Evidence map›Paper›PMID 27642642›Full record

ArticleJACC. Basic to translational science

Kinetics and Signal Activation Properties of Circulating Factor(s) From Healthy Volunteers Undergoing Remote Ischemic Pre-Conditioning.

Heike A Hildebrandt, Vincent Kreienkamp, Sabine Gent, Philipp Kahlert, Gerd Heusch, Petra Kleinbongard

Open access · goldAbstract read
In one paragraph

Article in JACC. Basic to translational science. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Guideline
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  8. The spleen in ischaemic heart disease.Nature reviews. Cardiology · 2025
    Review
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  12. Isolated Perfused Hearts for Cardiovascular Research: An Old Dog with New Tricks.Journal of cardiovascular translational research · 2024
    Review
  13. Article
  14. Article
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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

6 authors at 1 institution in 1 country.

Heike A HildebrandtInstitute for Pathophysiology, West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany; Department of Cardiology of the West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany.
Vincent KreienkampInstitute for Pathophysiology, West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany.
Sabine GentInstitute for Pathophysiology, West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany.
Philipp KahlertDepartment of Cardiology of the West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany.
Gerd HeuschInstitute for Pathophysiology, West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany.
Petra KleinbongardInstitute for Pathophysiology, West-German Heart and Vascular Center Essen, University of Essen Medical School, Essen, Germany.
West German Heart and Vascular Center Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although remote ischemic pre-conditioning (RIPC) reduced infarct size in animal experiments and proof-of-concept clinical trials, recent phase III trials failed to confirm cardioprotection during cardiac surgery. Here, we characterized the kinetic properties of humoral factors that are released after RIPC, as well as the signal transduction pathways that were responsible for cardioprotection in an ex vivo model of global ischemia reperfusion injury. Venous blood from 20 healthy volunteers was collected at baseline and 5 min, 30 min, 1 h, 6 h, and daily from 1 to 7 days after RIPC (3 × 5/5 min upper-limb ischemia/reperfusion). Plasma-dialysates (cut-off: 12 to 14 kDa; dilution: 1:20) were infused into Langendorff-perfused mouse hearts subjected to 20/120 min global ischemia/reperfusion. Infarct size and phosphorylation of signal transducer and activator of transcription (STAT)3, STAT5, extracellular-regulated kinase 1/2 and protein kinase B were determined. In a subgroup of plasma-dialysates, an inhibitor of STAT3 (Stattic) was used in mouse hearts. Perfusion with baseline-dialysate resulted in an infarct size of 39% of ventricular mass (interquartile range: 36% to 42%). Perfusion with dialysates obtained 5 min to 6 days after RIPC significantly reduced infarct size by ∼50% and increased STAT3 phosphorylation beyond that with baseline-dialysate. Inhibition of STAT3 abrogated these effects. These results suggest that RIPC induces the release of cardioprotective, dialyzable factor(s) within 5 min, and that circulate for up to 6 days. STAT3 is activated in murine myocardium by RIPC-induced human humoral factors and is causally involved in cardioprotection.

Indexed as

AKT, protein kinase BcardioprotectionERK, extracellular-regulated kinasehumanhumoral factorIQR, interquartile rangekineticsLVDP, left ventricular developed pressureLV+RV, left and right ventricularremote ischemic pre-conditioningRIC, remote ischemic conditioningRIPC, remote ischemic pre-conditioningSAFE, survival activating factor enhancementsignalingSTAT, signal transducer and activator of transcriptionTTC, 2,3,5-triphenyltetrazolium chloride

Identifiers

PMID27642642
PMCPMC5012372
OpenAlexW2321727237

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.