Key result
Administration of the apolipoprotein A-I mimetic peptide 4F significantly reduced 48-hour mortality from 71% to 43% in rats subjected to polymicrobial sepsis.
Why the study?
Does the apolipoprotein A-I mimetic peptide 4F improve survival, cardiac function, and inflammatory responses in a rat model of sepsis?
Does the apolipoprotein A-I mimetic peptide 4F improve survival, cardiac function, and inflammatory responses in a rat model of sepsis?
In a rat model of sepsis, treatment with the apoA-I mimetic peptide 4F attenuated the reduction in plasma HDL, improved cardiac output, and reduced mortality.
Answers are grounded in this paper and cite their sources.
May support apoA-I mimetic development for sepsis; leaves open translation from rodent models to clinical trials.
Systemic inflammation induces a multiple organ dysfunction syndrome that contributes to morbidity and mortality in septic patients. Since increasing plasma apolipoprotein A-I (apoA-I) and HDL may reduce the complications of sepsis, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in rats undergoing cecal ligation and puncture (CLP) injury. Male Sprague-Dawley rats were randomized to undergo CLP or sham surgery. IL-6 levels were significantly elevated in plasma by 6 h after CLP surgery compared with shams. In subsequent studies, CLP rats were further subdivided to receive vehicle or 4F (10 mg/kg) by intraperitoneal injection, 6 h after sepsis induction. Sham-operated rats received saline. Echocardiographic studies showed a reduction in left ventricular end-diastolic volume, stroke volume, and cardiac output (CO) 24 h after CLP surgery. These changes were associated with reduced blood volume and left ventricular filling pressure. 4F treatment improved blood volume status, increased CO, and reduced plasma IL-6 in CLP rats. Total cholesterol (TC) and HDL were 79 +/- 5 and 61 +/- 4 mg/dl, respectively, in sham rats. TC was significantly reduced in CLP rats (54 +/- 3 mg/dl) due to a reduction in HDL (26 +/- 3 mg/dl). 4F administration to CLP rats attenuated the reduction in TC (69 +/- 4 mg/dl) and HDL (41 +/- 3 mg/dl) and prevented sepsis-induced changes in HDL protein composition. Increased plasma HDL in 4F-treated CLP rats was associated with an improvement in CO and reduced mortality. It is proposed that protective effects of 4F are related to its ability to prevent the sepsis-induced reduction in plasma HDL.
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Zhang et al. (2009) studied Sepsis. Apolipoprotein A-I mimetic peptide 4F vs. Saline vehicle was evaluated on Mortality at 48 hours (p=<0.05). Administration of the apolipoprotein A-I mimetic peptide 4F significantly reduced 48-hour mortality from 71% to 43% in rats subjected to polymicrobial sepsis.
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