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Updated: Aug 8, 2026
Cecal Ligation Puncture Procedure
Published on: May 7, 2011
Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in CD8 knockout mice treated with
Weike Tao1, Victor T Enoh, Cheng Y Lin
1Dept. of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555-0591, USA.
Abstract:
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/alphaAsGM1 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/alphaAsGM1 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/alphaAsGM1, mice compared with sham controls. Myocardial function was better preserved in CD8KO/alphaAsGM1 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/alphaAsGM1 mice. These observations likely explain, in part, the previously observed survival advantage of CD8KO/alphaAsGM1 mice following CLP.
Insights
CD8-knockout mice treated with anti-asialoGM1 (CD8KO/alphaAsGM1) show improved hemodynamics and preserved myocardial function following sepsis-induced injury (CLP). This attenuation of cardiovascular collapse and shock contributes to their increased survival.
Area of Science:
- Immunology
- Cardiovascular Physiology
- Sepsis Pathophysiology
Background:
- Sepsis, often induced by cecal ligation and puncture (CLP), leads to significant cardiovascular dysfunction and organ injury.
- The role of CD8+ T-cells in sepsis-induced myocardial depression and hemodynamic instability remains incompletely understood.
Purpose of the Study:
- To evaluate the impact of depleting CD8+ T-cells using anti-asialoGM1 on hemodynamics and myocardial function in a murine sepsis model at 18 hours post-injury.
- To investigate the association between myocardial inflammation and cardiac dysfunction in wild-type versus CD8-depleted mice after CLP.
Main Methods:
- Cecal ligation and puncture (CLP) model in CD8-knockout mice treated with anti-asialoGM1 (CD8KO/alphaAsGM1) and compared to wild-type mice.
- Hemodynamic assessment including mean arterial pressure and systemic vascular resistance via carotid artery cannulation.
- Left ventricular pressure-volume analysis using a conductance catheter to evaluate myocardial contractility and function.
- Measurement of blood acid-base balance and serum creatinine to assess organ injury.
Main Results:
- CD8KO/alphaAsGM1 mice demonstrated higher mean arterial pressure and increased systemic vascular resistance compared to wild-type mice post-CLP.
- Cardiac output was preserved in CD8KO/alphaAsGM1 mice, whereas wild-type mice exhibited a significant decrease compared to sham controls.
- Myocardial function, assessed by left ventricular pressure development and elastance, was significantly better preserved in CD8KO/alphaAsGM1 mice.
- Wild-type mice showed impaired myocardial function linked to proinflammatory cytokine mRNA induction in the heart, along with metabolic acidosis and elevated creatinine.
Conclusions:
- Depletion of CD8+ T-cells attenuates sepsis-induced cardiovascular collapse, characterized by hypotension, myocardial depression, and low systemic vascular resistance.
- The preserved cardiac function and hemodynamic stability in CD8KO/alphaAsGM1 mice contribute to their improved survival following CLP.
- These findings highlight the critical role of CD8+ T-cells in the pathogenesis of sepsis-induced cardiac dysfunction.
