Each myocyte is surrounded by a connective tissue framework called the endomysium. Groups of myocytes are joined within the perimysium, and the entire muscle within the epimysium. Muscle bundles are anchored in the fibrous skeleton at the base of the heart. Muscle bundles spiral around the cavity in overlapping patterns.
The geometry of each ventricle is adapted to the function required of it. The left ventricle, which must eject against high pressure, is conical in shape with inlet and outlet adjacent at the base of the cone. Cavity volume is reduced during systole by a combination of concentric contraction and wall thickening, the latter predominating. The right ventricle wraps around the left ventricle, its cavity is crescent shaped with separated points of inflow and outflow. Cavity reduction is primarily a result of concentric contraction of the right ventricular free wall against the septum.
Clinically Measureable Physiologic Parameters
Cardiac surgeons can assess the function of the heart in a number of ways. Aortic, pulmonary artery, pulmonary capillary wedge, and central venous pressures can be measured directly. Cardiac output can be estimated using thermodilution or based on oxygen saturation measurements. From these direct measurements, other parameters can be derived—although less accurate because of the cumulative error of the measured parameters inherent in the calculation—such as pulmonary and systemic vascular resistance, and ventricular stroke work. Ejection fraction—defined as stroke volume/end-diastolic volume—can be estimated by echocardiography and ventriculography, but is subject to change based on loading conditions, heart rate, and degree of contractility. Although clinically useful, these parameters do not directly measure contractility.
The Frank-Starling Relationship
Within physiologic limits, the heart functions as a sump pump. The more the heart is filled during diastole, the greater the quantity of blood that will be pumped out of the heart during systole. Under normal circumstances, the heart pumps all the blood that comes back to it without excessive elevation of venous pressures. In the normal heart, as ventricular filling is increased, the strength of ventricular contraction increases. The influence of sarcomere length on the force of contraction is called the Frank-Starling relationship. This relationship for the left ventricle is depicted in Fig. 3-9. Also depicted in Fig. 3-9 are two other states, a condition of normal adrenergic stimulation and a condition of maximal adrenergic stimulation. Force is increased for the same resting conditions by adrenergic stimulation; this is a positive inotropic effect.
Starling curves for the left ventricle. The influence of four different states of neurohumoral stimulation on global ventricular performance is shown.
Preload: Diastolic Distensibility and Compliance
Preload is the load placed on a resting muscle that stretches it to its functional length. In the heart, preload references the volume of blood in the cavity immediately prior to contraction (at end-diastole) because volume determines the degree of stretch imposed on the resting sarcomere. As volume cannot be easily assessed clinically, pressure is used as a surrogate; thus, the concept of preload is represented as the filling pressure of a chamber. The relationship between the end-diastolic pressure and the end-diastolic volume is complex. Several different diastolic pressure-volume relationships are shown in Fig. 3-11 (bold line). As end-diastolic volume increases, and the heart stretches, the end-diastolic pressure also increases. The compliance, or distensibility of the ventricle, is defined as the change in volume divided by the change in pressure. Conversely, the stiffness of the ventricle is the reciprocal of compliance, or the change in pressure divided by the change in volume.
Left ventricular pressure-volume curves for various physiologic and pathologic conditions. (Detailed descriptions are in the text.) The bold curved line at the bottom of each loop series represents the diastolic pressure-volume relationship. The straight line located on the upper left side of each loop series is the end-systolic pressure-volume relationship. The stroke volume for each curve has been arbitrarily set at 75 mL. Systolic aortic pressure is 115 mm Hg in all curves except B (increased afterload, systolic pressure 140 mm Hg) and H (reduced afterload, systolic pressure 90 mm Hg) (EF = ejection fraction; LV = left ventricle; LVEDP = left ventricular end-diastolic pressure), in mm Hg.
A number of factors affect the diastolic pressure-volume relationship. A fibrotic heart, a hypertrophied heart, or an aging heart becomes increasingly stiff (Figs. 3-11C and 3-11E). In the case of fibrosis, this increasing stiffness is related to the development of a greater collagen network. In the case of hypertrophy, this increased stiffness is related both to stiffening of the noncontractile components of the heart and also to impaired relaxation of the heart. Relaxation is an active, energy-requiring process. This process is accelerated by catecholamine stimulation, but is impaired by ischemia, hypothyroidism, and chronic congestive heart failure. Examination of the diastolic pressure-volume curves in Fig. 3-11 reveals the importance of changes in diastolic distensibility in pathologic cardiac conditions.
