Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles
Cheavar A Blair1, Elizabeth A Brundage2, Katherine L Thompson3
1Department of Physiology, University of Kentucky, Lexington, Kentucky.
JACC. Basic to Translational Science
|September 3, 2020
Summary
Heart failure significantly reduces human heart muscle force and power, impacting both ventricles. Contractile changes are linked to remodeling and altered calcium sensitivity, with distinct effects between the left and right ventricles.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Heart failure (HF) is a complex syndrome characterized by impaired cardiac function.
- Understanding the impact of HF on myocardial contractile properties is crucial for developing targeted therapies.
- Ventricular remodeling, including fibrosis and cellular disarray, is a hallmark of HF.
Purpose of the Study:
- To investigate the effects of heart failure on the contractile properties of human left and right ventricular myocardium.
- To explore the role of calcium (Ca2+) sensitivity and troponin I phosphorylation in HF-associated contractile dysfunction.
- To determine if adrenergic stimulation elicits differential responses in the left and right ventricles during heart failure.
Main Methods:
- Measurement of maximum force and maximum power in multicellular myocardial preparations from human ventricles.
- Assessment of calcium (Ca2+) sensitivity of contraction.
- Analysis of troponin I phosphorylation patterns.
- Comparison of contractile properties between left and right ventricular samples.
Main Results:
- Maximum force and power were reduced by approximately 30% in both ventricles, likely due to remodeling.
- Heart failure increased Ca2+ sensitivity of contraction, with a more pronounced effect in the right ventricle.
- Ventricle-specific changes in troponin I phosphorylation were observed, correlating with altered Ca2+ sensitivity.
Conclusions:
- Heart failure significantly impairs human ventricular contractile function, reducing maximum force and power.
- Altered calcium sensitivity and ventricle-specific changes in troponin I phosphorylation are key mechanisms in HF.
- Differential responses to adrenergic stimulation between the left and right ventricles warrant further investigation in heart failure.
Keywords:
Ca2+ sensitivityCa2+, calciumFact, maximum Ca2+-activated forceFpas, passive forceLV, left ventricleMyBP-C, myosin binding protein-CPKA, protein kinase APmax, maximum power outputRLC, regulatory light chainRV, right ventricleTnI, troponin IVmax, maximum shortening velocityheart failurehuman myocardiumktr, rate of force recoverymyofilament proteinsnH, Hill coefficientventricular function
Related Concept Videos
01:29Heart Failure II: Pathophysiology
523
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...
523
01:26Imbalances in Cardiac Output
2.0K
The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
2.0K
01:17Pathophysiology of Heart Failure
2.4K
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...
2.4K
01:27Heart Failure I: Introduction
563
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...
563
01:22Mitral Stenosis I: Introduction
215
Mitral Valve Stenosis (MVS) is a heart condition where the mitral valve narrows, impeding blood circulation from the left atrium to the left ventricle. The etiology and pathophysiology of this condition are multifaceted, leading to a cascade of cardiovascular complications.Causes of Mitral Valve StenosisRheumatic Heart Disease: It is the main cause of mitral valve stenosis, particularly in developing nations. This condition arises from rheumatic fever, an inflammatory illness resulting from...
215
01:22Heart Failure Drugs: β-Blockers
621
β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
621