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Editors
D. Neil Granger, Louisiana State Universi Editors
D. Neil Granger, Louisiana State University Health Sciences Center-Shreveport
Joey P. Granger, University of Mississippi Medical Center
Physiology is a scientific discipline devoted to understanding the functions of the body. It addresses
function at multiple levels, including molecular, cellular, organ, and system. An appreciation of the
processes that occur at each level is necessary to understand function in health and the dysfunction associated with disease. Homeostasis and integration are fundamental principles of physiology
that account for the relative constancy of organ processes and bodily function even in the face of
substantial environmental changes. This constancy results from integrative, cooperative interactions
of chemical and electrical signaling processes within and between cells, organs, and systems. This
eBook series on the broad field of physiology covers the major organ systems from an integrative perspective that addresses the molecular and cellular processes that contribute to homeostasis.
Material on pathophysiology is also included throughout the eBooks. The state-of the-art treatises
were produced by leading experts in the field of physiology. Each eBook includes stand-alone information and is intended to be of value to students, scientists, and clinicians in the biomedical
sciences. Since physiological concepts are an ever-changing work-in-progress, each contributor will
have the opportunity to make periodic updates of the covered material.
R. John Solaro
Department of Physiology and Biophysics
University of Illinois at Chicago
College of Medicine
Chicago, IL
Abstract
Contractility describes the relative ability of the heart to eject a stroke volume (SV) at a given prevailing afterload (arterial pressure) and preload (end-diastolic volume; EDV). Various measures of
contractility are related to the fraction as the SV/EDV or the ejection fraction, and the dynamics
of ejection as determined from maximum pressure rise in the ventricles or arteries or from aortic
flow velocities determined by echocardiography. At the cellular level, the ultimate determinant of
contractility is the relative tension generation and shortening capability of the molecular motors
(myosin cross-bridges) of the sarcomeres as determined by the rates and extent of Ca activation,
the turnover kinetics of the cross-bridges, and the relative Ca responsiveness of the sarcomeres.
Engagement of the regulatory signaling cascades controlling contractility occurs with occupancy
and signal transduction by receptors for neurohumors of the autonomic nervous system as well as
growth and stress signaling pathways. Contractility is also determined by the prevailing conditions
of pH, temperature, and redox state. Short-term control of contractility is fully expressed during
exercise. In long-term responses to stresses on the heart, contractility is modified by cellular remodeling and altered signaling that may compensate for a time but which ultimately may fail, leading
to disorders.
Contractility in the modern context
The use of the term contractility goes back well over a 125 years, and was used to simply describe a
property of assorted tissues to shorten. The term has something to do with the ability of heart tissue
to shorten, but has taken on new connotations in current thinking. Moreover, with the state of detailed knowledge of molecular and cellular control of the level of activity and dynamics of the heart,
assigning a strict definition does not seem appropriate inasmuch as the relative performance of the
heart may take on different dimensions including the relative peak pressure in the cardiac chambers
at relatively constant volume (peak tension in an isometric contraction of muscle fibers), changes in
the rate of pressure (tension) development, and the slope of the relation between chamber volume
and chamber end systolic pressure. There has also been the designation of changes in contractility
as promoted by extrinsic control mechanisms such as neuro-humoral signaling in contrast to those
promoted by intrinsic control mechanisms such as the end diastolic fiber length (Frank-Starling
relation). As will be evident here, consideration of the mechanism by which contractility is controlled indicates that this is an artificial separation. Whatever the case, it is apparent that the term
contractility remains useful to permit succinct written and oral communication between and among
scientists and clinicians. However, as described here, detailed understanding of the control mechanisms altering contractility in health and disease demands flexibility in the interpretation of the
meaning of a statement regarding the relative contractility of the heart. In approaching this detailed
understanding, we first consider the pressure and volume dynamics of the heart beat and how these
change with changes in contractility. These altered dynamics constrain theories as to the mechanisms accounting for altered contractility at the molecular and cellular levels. We then discuss current understanding of these molecular and cellular mechanisms. In considering these mechanisms,
we focus on the left ventricle (LV). Chapters in monographs
REGULATION OF CARDIAC CONTRACTILITY
Control of Contractility Is at the
Cellular Level of Organization
Control of Contractility is at the Cellular Level of Organization
REGULATION OF CARDIAC CONTRACTILITY
Control of Contractility is at the Cellular Level of Organization
Left Ventricular Diastolic and
Systolic Pressure, Ejection, and
Relaxation Reflect Sarcomeric
Mechanical Properties
sarcomeric mechanical properties
REGULATION OF CARDIAC CONTRACTILITY
sarcomeric mechanical properties
Integration of Sarcomere Mechanics
with Cardiac Function Clarifies the
Meaning of Preload, Afterload,
and Contractility
Integration of Sarcomere Mechanics
REGULATION OF CARDIAC CONTRACTILITY
Pressure Volume Loops Provide a
Quantification of Contractility
Pressure Volume Loops Provide a Quantification of Contractility
Phosphorylations of Regulatory Proteins
in Excitation Contraction Coupling
Modify Contractility by Controlling
Cellular Ca2+ Fluxes, the Response of
the Myofilaments to Ca2+, and the
Kinetics of the Cross-Bridge Cycle
Phosphorylations of Regulatory Proteins
Contractility May Be Altered by a Variety
of Mechanisms Not Involving a
Prominent Role for the Autonomic
Nervous System
Cardiac Function Curves Provide a
Compact Graphical Representation of
Regulation of CO and SV
Cardiac Function Curves
Heart Failure as a Failure
of Contractility
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