Afterload: Vascular Impedance
The afterload of an isolated muscle is the tension against which it contracts. In simplest terms, for the heart, the afterload is determined by the pressure against which the ventricle must eject. The greater the afterload, the more mechanical energy that must be imparted to the blood mass (potential energy) to begin ejection. In addition to the potential energy imparted to the ejected blood by a change in pressure, the contracting left ventricle generates kinetic energy which overcomes the compliance of the distensible aorta and systemic arterial tree to move the blood into the arterial system. The energy necessary for this flow to occur is relatively small (potential energy >> kinetic energy). Resistance, which equals the change in pressure divided by cardiac output, reflects the potential energy imparted to blood. To accurately describe the forces overcome to eject blood from the ventricle, the compliance of the vascular system and kinetic energy imparted must also be considered: the impedance of the vascular system (commonly, but less accurately referred to as aortic impedance). Compliance reflects the capacity of the vascular system to accept the volume of ejected blood. When the vascular system is very compliant; resistance ≈ impedance. As compliance decreases (eg, with arteriosclerosis), resistance is less than impedance.29 The interaction of resistance and compliance define the dicrotic notch, marking end-systole, closure of the aortic valve, on the aortic pressure tracing (Fig. 3-10).
Temporal correlation of left atrial and ventricular, aortic, and systemic venous pressures, aortic flow, left ventricular volume and surface electrocardiogram.
Multiple parameters of the cardiac cycle are represented in Fig. 3-10. By convention the cardiac cycle begins at end-diastole (ED), just prior to electrical activation of the ventricle. As the heart contracts, intracavitary pressure closes the mitral valve, then rapidly increases until the systemic diastolic pressure is reached (isovolumic contraction) and the aortic valve opens. Ejection begins and the intracavitary pressure continues to rise then fall as the ventricular volume decreases (ejection). When ejection ceases and the aortic valve closes, intracavitary pressure decreases rapidly until the mitral valve opens (isovolumic relaxation). Once the mitral valve opens, the ventricle fills rapidly, then more slowly as the intracavitary pressure slightly increases from distension prior to atrial systole (diastolic filling phase). The completion of atrial systole is the end of ventricular diastole. Atrial systole serves to increase the preload of the ventricle at a given systemic venous pressure.
A conceptual understanding of the venous pressure changes is important in diagnosing certain pathologic processes. The right atrial pressure is easily measured and pulmonary capillary wedge pressure is reflective of left atrial pressure. The “a” wave corresponds to atrial systole as pressure increases at end-diastole to complete ventricular filling. The “c” wave reflects pressure pushing the atrioventricular (AV) valve back into the atrium as the ventricular pressure rises then falls during systole. The “x” descent results from atrial relaxation and downward displacement of the AV valve with ventricular emptying. The “v” wave reflects the increasing atrial pressure from filling before the AV valve opens. The “y” descent is caused by rapid emptying of the atrium after the AV valve opens. Characteristic changes in these waveforms are used to diagnose and differentiate constrictive and restrictive processes, as discussed elsewhere in the text. A prominent left atrial “v” wave suggests mitral regurgitation.
Ventricular Pressure-Volume Relationships
The function of the heart can be described and quantified based on the relative intraventricular pressure and volume during the cardiac cycle (Fig. 3-11). Based on this relationship, various measures can be derived to assess cardiac performance. The ventricular pressure-volume relationship derives from the Frank-Starling relationship of sarcomere length and peak developed force: The force and extent of contraction (stroke volume) is a function of end-diastolic length (volume).
End-diastole (ED) is represented at the lower right corner of the loop in Fig. 3-11A. The pressure volume loop then successively tracks changes through isovolumic contraction (up to the upper right corner); ejection (left to the upper left corner, which represents end-systole [ES]); isovolumic relaxation (down to the bottom left corner); then filling (right to the lower right corner). Descriptive data to assess ventricular function are derived from the end-systolic pressure-volume point located in the upper left corner of the loop, and end-diastolic pressure-volume point located in the lower right corner of the loop. The area within the pressure-volume loop represents the internal work of the chamber.
