ArticleThe Journal of clinical investigation1993
Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart.
Article in The Journal of clinical investigation, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
151 citing papers in PubMed, 1 synthesis or guideline pooled it, 712 citations in OpenAlex.
- Periodontitis and the Risk of Heart Failure:a Meta-analysis and Mendelian Randomisation Study.Oral health & preventive dentistry · 2025Pooled it
- Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression.Intensive care medicine · 2005Trial
- JNK2 Is a Stress Integrator Driving Atrial Fibrillation Pathogenesis in Aging via Gut-Heart Crosstalk.Circulation · 2026Article
- Immune dysregulation as a key driver of peripartum cardiomyopathy - an exploratory advanced imaging and biomarker study.European journal of heart failure · 2025Article
- Immunometabolism in heart failure.Nature reviews. Cardiology · 2025Review
- Epicardial Adipose Tissue-A Novel Therapeutic Target in Obesity Cardiomyopathy.International journal of molecular sciences · 2025Review
- Spatial transcriptional landscape of human heart failure.European heart journal · 2025Article
- Left ventricular myocardial functions in pediatric patients with primary nephrotic syndrome: a comprehensive evaluation using conventional echocardiography, two-dimensional speckle tracking, and three-dimensional echocardiography.Italian journal of pediatrics · 2025Observational
- Cardiometabolic diseases in patients with inflammatory bowel disease: An evidence-based review.World journal of gastroenterology · 2025Review
- Implications of Oxidative Stress in the Pathophysiological Pathways of Heart Failure.International journal of molecular sciences · 2025Review
- Cardiovascular Disease in HIV Patients: A Comprehensive Review of Current Knowledge and Clinical Implications.International journal of molecular sciences · 2025Review
- Investigating the NF-κB signaling pathway in heart failure: Exploring potential therapeutic approaches.Heliyon · 2024Review
- The Emerging Specialty of Cardio-Rheumatology.Current atherosclerosis reports · 2024Review
- APLAID complicated with arrhythmogenic dilated cardiomyopathy caused by a novel PLCG2 variant.Immunologic research · 2024Article
- The role of pyroptosis in heart failure and related traditional chinese medicine treatments.Frontiers in pharmacology · 2024Review
- Cardiovascular manifestations of inflammatory bowel diseases and the underlying pathogenic mechanisms.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Review
- CRAT links cholesterol metabolism to innate immune responses in the heart.Nature metabolism · 2023Article
- Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease.Nature reviews. Rheumatology · 2023Review
- Levosimendan in the Treatment of Patients with Severe Septic Cardiomyopathy.Life (Basel, Switzerland) · 2023Article
- Tumor Necrosis Factor Family Members and Myocardial Ischemia-Reperfusion Injury: State of the Art and Therapeutic Implications.International journal of molecular sciences · 2023Review
91 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
To define the mechanism(s) responsible for the negative inotropic effects of tumor necrosis factor-alpha (TNF alpha) in the adult heart, we examined the functional effects of TNF alpha in the intact left ventricle and the isolated adult cardiac myocyte. Studies in both the ventricle and the isolated adult cardiac myocyte showed that TNF alpha exerted a concentration- and time-dependent negative inotropic effect that was fully reversible upon removal of this cytokine. Further, treatment with a neutralizing anti-TNF alpha antibody prevented the negative inotropic effects of TNF alpha in isolated myocytes. A cellular basis for the above findings was provided by studies which showed that treatment with TNF alpha resulted in decreased levels of peak intracellular calcium during the systolic contraction sequence; moreover, these findings did not appear to be secondary to alterations in the electrophysiological properties of the cardiac myocyte. Further studies showed that increased levels of nitric oxide, de novo protein synthesis, and metabolites of the arachidonic acid pathway were unlikely to be responsible for the TNF alpha-induced abnormalities in contractile function. Thus, these studies constitute the initial demonstration that the negative inotropic effects of TNF alpha are the direct result of alterations in intracellular calcium homeostasis in the adult cardiac myocyte.
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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.