Evidence map›Paper›PMID 41779942›Full record

ArticleASAIO journal (American Society for Artificial Internal Organs : 1992)2026

Acellular Hemoglobin Impairs Cardiomyocyte Excitation-Contraction Coupling.

Daniela Lucas, Carlos Munoz, Cynthia R Muller, Xiangming Gu, Savannah R Wolfe, Clayton T Cuddington, Andre F Palmer, Pedro Cabrales

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ASAIO journal (American Society for Artificial Internal Organs : 1992), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Daniela LucasFrom the Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, California.ORCID 0009-0005-0101-4628
Carlos MunozFrom the Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, California.ORCID 0000-0003-4832-3661
Cynthia R MullerFrom the Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, California.ORCID 0000-0003-4698-8168
Xiangming GuWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio.ORCID 0000-0001-9096-5911
Savannah R WolfeWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio.ORCID 0000-0001-9806-9492
Clayton T CuddingtonWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio.ORCID 0000-0001-8739-2155
Andre F PalmerWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio.ORCID 0000-0002-3378-3772
Pedro CabralesFrom the Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, California.

Funding

Bioengineering a Dual Function Protein Construct to Detoxify Heme and HemoglobinR01HL159862 · NHLBI · OHIO STATE UNIVERSITY · PI BUEHLER, PAUL WERNER, CABRALES, PEDRO · 2021 to 2024
$2.6M
Bioengineering a novel therapeutic protein complex to minimize the effects of medical device induced hemolysisR01HL162120 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BUEHLER, PAUL WERNER, CABRALES, PEDRO · 2022 to 2025
$2.6M
Attenuating the Oxidative and Myocardial Side-Effects of Acellular HemoglobinR01HL126945 · NHLBI · OHIO STATE UNIVERSITY · PI CABRALES, PEDRO, PALMER, ANDRE FRANCIS · 2016 to 2019
$1.7M
Training in Bioengineering Research and Technology Development in Cardiovascular in Cardiopulmonary Health and DiseaseT32HL160507 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Karen L Christman, Andrew D. McCulloch · 2022 to 2026
$1.6M
NHLBI NIH HHS R01 HL126945NHLBI NIH HHS R01 HL159862NHLBI NIH HHS R01 HL162120NHLBI NIH HHS T32 HL160507
6 · The paper itself

Abstract

Heart failure is a significant complication of chronic intravascular hemolysis, a condition characterized by red blood cells (RBCs) breakdown, leading to the release of acellular hemoglobin (Hb) and its oxidized form, methemoglobin (MetHb), into the bloodstream. Acellular Hb promotes nitric oxide (NO) scavenging, oxidative stress, inflammation, iron overload, and functional tissue impairment. This study investigates the direct impact of Hb and MetHb on cardiomyocyte function by assessing calcium transients, fractional shortening, and reactive oxygen species (ROS) formation. The study also evaluated the effects of polymerized Hb, NO scavenging, and antioxidant therapy using N-acetylcysteine (NAC) on cardiomyocyte contractility. Our results show that acellular Hb and MetHb impair cardiomyocyte function by prolonging calcium transient half-life, reducing contractility, and increasing ROS production. Polymerization of Hb and antioxidant supplementation offered partial protection but did not fully mitigate these effects. Inhibiting NO synthase did not increase Hb toxicity, indicating that NO scavenging is not the sole toxicity pathway. These findings demonstrate that Hb-induced cardiomyocyte dysfunction involves a multifactorial mechanism, including NO scavenging, oxidative stress, and disrupted calcium dynamics. Although Hb polymerization and antioxidants offer limited protection, novel multi-target strategies are essential to address Hb toxicity in hemolytic disorders and the use of Hb-based oxygen carriers.

Indexed as

cardiomyocyte dysfunctionexcitation-contraction couplinghemoglobinhemolysisoxidative stress

Identifiers

PMID41779942
PMCPMC13574302

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.