DETERMINANTS OF VENTRICULAR PERFORMANCE
Discussions of ventricular function usually refer to the left ventricle, but the same concepts apply to the right ventricle. Although the ventricles are often thought of as functioning separately, their interde-pendence has clearly been demonstrated. Moreover, factors affecting systolic and diastolic functions can be differentiated: Systolic function involves ventric-ular ejection, whereas diastolic function is related to ventricular filling.
Ventricular systolic function is often (errone-ously) equated with cardiac output, which can be defined as the volume of blood pumped by the heart per minute. Because the two ventricles function in series, their outputs are normally equal. Cardiac out-put (CO) is expressed by the following equation:
CO = SV × HR
where SV is the stroke volume (the volume pumped per contraction) and HR is heart rate. To compensate for variations in body size, CO is often expressed in terms of total body surface area:
where CI is the cardiac index and BSA is body sur-face area. BSA is usually obtained from nomograms
based on height and weight (Figure 20–3). Normal CI is 2.5–4.2 L/min/m2. Because the normal CI has a wide range, it is a relatively insensitive measurement of ventricular performance. Abnormalities in CI therefore usually reflect gross ventricular impairment. A more accurate assess-ment can be obtained if the response of the cardiac output to exercise is evaluated. Under these condi-tions, failure of the cardiac output to increase and keep up with oxygen consumption is reflected by a decreasing mixed venous oxygen saturation. A decrease in mixed venous oxygen saturation in response to increased demand usually reflects inadequate tissue perfusion. Thus, in the absence of hypoxia or severe anemia, measurement of mixed venous oxygen tension (or satura-tion) is an excellent estimate of the adequacy of cardiac output.
When stroke volume remains constant, cardiac out-put is directly proportional to heart rate. Heart rate is an intrinsic function of the SA node (spontane-ous depolarization), but is modified by autonomic, humoral, and local factors. The normal intrinsic rate of the SA node in young adults is about 90– 100 beats/min, but it decreases with age based on the following formula:
Normal intrinsic heart rate = 118 beats/min − (0.57 × age)
Enhanced vagal activity slows the heart rate via stimulation of M 2 cholinergic receptors, whereas enhanced sympathetic activity increases the heart rate mainly through activation of β1-adrenergic receptors and, to lesser extent, β2-adrenergic recep-tors (see above).
Stroke volume is normally determined by three major factors: preload, afterload, and contractility. This analysis is analogous to laboratory observa-tions on skeletal muscle preparations. Preload is muscle length prior to contraction, whereas after-load is the tension against which the muscle must
contract. Contractility is an intrinsic property of the muscle that is related to the force of contrac-tion but is independent of both preload and after-load. Because the heart is a three-dimensional multichambered pump, both ventricular geometric form and valvular dysfunction can also affect stroke volume (Table 20–3).
Ventricular preload is end-diastolic volume, which is generally dependent on ventricular filling. The relationship between cardiac output and left ven-tricular end-diastolic volume is known as Starling’s law of the heart (Figure 20–4). Note that when the heart rate and contractility remain constant, car-diac output is directly proportional to preload until excessive end-diastolic volumes are reached. At that
point, cardiac output does not appreciably change— or may even decrease. Excessive distention of either ventricle can lead to excessive dilatation and incom-petence of the AV valves.
Ventricular fi lling can be influenced by a variety of factors (Table 20–4), of which the most impor-tant is venous return. Because most of the other
factors affecting venous return are usually fixed, vascular capacity is normally its major determi-nant. Increases in metabolic activity reduce vas-cular capacity, so that venous return to the heart increases as the volume of venous capacitance vessels decreases. Changes in blood volume and venous tone are important causes of intraopera-tive and postoperative changes in ventricular fill-ing and cardiac output. Any factor that alters the normally small venous pressure gradient favoring blood return to the heart also affects cardiac filling. Such factors include changes in intrathoracic pres-sure (positive-pressure ventilation or thoracotomy), posture (positioning during surgery), and pericar-dial pressure (pericardial disease).
The most important determinant of right ven-tricular preload is venous return. In the absence of significant pulmonary or right ventricular dys-function, venous return is also the major deter-minant of left ventricular preload. Normally, the end-diastolic volumes of both ventricles are similar,and, normally, the venous return is numerically equivalent to the cardiac output.
Both heart rate and rhythm can also affect ven-tricular preload. Increases in heart rate are associ-ated with proportionately greater reductions in diastole than systole. Ventricular filling therefore progressively becomes impaired at increased heart rates (>120 beats/min in adults). Absent (atrial fibrillation), ineffective (atrial flutter), or altered timing of atrial contraction (low atrial or junctional rhythms) can also reduce ventricular filling by 20% to 30%. Patients with reduced ventricular compliance are more affected by the loss of anormally timed atrial systole than are those with normal ventricular compliance.
Left ventricular end-diastolic pressure (LVEDP) can be used as a measure of preload only if the relationship between ventricular volume and pressure (ventricular compliance) is constant. However, ventricular compliance is normally non-linear (Figure 20–5). Impaired diastolic function reduces ventricular compliance. Therefore, the same LVEDP that corresponds to a normal preload in a normal patient may correspond to a decreased pre-load in a patient with impaired diastolic function.
Many factors are known to influence ventricular diastolic function and compliance. Nonetheless, measurement of LVEDP or other pressures approx-imating LVEDP (such as pulmonary artery occlu-sion pressure) are potential means of estimating left ventricular preload. Changes in central venous pressure can be used as a rough index for changes in right and left ventricular preload in most normal individuals.
