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Heart failure and Starling's Law of the heart
1Faculty of Medicine, University of Calgary, Alberta.
Insights
Heart failure impairs the heart's ability to pump blood due to molecular changes in cardiac cells, particularly affecting calcium handling and cellular response to stretch. This leads to reduced force generation and impaired relaxation, crucial for effective cardiac function.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Coronary artery disease and ischemic myocardial damage are leading causes of heart failure.
- Heart failure results from impaired cardiac contractility and relaxation, often linked to molecular changes in cardiac cells.
- Excitation-contraction coupling is vital for controlling heartbeat force.
Purpose of the Study:
- To provide an overview of the mechanisms involved in excitation-contraction coupling in the context of heart failure.
- To explain how molecular changes in cardiac cells contribute to the reduced pumping efficiency in heart failure.
- To discuss the role of calcium ion handling, cellular stiffness, and receptor sensitivity in the pathophysiology of heart failure.
Main Methods:
- Review of existing literature on cardiac excitation-contraction coupling.
- Analysis of molecular mechanisms underlying impaired contractility and relaxation in heart failure.
- Discussion of the impact of calcium ion dynamics, sarcomere length sensitivity, and receptor function on cardiac performance.
Main Results:
- Heart failure involves impaired calcium ion release and uptake by the sarcoplasmic reticulum, reducing contractile force.
- Loss of sensitivity to sarcomere length (Starling's Law) and reduced maximal shortening velocity are observed in heart failure.
- Downregulation of beta-1 receptors and impaired signaling diminish the heart's response to sympathetic stimulation.
Conclusions:
- Molecular derangements in calcium handling and cellular mechanics are central to heart failure pathophysiology.
- Impaired excitation-contraction coupling, reduced responsiveness to stretch, and diminished beta-adrenergic signaling contribute to cardiac dysfunction.
- Understanding these mechanisms is crucial for developing effective therapeutic strategies for heart failure.
Abstract:
Coronary artery disease and ischemic myocardial damage form the most common cause of failure of the heart to pump enough blood for oxygenation of the body at a healthy blood pressure and at a low pressure in the veins. This paper gives an overview of the mechanisms involved in excitation-contraction coupling which are important to control of the force of the heartbeat. The inability of the heart in failure to eject a sufficient amount of blood in order to meet the needs of the body is thought to result from molecular changes in cardiac cells causing decreased active (systolic) force and impaired (diastolic) relaxation together with a greater stiffness of the remodelled ventricular wall. The failure to generate a forceful contraction is in part a consequence of derailment of the processes in the failing cardiac cells to manipulate calcium ions, despite the increased stimulus from nervous and hormone systems to enhance cardiac performance. By lack of adequate release and uptake of calcium ions, the amount of mechanical work that can be put out by the heart muscle is diminished and the heart may fail. Uptake of calcium ions by the intracellular store-the sarcoplasmic reticulum-is impaired in congestive heart failure probably as result of inadequate gene expression. In consequence, the amount of calcium that is released during each heartbeat is less than normal, thus force is reduced; in addition, the positive response of force to increased heart rate is lost. In normal heart muscle, the response of the contractile filaments to calcium ions depends strongly on sarcomere length thus explaining Starling's Law of the heart. Recent evidence suggests that this sensitivity is largely lost in congestive heart failure thereby reducing the effectiveness of stretch of cardiac cells on the mechanical output. The reduction of the maximal velocity of shortening of the cardiac sarcomere in heart failure is not well understood, but may in part be related to changes in the internal load as a result of changes in visco-elastic components of the myocardium Lastly, the effect of longstanding sympathetic drive to the heart during the development of heart failure induces a loss of sensitivity of the myocardium to catecholamines by loss of beta 1 receptors and partial uncoupling of the beta receptors from production of cyclic AMP; hence the effect of sympathetic activation is diminished and the heart has to rely more on Starling's Law. Increase of the filling pressure of the left ventricle may in part accommodate the ongoing demands of the body. However, in the case of a stenosed coronary arterial system, the increased end-diastolic pressure carries the substantial risk of aggravating pre-existent myocardial ischemia.