Evidence map›Paper›PMID 40999545›Full record

Observational studyCritical care (London, England)2025

Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness.

Anna Kleyman, Walter Pisciotta, Charlotte Gaupp, Waqas Khaliq, Daniel Hofmaenner, David Brealey, Bernardo Bollen Pinto, Davide Tommaso Andreis, Mark Gerard Waugh, Miranda J Melis and 5 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Critical care (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Anna KleymanBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Walter PisciottaBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Charlotte GauppBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Waqas KhaliqBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Daniel HofmaennerBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
David BrealeyBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Bernardo Bollen PintoBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Davide Tommaso AndreisBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Mark Gerard WaughDivision of Medicine, University College London, London, UK.
Miranda J MelisBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Muska MillerBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
Klea MehmetajDept of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
Michael BauerDept of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
Adrian PressDept of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
Mervyn SingerBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK. m.singer@ucl.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSepsis-induced cardiomyopathy (SIM) is characterized by myocardial dysfunction, diminished catecholamine responsiveness and worse outcomes. Hypocholesterolemia is also a well-recognized prognosticator of poor outcomes in sepsis. In vitro physiology/pharmacology studies indicate that low cholesterol levels within the cardiomyocyte membrane regulate ß-adrenergic receptor activity. We therefore hypothesized that cardiomyocyte membrane cholesterol levels are reduced in sepsis and this contributes to SIM.

methodsCardiovascular biomarkers and plasma lipid profiles measured sequentially (6, 24 and 72 h) in a fluid-resuscitated rat model of fecal peritonitis were compared against those measured in 27 septic patients on Days 1-3 of ICU admission. In separate studies, rat hearts were excised at the same time points for measurement of cardiomyocyte membrane cholesterol and downstream adrenergic signaling. In a final study, the impact of a 15-hour infusion of cholesterol, either given as HDL-cholesterol or liposomal cholesterol, commencing at 6 h post-sepsis induction, on dobutamine responsiveness and cardiomyocyte membrane cholesterol levels was assessed.

resultsThe magnitude of fall in stroke volume, rise in heart rate, plasma troponin and BNP, and fall in plasma HDL-cholesterol on ICU Day 1 in septic patients and at 6 h in the rat model all prognosticated for poor outcomes. In parallel, cardiomyocyte membrane cholesterol fell in the rats, more so in poor prognosis animals, with a blunted inotropic response to dobutamine, indicative of SIM. Cholesterol administration restored cardiomyocyte membrane cholesterol, dobutamine responsiveness and adrenergic signaling.

conclusionsIn a long-term rat model of sepsis, that parallels changes seen in septic patients, cardiomyocyte membrane cholesterol fell with associated decreases in catecholamine responsiveness. These features could be restored by cholesterol infusion, suggesting potential utility as a therapeutic.

Indexed as

CardiomyopathiesCholesterolDobutamineSepsisAgedAnimalsBiomarkersCell MembraneDisease Models, AnimalFemaleHeart RateHumansInfusions, IntravenousMaleMiddle AgedMyocytes, CardiacBiomarkersCholesterolDobutamineCardiomyopathyCatecholamineCholesterolMyocardial depressionSepsis

Identifiers

PMID40999545
PMCPMC12465896

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.