The term contractility (inotropic state) refers to the intrinsic performance of the ventricle for a given preload, afterload, and heart rate. Otherwise stated, all the factors that impact cardiac performance independent of the acute effects of preload, afterload, and heart rate. In the purest sense, at a level of constant contractility, increased preload will increase cardiac output and stroke volume; increased afterload will decrease cardiac output and stroke volume; and increased heart rate (assuming adequate time for complete diastolic filling) will increase cardiac output without changing stroke volume. Although the inotropic state impacts cardiac output, it is difficult to quantify in clinically useful terms. For research purposes, the pressure-volume relationship can be used to quantify contractility by deriving the end-systolic pressure-volume relationship (ESPVR): Contractility is reflected in the slope (EES) and volume axis intercept (V0) of the ESPVR (Fig. 3-12). Holding afterload and heart rate constant, a series of pressure-volume loops are inscribed during transient preload reduction induced by temporary vena caval occlusion; the area of the loops decreases and the loops are shifted to the left. The progressive pressure-volume points at end systole are then linearized to derive the ESPVR. Within a clinical range of systolic pressures (80 to 120 mm Hg), the end-systolic pressure-volume line is largely linear. An increase in inotropic state of the left ventricle is expressed as an increase in EES and sometimes a decrease in V0. Conversely, a decrease in inotropic state is expressed as a decrease in EES and sometimes an increase in V0 (see Fig. 3-12). As the ESPVR describes systolic function, the end-diastolic pressure volume relationship (EDPVR) (see Fig. 3-12) describes ventricular diastolic compliance (more specifically, the inverse of the slope of the EDPVR is compliance) a measure of lusitropy. The EDPVR is impacted by calcium uptake, ease of dissociation of contractile proteins, the cytoskeleton, ventricular wall thickness, and the pericardium.
Two series of declining left ventricular pressure-volume loops generated during transient bicaval occlusion. Loops were generated in normal left ventricles (normal) and after 30 minutes of global normothermic ischemia and subsequent reperfusion (dashed lines). The end-systolic pressure-volume points from each series are connected by a line generated by linear regression. The end-diastolic pressure-volume relationship indicating chamber stiffness (inverse of compliance) is generated by fitting the end-diastolic point from each loop to an exponential curve. The volume axis intercept (V0) is shown in the inset. A negative inotropic effect (ie, ischemia-reperfusion) is characterized by a decrease in the ESPVR slope, while a positive inotropic state is characterized by an increase in ESPVR slope. Notice that the V0 for these conditions are in close proximity (inset). In some cases, a negative inotropic state is associated with a decrease in slope and an increase in V0.
Pressure-volume loops can be used to analyze various physiologic situations. Increased afterload (see Fig. 3-11B) moves the end-systolic pressure-volume point slightly upward and to the right. If stroke volume is maintained, end-diastolic volume must increase. Thus, though contractility is unchanged, ejection fraction is slightly decreased. Figure 3-11C shows the effect of a decrease in ventricular compliance (increased EDPVR) such as may result from hypertrophy, fibrosis, or cardiac tamponade. Systolic function is maintained (EES and V0 are unchanged), and stroke volume and ejection fraction can be maintained but require an increased end-diastolic pressure. The positive inotropic (increased EES) and lusitropic (decreased EDPVR) effects of adrenergic stimulation (see Fig. 3-11D), at constant stroke volume, shift the pressure-volume loop to the left, and increase the ejection fraction. In the hypertrophied heart (see Fig. 3-11E), in contrast to Fig. 3-11C, diastolic compliance is decreased and systolic contractility is increased. A constant stroke volume leads to an increase in end-diastolic filling pressure and decreased end-diastolic volume. The pressure-volume loop shifts to the left with an increase in ejection fraction. The ability of the hypertrophied heart to increase stroke volume is limited. Acute ischemia (see Fig. 3-11F) decreases diastolic compliance (increases EDPVR) and contractility. The pressure-volume loop shifts to the right and up to maintain stroke volume, consistent with the clinical observation of an acute decrease in ejection fraction and increase in left ventricular filling pressure. In the dilated heart of chronic congestive heart failure (see Fig. 3-11G) the