Evidence map›Paper›PMID 26846552›Full record

ArticleJournal of applied physiology (Bethesda, Md. : 1985)2016

Pharmacological targeting of mitochondrial reactive oxygen species counteracts diaphragm weakness in chronic heart failure.

Orlando Laitano, Bumsoo Ahn, Nikhil Patel, Philip D Coblentz, Ashley J Smuder, Jeung-Ki Yoo, Demetra D Christou, Peter J Adhihetty, Leonardo F Ferreira

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of applied physiology (Bethesda, Md. : 1985), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF.Frontiers in cardiovascular medicine · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Cardiac Rehab for Functional Improvement.Current heart failure reports · 2020
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Mitochondrial respiration and HAmerican journal of physiology. Cell physiology · 2019
    Article
  19. Article
  20. 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

9 authors at 1 institution in 1 country.

Orlando LaitanoDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Bumsoo AhnDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Nikhil PatelDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Philip D CoblentzDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Ashley J SmuderDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Jeung-Ki YooDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Demetra D ChristouDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Peter J AdhihettyDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Leonardo F FerreiraDepartment of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida ferreira@hhp.ufl.edu.
University of Florida · US

Funding

Redox basis of diaphragm mitochondrial dysfunction and atrophy in heart failureR01HL130318 · NHLBI · UNIVERSITY OF FLORIDA · PI FERREIRA, LEONARDO · 2016 to 2025
$3.9M
Mechanisms of Respiratory Muscle Dysfunction in Heart FailureR00HL098453 · NHLBI · UNIVERSITY OF FLORIDA · PI FERREIRA, LEONARDO · 2011 to 2013
$735k
NHLBI NIH HHS R00-HL-098453NHLBI NIH HHS R01 HL130318
6 · The paper itself

Abstract

Diaphragm muscle weakness in chronic heart failure (CHF) is caused by elevated oxidants and exacerbates breathing abnormalities, exercise intolerance, and dyspnea. However, the specific source of oxidants that cause diaphragm weakness is unknown. We examined whether mitochondrial reactive oxygen species (ROS) cause diaphragm weakness in CHF by testing the hypothesis that CHF animals treated with a mitochondria-targeted antioxidant have normal diaphragm function. Rats underwent CHF or sham surgery. Eight weeks after surgeries, we administered a mitochondrial-targeted antioxidant (MitoTEMPO; 1 mg·kg(-1)·day(-1)) or sterile saline (Vehicle). Left ventricular dysfunction (echocardiography) pre- and posttreatment and morphological abnormalities were consistent with the presence of CHF. CHF elicited a threefold (P < 0.05) increase in diaphragm mitochondrial H2O2 emission, decreased diaphragm glutathione content by 23%, and also depressed twitch and maximal tetanic force by ∼20% in Vehicle-treated animals compared with Sham (P < 0.05 for all comparisons). Diaphragm mitochondrial H2O2 emission, glutathione content, and twitch and maximal tetanic force were normal in CHF animals receiving MitoTEMPO. Neither CHF nor MitoTEMPO altered the diaphragm protein levels of antioxidant enzymes: superoxide dismutases (CuZn-SOD or MnSOD), glutathione peroxidase, and catalase. In both Vehicle and MitoTEMPO groups, CHF elicited a ∼30% increase in cytochrome c oxidase activity, whereas there were no changes in citrate synthase activity. Our data suggest that elevated mitochondrial H2O2 emission causes diaphragm weakness in CHF. Moreover, changes in protein levels of antioxidant enzymes or mitochondrial content do not seem to mediate the increase in mitochondria H2O2 emission in CHF and protective effects of MitoTEMPO.

Indexed as

AnimalsAntioxidantsDiaphragmElectron Transport Complex IVGlutathioneGlutathione PeroxidaseHeart FailureHydrogen PeroxideMitochondriaMuscle WeaknessOxidation-ReductionOxidative StressRatsRats, WistarReactive Oxygen SpeciesSuperoxidesAntioxidantsElectron Transport Complex IVGlutathioneGlutathione PeroxidaseHydrogen PeroxideReactive Oxygen SpeciesSuperoxidesforceinspiratory musclemycardial infarctionoxidantsskeletal muscle

Identifiers

PMID26846552
PMCPMC4824042
OpenAlexW2292462159

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.