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A Modern View of Heart Failure: Practical Applications of Cardiovascular Physiology

Arnold M. Katz

10.1002/cphy.cp020121

Source: Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart

Originally published: 2002

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Paradigmatic Shifts
2 Definition of Heart Failure
3 The Paradigm of Organ Physiology: The Failing Heart as a Defective Pump
3.1 Backward and Forward Failure
3.2 Systolic and Diastolic Dysfunction
3.3 Right and Left Heart Failure
3.4 The Neurohumoral Response in Heart Failure
3.5 Crossover Between Functional and Proliferative Signaling
3.6 Coupling Between the Failing Heart and the Circulation: Pressure–Volume Loops
3.7 Architectural Changes in the Failing Heart
4 The Paradigm of Biochemistry and Biophysics: The Failing Heart as a Weakly Contracting, Incompletely Relaxing Muscle
4.1 Inotropic and Lusitropic Abnormalities
4.2 Energy‐Starvation
4.3 Molecular Alterations and Architectural Changes
5 The Paradigm of Gene Expression: The Failing Heart as an Abnormal Molecular Structure
5.1 Adaptive and Maladaptive Hypertrophy
5.2 Cardiac Myocyte Phenotypes
5.3 Shape Changes in the Cells of the Overloaded Heart
5.4 Myocardial Cell Death
6 Summary and Conclusions
Figure 1. Figure 1.

Left ventricular pressure‐volume loops. A: Preload, which is generated during diastole by the venous return and atrial systole, determines the point along the end‐diastolic pressure–volume relationship (the lusitropic state) at which systole begins. After the onset of ventricular systole, the mitral valve closes and wall stress continues to increase during isovolumic contraction (A), which ends when the aortic valve opens and the ventricle meets its afterload, the aortic pressure. Aortic pressure rises and falls during ejection (B), when volume decreases. Systole ends when ventricular pressure and volume reach the end‐systolic pressure–volume relationship that describes the inotropic state of the ventricle. After aortic valve closure removes the afterload (aortic pressure) from the ventricular cavity, blood can neither enter nor leave the ventricle; as a result, relaxation begins under isovolumic conditions (C). When left ventricular pressure falls below that in the left atrium, the mitral valve opens and blood flows from the atrium into the ventricle during the filling phase (D). The cycle ends when ventricular pressure and volume reach the end‐diastolic pressure–volume relationship and the next cycle begins. B: A negative inotropic intervention shifts the end‐systolic pressure–volume relationship to the right and downward (solid curves); if afterload remains constant, stroke volume will be reduced. (The control loop and end‐systolic and end‐diastolic pressure–volume relationships are shown as dashed lines.) C: A negative lusitropic intervention shifts the end‐diastolic PV relationship to the left and upward (solid curves); if afterload remains constant, stroke volume is reduced.

From reference 54
Figure 2. Figure 2.

Schematic diagram showing key structures (Left) and calcium fluxes (Right) that control cardiac excitation‐contraction coupling and relaxation in the heart. Left: the calcium “pools” are in bold capital letters. Right: which shows the calcium fluxes between these pools, the thickness of the arrows indicates the magnitude of the calcium fluxes, while their vertical orientations describe their “energetics”: downward arrows represent passive calcium fluxes and upward arrows represent energy‐dependent active calcium transport. Most of the calcium that enters the cell from the extracellular fluid via L‐type calcium channels (arrow A) triggers calcium release from the sarcoplasmic reticulum; only a small portion directly activates the contractile proteins (arrow A1). Calcium is actively transported back into the extracellular fluid by the plasma membrane calcium pump ATPase (PMCA, arrow B1), and the Na/Ca exchanger (arrow B2); the sodium that enters the cell in exchange for calcium via the latter is pumped out of the cytosol by the sodium pump (dashed lines). Two calcium fluxes are regulated by the sarcoplasmic reticulum: calcium efflux from the subsarcolemmal cisternae via calcium release channels (arrow C) and calcium uptake into the sarcotubular network by the sarco(endo)plasmic reticulum calcium pump ATPase (arrow D). Calcium diffuses within the sarcoplasmic reticulum from the sarcotubular network to the subsarcolemmal cisternae (arrow G), where it is stored in a complex with calsequestrin and other calciumbinding proteins. Calcium binding to (arrow E) and dissociation from (arrow F) high‐affinity calcium‐binding sites of troponin C activate and inhibit the interactions of the contractile proteins. Calcium movements into and out of mitochondria (arrow H) buffer cytosolic calcium concentration. The extracellular calcium cycle consists of arrows A, B1, and B2, while the intracellular cycle involves arrows C, E, F, D, and G.

