Evidence mapPaperPMID 37634134Full record

ArticleEuropean heart journal2024

Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

Santeri Tarvainen, Galina Wirth, Greta Juusola, Olli Hautero, Kari Kalliokoski, Tanja Sjöros, Veikko Nikulainen, Jouni Taavitsainen, Jarkko Hytönen, Crister Frimodig and 10 more

Open access · hybridAbstract read
In one paragraph

Article in European heart journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
6.7field-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

12 citing papers in PubMed, 21 citations in OpenAlex.

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  10. Cuproptosis and copper deficiency in ischemic vascular injury and repair.Apoptosis : an international journal on programmed cell death · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 1 country.

Santeri TarvainenHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Galina WirthHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Greta JuusolaHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Olli HauteroTurku University Hospital, Turku, Finland.
Kari KalliokoskiTurku University Hospital, Turku, Finland.
Tanja SjörosTurku University Hospital, Turku, Finland.
Veikko NikulainenTurku University Hospital, Turku, Finland.
Jouni TaavitsainenHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Jarkko HytönenHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Crister FrimodigHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Krista HapponenHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Tuomas SelanderResearch Services, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Tomi LaitinenImaging Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Harri H HakovirtaTurku University Hospital, Turku, Finland.
Juhani KnuutiTurku University Hospital, Turku, Finland.ORCID 0000-0003-3156-9593
Nihay Laham-KaramA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Juha HartikainenHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.ORCID 0000-0003-0847-107X
Kimmo MäkinenHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.
Seppo Ylä-HerttualaHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.ORCID 0000-0001-7593-2708
Petra KorpisaloHeart Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland.ORCID 0000-0002-5088-8939
University of Eastern Finland · FIKuopio University Hospital · FIÅbo Akademi University · FITurku University Hospital · FIUniversity of Turku · FI

Funding

European Research Council 884382
6 · The paper itself

Abstract

BACKGROUND AND

aimsClinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology.

methodsClinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome.

resultsResting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle.

conclusionsThese findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.

Indexed as

Peripheral Arterial DiseaseAnimalsChronic DiseaseHumansHypoxiaIschemiaRabbitsRetrospective StudiesRisk FactorsTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor AAngiogenesisCapillariesChronic limb-threatening ischaemiaGrowth factorHypoxiaIschaemiaMicrovascular remodellingPeripheral arterial diseaseVascular endothelial

Identifiers

PMID37634134
PMCPMC10821383
OpenAlexW4386203854

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.