arterial pressure and systemic vascular resistance compared with wild-type mice. Myocardial function was also better preserved in beta2M/alphaAsGM1 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, beta2M/alphaAsGM1 mice exhibit improved hemodynamics and cardiac contractile function after CLP that may account, in part, for our previously observed survival benefit.
Tao
Weike
W
Department of Anesthesiology, The University of Texas Medical Branch, Galveston, Texas 77555-0591, USA.
Sherwood
Edward R
ER
D000005:Abdomen; D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005260:Female; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D007022:Hypotension / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000235:genetics* / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology*; D014655:Vascular Resistance / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology*
D001613:beta 2-Microglobulin; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside