Load-sensitive diastolic relaxation in hypertrophied left ventricles
W Hayashida1, J Donckier, H Van Mechelen
1Department of Physiology and Pharmacology, University of Louvain School of Medicine, Brussels, Belgium.
The American Journal of Physiology
|March 5, 1998
Summary
Enalaprilat and L-158,809 improved diastolic relaxation in dogs with heart. These drugs may benefit hypertrophied hearts by targeting the renin-angiotensin system.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Left ventricular hypertrophy (LVH) is associated with impaired diastolic relaxation.
- The renin-angiotensin system plays a role in the development of LVH and diastolic dysfunction.
Purpose of the Study:
- To investigate the effects of enalaprilat (an ACE inhibitor) and L-158,809 (an angiotensin II type-1 receptor antagonist) on left ventricular (LV) diastolic relaxation in a canine model of LVH.
- To determine if these agents can improve load-sensitive diastolic abnormalities in LVH.
Main Methods:
- Studied 11 normal control dogs and 16 LVH dogs with perinephritic hypertension.
- Assessed LV diastolic relaxation using the time constant of relaxation under varying loading conditions induced by vena caval occlusion.
- Administered enalaprilat and L-158,809 and re-evaluated LV relaxation.
Main Results:
- LVH dogs exhibited impaired diastolic relaxation, evidenced by a prolonged relaxation time constant.
- LV unloading worsened diastolic dysfunction in LVH dogs, making relaxation load-sensitive.
- Both enalaprilat and L-158,809 significantly improved the load-sensitive diastolic relaxation abnormality in LVH dogs.
- Neither drug affected LV relaxation in normal control dogs.
Conclusions:
- Angiotensin II contributes to diastolic dysfunction in pressure-overloaded LVH.
- Angiotensin-converting enzyme inhibitors and angiotensin II type-1 receptor antagonists show potential therapeutic benefits for the hypertrophied heart.
- Targeting the renin-angiotensin system may be a viable strategy for treating diastolic dysfunction in LVH.
Related Concept Videos
01:26Imbalances in Cardiac Output
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 blood...
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 blood...
01:20Mitral Regurgitation I: Introduction
Mitral regurgitation is characterized by the backward circulation of blood from the left ventricle to the left atrium during systole, a phase of the cardiac cycle when the heart contracts and pumps blood out of the chambers. This abnormal flow occurs primarily due to the dysfunction of the mitral valve or its supporting structures, which include the mitral leaflets, chordae tendineae, annulus, and papillary muscles.Etiology and Mechanisms:Primary Mitral Regurgitation: This type arises from...
01:22Mitral Stenosis I: Introduction
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...
01:22Aortic Regurgitation II: Clinical Features and Diagnostic Tests
Aortic valve regurgitation (AR) occurs when the aortic valve fails to close properly, allowing blood to flow backward from the aorta into the left ventricle. This backflow can result in two distinct clinical presentations: acute and chronic AR, each characterized by its own set of symptoms and physical findings.Acute Aortic RegurgitationAcute AR presents with a sudden onset of severe symptoms. Patients typically experience profound dyspnea (shortness of breath), chest pain, and signs of left...
01:29Heart 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...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...