An HDL‐mimetic peptide improves cardiac performance and lipoprotein profiles in septic rodents

Abstract

Background: Cardiac failure is a common cause of death in septic patients, and elevating plasma HDL reduces sepsis complications.Objective: We tested the hypothesis that the apoA‐I mimetic peptide L‐4F improves cardiac function in rats undergoing cecal ligation and puncture (CLP).Methods: Male Sprague‐Dawley rats were randomized to undergo CLP or sham surgery. CLP rats were further subdivided to receive saline (n=11) or L‐4F (10mg/kg, n=12) by ip. injection 6 hours after sepsis induction. Sham‐operated rats received saline (n=8).Results: There was a significant decrease in right atrial pressure, left ventricular end‐diastolic volume, stroke volume and cardiac output 24hrs after CLP. L‐4F blunted changes in these parameters in CLP rats and improved ejection fraction. Lipoprotein profiles were altered by CLP surgery after 24 hrs. Total cholesterol (TC) was reduced from 96± 4 to 51± 4 mg/dl in CLP rats and was principally characterized by a reduction in HDL (80± 3 to 23± 3). L4F administration to CLP rats attenuated this shift in lipoproteins (TC: 67± 5/HDL: 43± 3).Conclusion: L‐4F treatment improved cardiac performance in CLP rats compared to saline‐treated controls. This was associated with an increase in HDL cholesterol and a decrease in plasma and cardiac cytokines. It is hypothesized that HDL reduces sepsis complications by neutralizing pathogens, such as endotoxin, in CLP rats. Supported by NIH DK070040.