Evidence map›Paper›PMID 25172950›Full record

Trial reportThe Journal of physiology2014

Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine.

Niklas Telinius, Sheyanth Mohanakumar, Jens Majgaard, Sukhan Kim, Hans Pilegaard, Einar Pahle, Jørn Nielsen, Marc de Leval, Christian Aalkjaer, Vibeke Hjortdal and 1 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

41 citing papers in PubMed, 65 citations in OpenAlex.

  1. Octreotide improves human lymphatic fluid transport a translational trial.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2024
    Trial
  2. Pacemaking in the lymphatic system.The Journal of physiology · 2026
    Review
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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

11 authors at 3 institutions in 1 country.

Niklas TeliniusDepartment of Biomedicine, Aarhus University, Aarhus, Denmark Department of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark telinius@me.com.
Sheyanth MohanakumarDepartment of Biomedicine, Aarhus University, Aarhus, Denmark Department of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark.
Jens MajgaardDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Sukhan KimDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Hans PilegaardDepartment of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark.
Einar PahleDepartment of Surgery, Viborg Hospital, Viborg, Denmark.
Jørn NielsenDepartment of Surgery, Viborg Hospital, Viborg, Denmark.
Marc de LevalInternational Congenital Cardiac Centre, Harley Street Clinic, London, UK.
Christian AalkjaerDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Vibeke HjortdalDepartment of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark.
Donna Briggs BoedtkjerDepartment of Biomedicine, Aarhus University, Aarhus, Denmark Department of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark.
Aarhus University · DKAarhus University Hospital · DKRegionshospitalet Viborg · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity. Nifedipine also inhibited spontaneous action potentials measured by sharp microelectrodes. Furthermore, noradrenaline did not elicit normal increases in lymphatic vessel tone when maximal constriction was reduced to 29.4 ± 4.9% of control in the presence of 20 nmol l(-1) nifedipine. Transcripts for the L-type calcium channel gene CACNA1C were consistently detected from human thoracic duct samples examined and the CaV1.2 protein was localized by immunoreactivity to lymphatic smooth muscle cells. While human lymphatics ex vivo were highly sensitive to nifedipine, this was not apparent in vivo when nifedipine was compared to placebo in a randomized, double-blinded clinical trial: conversely, lymphatic vessel contraction frequency was increased and refill time was faster despite all subjects achieving target nifedipine plasma concentrations. We conclude that human lymphatic vessels are highly sensitive to nifedipine in vitro but that care must be taken when extrapolating in vitro observations of lymphatic vessel function to the clinical situation, as similar changes in lymphatic function were not evident in our clinical trial comparing nifedipine treatment to placebo.

Indexed as

AdultAgedAged, 80 and overCalcium Channel BlockersCalcium Channels, L-TypeCross-Over StudiesGene Expression RegulationHumansLymphedemaMaleMembrane PotentialsMiddle AgedMuscle ContractionMyocytes, Smooth MuscleNifedipineThoracic DuctCalcium Channel BlockersCalcium Channels, L-TypeNifedipine

Identifiers

PMID25172950
PMCPMC4253471
OpenAlexW1509053484

What OpenQuestion holds

Textmetadata
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.