Factors affecting ventricular compliance can be separated into those related to the rate of relax-ation (early diastolic compliance) and passive stiffness of the ventricles (late diastolic compli-ance). Hypertrophy (from hypertension or aortic valve stenosis), ischemia, and asynchrony reduce early compliance; hypertrophy and fibrosis reduce late compliance. Extrinsic factors (such as pericar-dial disease, excessive distention of the contralat-eral ventricle, increased airway or pleural pressure, tumors, and surgical compression) can also reduce ventricular compliance. Because of its normally thinner wall, the right ventricle is more compliant than the left.
Afterload for the intact heart is commonly equated with either ventricular wall tension during systole or arterial impedance to ejection. Wall tension may be thought of as the pressure the ventricle must over-come to reduce its cavity volume. If the ventricle is assumed to be spherical, ventricular wall tension can be expressed by Laplace’s law:
where P is intraventricular pressure, R is the ven-tricular radius, and H is wall thickness. Although the normal ventricle is usually ellipsoidal, this relationship is still useful. The larger the ventricu-lar radius, the greater the wall tension required to develop the same ventricular pressure. Conversely, an increase in wall thickness reduces ventricular wall tension.
Systolic intraventricular pressure is dependent on the force of ventricular contraction; the visco-elastic properties of the aorta, its proximal branches,
and blood (viscosity and density); and systemicvascular resistance (SVR). Arteriolar tone is theprimary determinant of SVR. Because viscoelastic properties are generally fixed in any given patient, left ventricular afterload is usually equated clini-cally with SVR, which is calculated by the following equation:
where MAP is mean arterial pressure in millime-ters of mercury, CVP is central venous pressure in millimeters of mercury, and CO is cardiac output in liters per minute. Normal SVR is 900–1500 dyn · s cm–5. Systolic blood pressure may also be used as an approximation of left ventricular afterload in the absence of chronic changes in the size, shape, or thickness of the ventricular wall or acute changes in systemic vascular resistance. Some clinicians prefer to use CI instead of CO in calculating a systemic vas-cular resistance index (SVRI), so that SVRI = SVR × BSA.
Right ventricular afterload is mainly depen-dent on pulmonary vascular resistance (PVR) and is expressed by the following equation:
where PAP is mean pulmonary artery pressure and LAP is left atrial pressure. In practice, pulmonary capillary wedge pressure (PCWP) is usually substi-tuted as an approximation for LAP. Normal PVR is 50–150 dyn · s cm–5.
Cardiac output is inversely related to large changes in afterload on the left ventricle; however, small increases or decreases in afterload may have no effect at all on cardiac output. Because of its thinner wall, the right ventricle is more sensitive to changes in afterload than is the left ventricle.Cardiac output in patients with marked right or left ventricular impairment is verysensitive to acute increases in afterload. The latter is particularly true in the presence of drug- or ischemia-induced myocardial depression or chronic heart failure.
Cardiac contractility (inotropy) is the intrinsic ability of the myocardium to pump in the absence of changes in preload or afterload. Contractility is related to the rate of myocardial muscle shortening, which is, in turn, dependent on the intracellular Ca2+ concentration during systole. Increases in heart rate can also enhance contractility under some condi-tions, perhaps because of the increased availability of intracellular Ca 2+.
Contractility can be altered by neural, humoral, or pharmacological influences. Sympathetic nervous system activity normally has the most important effect on contractility. Sympathetic fibers innervate atrial and ventricular muscle, as well as nodal tissues. In addition to its positive chronotropic effect, norepi-nephrine release also enhances contractility primar-ily via β1-receptor activation. α-Adrenergic receptors are also present in the myocardium, but seem to have only minor positive inotropic and chronotropic effects. Sympathomimetic drugs and secretion of epi-nephrine from the adrenal glands similarly increase contractility via β1-receptor activation.
Myocardial contractility is depressed by hypoxia, acidosis, depletion of catecholamine stores within the heart, and loss of functioning muscle mass as a result of ischemia or infarction. At large enough doses, most anesthetics and antiarrhyth-mic agents are negative inotropes (ie, they decrease contractility).
Regional wall motion abnormalities cause a break-down of the analogy between the intact heart and skeletal muscle preparations. Such abnormalities may be due to ischemia, scarring, hypertrophy, or altered conduction. When the ventricular cavity does not collapse symmetrically or fully, emptying becomes impaired. Hypokinesis (decreased contrac-tion), akinesis (failure to contract), and dyskinesis (paradoxic bulging) during systole reflect increasing degrees of contraction abnormalities. Although con-tractility may be normal or even enhanced in some areas, abnormalities in other areas of the ventricle can impair emptying and reduce stroke volume. The severity of the impairment depends on the size and number of abnormally contracting areas.
Valvular dysfunction can involve any one of the four valves in the heart and can include stenosis, regur-gitation (incompetence), or both. Stenosis of an AV valve (tricuspid or mitral) reduces stroke volume primarily by decreasing ventricular preload, whereas stenosis of a semilunar valve (pulmonary or aortic) reduces stroke volume primarily by increasing ven-tricular afterload. In contrast, valvular regurgita-tion can reduce stroke volume without changes in preload, afterload, or contractility and without wall motion abnormalities. The effective stroke volume is reduced by the regurgitant volume with every con-traction. When an AV valve is incompetent, a sig-nificant part of the ventricular end-diastolic volume can flow backward into the atrium during systole; the stroke volume is reduced by the regurgitant vol-ume. Similarly, when a semilunar valve is incompe-tent, a fraction of end-diastolic volume arises from backward flow into the ventricle during diastole.