pressure-volume loop is shifted to the right. Note that the slope of the diastolic pressure-volume curve (EDPVR) changes little, rather the curve shifts to the right. The end-diastolic pressure is not increased because of a change in compliance; instead, to maintain stroke volume, the pressure-volume loop has moved upward on the compliance curve. Contrast this with the fibrotic process discussed in the preceding. The effect of afterload reduction on the chronically failing heart from Fig. 3-11G is demonstrated in Fig. 3-11H. Note that the ESPVR, EDPVR, and stroke volume are unchanged. The pressure volume loop has moved back to the left, decreasing both the degree of chamber dilatation, end-diastolic pressure, and ejection fraction. A positive inotropic agent would shift the ESPVR line to the left (toward the dashed line), and the degree of dilatation would be reduced and both stroke volume and ejection fraction would be increased. It is important to remember that these relationships are idealized and may not completely reflect true clinical responses. For example, reduced diastolic dilatation from afterload reduction could return the ventricle to a state of improved intrinsic contractility. Despite these interactions, the pure concepts discussed here are very helpful in understanding the response of the heart to clinical interventions.
Another index of contractility, perhaps less influenced by other parameters, is the preload recruitable stroke work (PRSW) relationship. Stroke work is the area of the pressure-volume loop. For each pressure-volume loop derived by vena caval occlusion, the stroke work is plotted relative to its end-diastolic volume (Fig. 3-13).30 The slope of the derived linear relationship is a measure of contractility independent (within physiologic ranges) of preload and afterload. The PRSW relationship reflects overall performance of the left ventricle, combining systolic and diastolic components.31
Plot of hypothetical measurement of preload recruitable stroke work.
Clinical Indices of Contractility
Clearly, from the preceding discussion, the degree of contractility can be assessed, but unlike blood pressure, an ideal number or range to describe it cannot be derived. Because ESPVR and PRSW are unique for each ventricle, these parameters more accurately measure changes in contractility. The greatest impediment to the clinical application of the ESPVR and PRSW is the difficulty measuring ventricular volume and inducing preload reduction to derive the pressure-volume loops. More easily measurable indices of contractility have been actively sought.
Ejection fraction is used by many clinicians as a measure of contractility. However, as noted in the discussion of Fig. 3-11, ejection fraction is influenced by preload and afterload alterations without any change in contractility. Depending on loading conditions, hearts with a lower ejection fraction can produce a greater cardiac output. Although roughly indicative of cardiac reserve, ejection fraction is an inconsistent marker for overall cardiac function perioperatively but is a useful, gross measure of cardiac reserve.
The left ventricle is a pressurized, irregularly shaped chamber. During systole, wall stress develops to overcome afterload and eject the blood. The pressure within the chamber and the geometry of the ventricle determine the tension in the wall. A model of the ventricle as a cylinder can be used to examine the effects of chamber size and wall thickness on wall stress. In this model, circumferential stress is based on the law of LaPlace
where σ is wall stress (≈ tension), P is transmural pressure, r is radius and w is wall thickness. This relationship has several important clinical implications. Wall tension must be balanced by the energy available. The only nutrient nearly completely extracted from the blood by the heart is oxygen and wall tension is the primary determinant of oxygen consumption. In one scenario, the heart can compensate for changes in wall stress. If systolic pressure within the ventricle is chronically increased (aortic stenosis or systemic hypertension), then compensatory hypertrophy or thickening of the ventricular wall can return systolic wall stress close to normal. However, as detailed in Fig. 3-11E, the price paid is that end-diastolic pressures must be higher.
In another scenario, the function of a heart that has dilated for other reasons is further compromised by the relationship between wall stress and oxygen consumption. As a result of or to compensate for systolic failure, the ventricle will dilate. The increased diastolic diameter proportionally increases wall stress and oxygen consumption. The ability of the heart to increase cardiac output in response to exercise will be limited, leading to symptoms.