Related Experiment Video

Updated: Aug 12, 2026

Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice
09:05

Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice

Published on: May 4, 2015

Inflammatory mediators and the failing heart: past, present, and the foreseeable future

Douglas L Mann1

  • 1Winters Center for Heart Failure Research, the Cardiology Section, Department of Medicine, Veterans Administration Medical Center, Methodist Hospital, and Baylor College of Medicine, Houston, Tex 77030, USA. dmann@bcm.tmc.edu

Circulation Research
|November 29, 2002
PubMed

Insights

Targeting tumor necrosis factor (TNF) to treat heart failure has unexpectedly worsened patient outcomes. Future research must re-evaluate the role of proinflammatory cytokines in heart failure pathogenesis.

Area of Science:

  • Cardiology
  • Immunology
  • Biomedical Science

Background:

  • Proinflammatory mediators are increasingly recognized for their role in heart failure development and progression.
  • Preclinical and clinical models highlighted the pathophysiological impact of sustained proinflammatory mediator expression.

Purpose of the Study:

  • To review the current understanding of proinflammatory mediators in heart failure.
  • To analyze insights gained from recent negative clinical trials targeting tumor necrosis factor (TNF).
  • To discuss potential future research directions in this field.

Main Methods:

  • Literature review focusing on preclinical and clinical studies of heart failure.
  • Analysis of multicenter clinical trials investigating TNF neutralization in heart failure patients.
  • Synthesis of knowledge regarding the role of proinflammatory cytokines in heart failure pathogenesis.

Main Results:

  • Clinical trials targeting TNF in moderate to advanced heart failure unexpectedly led to worsened heart failure.
  • These negative outcomes challenge the established understanding of TNF's role in heart failure.
  • The results necessitate a re-evaluation of the therapeutic strategies targeting inflammation in heart failure.

Conclusions:

  • The role of proinflammatory cytokines, specifically TNF, in heart failure pathogenesis requires further investigation.
  • Negative clinical trial results provide critical lessons for future therapeutic development.
  • Future research should explore alternative or refined strategies for modulating inflammation in heart failure.

More Related Videos

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure09:37

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Published on: December 2, 2014

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs14:35

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs

Published on: April 17, 2021

Related Concept Videos

Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
Ischemic Heart Disease: Overview01:17

Ischemic Heart Disease: Overview

Ischemic heart disease occurs when the heart's blood supply dwindles, causing an ominous lack of oxygen and nutrients. This deficiency, stemming from reduced or obstructed blood flow, spells danger, leading to heart muscle damage and dysfunction.
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and narrowing...
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
Heart Failure I: Introduction01:27

Heart Failure I: Introduction

Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
Heart Failure V: Medical Management01:30

Heart Failure V: Medical Management

Medical Management of Acute Decompensated Heart Failure (ADHF)The primary goals of therapy for patients hospitalized with acute decompensated heart failure (ADHF) include:Relieving symptomsOptimizing volume statusSupporting oxygenation and ventilationMaintaining cardiac output (CO) and end-organ perfusionIdentifying and addressing the cause of ADHFPreventing complicationsProviding patient education on factors precipitating HF exacerbationPlanning for dischargeOngoing monitoring and assessment...