Evidence map›Paper›PMID 26123012›Full record

ArticleJournal of the American Society of Echocardiography : official publication of the American Society of Echocardiography2015

Abnormal Regulation of Microvascular Tone in a Murine Model of Sickle Cell Disease Assessed by Contrast Ultrasound.

Melinda D Wu, J Todd Belcik, Yue Qi, Yan Zhao, Cameron Benner, Hong Pei, Joel Linden, Jonathan R Lindner

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans.American journal of physiology. Heart and circulatory physiology · 2016
    Trial
  2. Review
  3. 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

8 authors at 2 institutions in 1 country.

Melinda D WuDivision of Pediatric Hematology and Oncology, Oregon Health & Science University, Portland, Oregon.
J Todd BelcikKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Yue QiKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Yan ZhaoKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Cameron BennerKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Hong PeiLa Jolla Immunology and Allergy Institute, La Jolla, California.
Joel LindenLa Jolla Immunology and Allergy Institute, La Jolla, California.
Jonathan R LindnerKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon. Electronic address: lindnerj@ohsu.edu.
Oregon Health & Science University · USLa Jolla Institute for Immunology · US

Funding

Targeted CEU Imaging of Atherosclerosis and AngiogenesisR01HL078610 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LINDNER, JONATHAN R · 2004 to 2022
$6.8M
Augmentation of Tissue Perfusion with Ultrasound-mediated CavitationR01HL130046 · NHLBI · UNIVERSITY OF VIRGINIA · PI LINDNER, JONATHAN R · 2016 to 2023
$5.5M
Biomarkers of Inflammation and Vaso-occlusion in Sickle Cell DiseaseR01HL111969 · NHLBI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI FIELD, JOSHUA JEFFREY, LINDEN, JOEL M. · 2012 to 2016
$4.0M
Training in Translational Science and Cardiovascular MedicineT32HL094294 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ALKAYED, NABIL J · 2009 to 2018
$3.5M
Lymphocyte Activation in Sickle Cell Lung DiseaseR01HL095704 · NHLBI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI LINDEN, JOEL M. · 2010 to 2014
$2.3M
NHLBI NIH HHS R01 HL078610NHLBI NIH HHS R01-HL078610NHLBI NIH HHS R01 HL095704NHLBI NIH HHS R01-HL095704NHLBI NIH HHS R01 HL111969NHLBI NIH HHS R01-HL111969NHLBI NIH HHS R01 HL130046NHLBI NIH HHS T32 HL094294NHLBI NIH HHS T32-HL-94294-5
6 · The paper itself

Abstract

backgroundMicrovascular dysregulation, abnormal rheology, and vaso-occlusive events play a role in the pathophysiology of sickle cell disease (SCD). The aim of this study was to test the hypothesis that abnormalities in skeletal muscle perfusion in a murine model of SCD could be parametrically assessed by quantitative contrast-enhanced ultrasound perfusion imaging.

methodsA murine model of moderate SCD without anemia produced by homozygous β-globin deletion replaced by human βs-globin transgene (NY1DD-/-; n = 18), heterozygous transgene replacement (NY1DD+/-; n = 19), and C57Bl/6 control mice (n = 14) was studied. Quantitative contrast-enhanced ultrasound of the proximal hindlimb skeletal muscle was performed at rest and during contractile exercise (2 Hz). Time-intensity data were analyzed to measure microvascular blood volume (MBV), microvascular blood transit rate (β), and microvascular blood flow. Erythrocyte deformability was measured by elongation at various rotational shears.

resultsAt rest, muscle MBV was similar between strains, whereas β was significantly (P = .0015, analysis of variance) reduced to a similar degree in NY1DD-/- and NY1DD+/- compared with wild-type mice (0.24 ± 0.10, 0.16 ± 0.07, and 0.34 ± 0.14 sec(-1), respectively), resulting in a reduction in microvascular blood flow. During contractile exercise, there were no groupwise differences in β (1.43 ± 0.67, 1.09 ± 0.42, and 1.36 ± 0.49 sec(-1) for NY1DD-/-, NY1DD+/-, and wild-type mice, respectively) or in microvascular blood flow or MBV. Erythrocyte deformability at high shear stress (≥5 Pa) was mildly reduced in both transgenic groups, although it was not correlated with blood flow or β.

conclusionsContrast-enhanced ultrasound in skeletal muscle revealed a lower microvascular blood transit rate in the NY1DD model of SCD and sickle trait but no alterations in MBV. The abnormality in microvascular blood transit rate was likely due to vasomotor dysfunction, because it was abrogated by contractile exercise and at rest was only weakly related to erythrocyte deformability.

Indexed as

Contrast MediaAnemia, Sickle CellAnimalsDisease Models, AnimalMiceMice, Inbred C57BLMicrocirculationMuscle ContractionMuscle, SkeletalRegional Blood FlowUltrasonographyVascular ResistanceContrast MediaContrast ultrasoundEchocardiographySickle cell disease

Identifiers

PMID26123012
PMCPMC4567487
OpenAlexW1860290216

What OpenQuestion holds

Textmetadata
LicenceTDM
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.