Evidence map›Paper›PMID 26764413›Full record

Trial reportJournal of the American Heart Association2016

Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping.

Karsten Heusser, Jens Tank, Julia Brinkmann, Christoph Schroeder, Marcus May, Anika Großhennig, Daniela Wenzel, André Diedrich, Fred C G J Sweep, Heidrun Mehling and 2 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00865917 (Einfluss Selektiver I), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 20% 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.

NCT00865917 phase2unknown statusnot on this map

Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden

TypeinterventionalSponsorHannover Medical SchoolRan2008 to 2010Enrolled40ConditionsPostural Orthostatic Tachycardia SyndromeArmsbeta-blocker (Metoprolol), I(f)-blocker (ivabradine), Placebo
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
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

12 authors at 4 institutions in 3 countries.

Karsten HeusserInstitute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Jens TankInstitute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Julia BrinkmannInstitute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Christoph SchroederInstitute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Marcus MayInstitute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Anika GroßhennigInstitute of Biostatistics, Hannover Medical School, Hannover, Germany (A.G., D.W.).
Daniela WenzelInstitute of Biostatistics, Hannover Medical School, Hannover, Germany (A.G., D.W.).
André DiedrichDivision of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Service, Vanderbilt University, Nashville, TN (A.D.).
Fred C G J SweepDepartment of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands (F.J.S.).
Heidrun MehlingExperimental Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine, Berlin, Germany (H.M., F.C.L.).
Friedrich C LuftExperimental Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine, Berlin, Germany (H.M., F.C.L.).
Jens JordanInstitute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Medizinische Hochschule Hannover · DECharité - Universitätsmedizin Berlin · DERadboud University Nijmegen · NLVanderbilt University · US

Funding

Structural genomics of norepinephrine transportersP01HL056693 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BIAGGIONI, ITALO · 1997 to 2016
$30.8M
NHLBI NIH HHS P01 HL056693
6 · The paper itself

Abstract

backgroundSympathetic and parasympathetic influences on heart rate (HR), which are governed by baroreflex mechanisms, are integrated at the cardiac sinus node through hyperpolarization-activated cyclic nucleotide-gated channels (HCN4). We hypothesized that HCN4 blockade with ivabradine selectively attenuates HR and baroreflex HR regulation, leaving baroreflex control of muscle sympathetic nerve activity intact. METHODS AND

resultsWe treated 21 healthy men with 2×7.5 mg ivabradine or placebo in a randomized crossover fashion. We recorded electrocardiogram, blood pressure, and muscle sympathetic nerve activity at rest and during pharmacological baroreflex testing. Ivabradine reduced normalized HR from 65.9±8.1 to 58.4±6.2 beats per minute (P<0.001) with unaffected blood pressure and muscle sympathetic nerve activity. On ivabradine, cardiac and sympathetic baroreflex gains and blood pressure responses to vasoactive drugs were unchanged. Ivabradine aggravated bradycardia during baroreflex loading.

conclusionsHCN4 blockade with ivabradine reduced HR, leaving physiological regulation of HR and muscle sympathetic nerve activity as well as baroreflex blood pressure buffering intact. Ivabradine could aggravate bradycardia during parasympathetic activation. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00865917.

Indexed as

AdultAutonomic Nervous SystemBaroreflexBenzazepinesBiological ClocksBlood PressureBradycardiaCardiovascular AgentsCross-Over StudiesDouble-Blind MethodElectrocardiographyGermanyHealthy VolunteersHeart RateHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsBenzazepinesCardiovascular AgentsHCN4 protein, humanHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIvabradineMuscle ProteinsPotassium Channelsautonomic nervous systembaroreflex controlfunny channelheart ratehemodynamicsinhibitormicroneurographypharmacologyphysiologysinoatrial node

Identifiers

PMID26764413
PMCPMC4859385
OpenAlexW2236201726

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.