From reference 54
Figure 3. Figure 3.

Effects of changing cardiac phenotype (below) on the pressure‐volume loop (above). A: Concentric hypertrophy; B: normal; C. eccentric hypertrophy. Note that the major cause of reduced stroke volume is not a decrease in contractility (the end‐systolic pressure volume relationship), but instead, architectural changes in the ventricle.

From reference 54


Figure 1.

Left ventricular pressure‐volume loops. A: Preload, which is generated during diastole by the venous return and atrial systole, determines the point along the end‐diastolic pressure–volume relationship (the lusitropic state) at which systole begins. After the onset of ventricular systole, the mitral valve closes and wall stress continues to increase during isovolumic contraction (A), which ends when the aortic valve opens and the ventricle meets its afterload, the aortic pressure. Aortic pressure rises and falls during ejection (B), when volume decreases. Systole ends when ventricular pressure and volume reach the end‐systolic pressure–volume relationship that describes the inotropic state of the ventricle. After aortic valve closure removes the afterload (aortic pressure) from the ventricular cavity, blood can neither enter nor leave the ventricle; as a result, relaxation begins under isovolumic conditions (C). When left ventricular pressure falls below that in the left atrium, the mitral valve opens and blood flows from the atrium into the ventricle during the filling phase (D). The cycle ends when ventricular pressure and volume reach the end‐diastolic pressure–volume relationship and the next cycle begins. B: A negative inotropic intervention shifts the end‐systolic pressure–volume relationship to the right and downward (solid curves); if afterload remains constant, stroke volume will be reduced. (The control loop and end‐systolic and end‐diastolic pressure–volume relationships are shown as dashed lines.) C: A negative lusitropic intervention shifts the end‐diastolic PV relationship to the left and upward (solid curves); if afterload remains constant, stroke volume is reduced.

From reference 54


Figure 2.

Schematic diagram showing key structures (Left) and calcium fluxes (Right) that control cardiac excitation‐contraction coupling and relaxation in the heart. Left: the calcium “pools” are in bold capital letters. Right: which shows the calcium fluxes between these pools, the thickness of the arrows indicates the magnitude of the calcium fluxes, while their vertical orientations describe their “energetics”: downward arrows represent passive calcium fluxes and upward arrows represent energy‐dependent active calcium transport. Most of the calcium that enters the cell from the extracellular fluid via L‐type calcium channels (arrow A) triggers calcium release from the sarcoplasmic reticulum; only a small portion directly activates the contractile proteins (arrow A1). Calcium is actively transported back into the extracellular fluid by the plasma membrane calcium pump ATPase (PMCA, arrow B1), and the Na/Ca exchanger (arrow B2); the sodium that enters the cell in exchange for calcium via the latter is pumped out of the cytosol by the sodium pump (dashed lines). Two calcium fluxes are regulated by the sarcoplasmic reticulum: calcium efflux from the subsarcolemmal cisternae via calcium release channels (arrow C) and calcium uptake into the sarcotubular network by the sarco(endo)plasmic reticulum calcium pump ATPase (arrow D). Calcium diffuses within the sarcoplasmic reticulum from the sarcotubular network to the subsarcolemmal cisternae (arrow G), where it is stored in a complex with calsequestrin and other calciumbinding proteins. Calcium binding to (arrow E) and dissociation from (arrow F) high‐affinity calcium‐binding sites of troponin C activate and inhibit the interactions of the contractile proteins. Calcium movements into and out of mitochondria (arrow H) buffer cytosolic calcium concentration. The extracellular calcium cycle consists of arrows A, B1, and B2, while the intracellular cycle involves arrows C, E, F, D, and G.

From reference 54


Figure 3.

Effects of changing cardiac phenotype (below) on the pressure‐volume loop (above). A: Concentric hypertrophy; B: normal; C. eccentric hypertrophy. Note that the major cause of reduced stroke volume is not a decrease in contractility (the end‐systolic pressure volume relationship), but instead, architectural changes in the ventricle.

From reference 54
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Article Title: A Modern View of Heart Failure: Practical Applications of Cardiovascular Physiology
 

How to Cite

Arnold M. Katz. A Modern View of Heart Failure: Practical Applications of Cardiovascular Physiology. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 786-804. First published in print 2002. doi: 10.1002/cphy.cp020121