Ventricular Mechanics

Myocyte Orientation

The orientation of myofibers is complex, with variation across both the LV wall and in different LV regions. The orientation of myofibers was first quantified by Streeter and colleagues, who measured myocyte orientation in tangential sections obtained across the LV wall of the dog heart and found a smooth transition in the helix angle (in the tangential plane relative to the horizontal) from the epicardium (−60 degrees) to the endocardium (+60 degrees). Myofiber orientation data collected by Streeter is seen in Figure 50-1 . Other studies using this histologic sampling confirmed these results in different species.

Recent advances in magnetic resonance imaging allow rapid, nondestructive assessment of muscle fibers in the entire heart. Magnetic resonance diffusion tensor imaging exploits the anisotropic diffusion of water through ordered tissues. This method has been correlated with histologically measured fiber angles and has been used to map the fiber orientation thoroughly in the entire left ventricle of a normal rabbit, goat, sheep, and human.

Laminar Organization of Myocardium

The laminar nature of the myocardium has been appreciated since the 1800s. Adjacent myocytes are organized into sheets or lamina that are three to four cells thick. Furthermore, there are extensive cleavage planes between sheets that are most apparent in the midwall of the LV where the planes are radially oriented. The laminar organization of the LV has been recently championed by Torrent-Guasp, who suggested that the LV consisted of a single, folded myocardial band. Alternatively, Lagrice and colleagues proposed a finite element–based mathematical model that represents sheet geometry. A diagram of laminar architecture of the myocardium is seen in Figure 50-2 .

Extracellular Matrix

The ECM is an important determinant of LV diastolic compliance. Scanning electron microscopy of the ECM demonstrates an extensive network of collagen fibers that are organized into three primary components. Briefly, the endomysium surrounds individual cells and groups of cells and the epimysium surrounds entire muscle groups. Perimysial fibers connect groups of cells. Perimysial fibers can be seen in Figure 50-2 A . Of note, perimysial fibers associated with papillary muscle myocardium have a coiled shape with a potentially important role in papillary muscle strength and stiffness.

Electromechanical Activation

The rhythmic electrical activation of the heart normally begins at the sinoatrial (SA) node. Electrical activation spreads rapidly over the atria, initiating atrial contraction. There is a delay while electrical activation moves slowly through the atrioventricular (AV) node. The electrical activation then propagates rapidly along the bundle of His, the right and left bundle branches and sub branches (Purkinje fibers) before initiating a coordinated ventricular contraction. The excitation of the ventricles results in the QRS complex of the electrocardiogram.

Cardiac Cycle

A plot of the ECG and left atrial, LV, and aortic pressures during the cardiac cycle is schematically illustrated in Figure 50-3 . Depolarization and contraction of the LV raises intracavitary LV pressure. First, this causes the mitral valve to close. When LV pressure exceeds the pressure in the aorta, the aortic valve opens and pressurized blood is ejected into the aorta.

At the end of ejection, LV pressure falls below aortic pressure and the aortic valve closes. Relaxation of the myocytes is locally initiated and not directly coordinated by the conduction system. As the myocytes relax, the pressure drops in the ventricle. When LV pressure falls below the pressure in the atria, the mitral valve opens and filling begins.

Pressure-Volume Loop

Pressure and volume of the left ventricle are plotted as shown in Figure 50-4 . Active contraction (systole) begins at the bottom right corner of the loop. Contraction is isovolumic until the aortic valve opens at the top right corner and the ventricle ejects. The end of systole is the upper left hand corner of the loop. Diastole is initially isovolumic until the mitral valve opens at the bottom left corner and ventricular filling begins. Ventricular filling begins at the bottom left hand corner of the loop. Ventricular filling is broken into a period of early, rapid filling, a period of slow filling (diastasis), and filling associated with atrial systole. The end of filling is the end of diastole (bottom right corner of the loop).

Pressure-Volume Analysis

Pressure-volume analysis of the cardiac cycle is a cornerstone of LV mechanics. Pressure-volume analysis of cardiac function was initially described by Otto Frank, but was initially limited by the lack of suitable methods to measure LV pressure and volume. With the development of methods including cineangiography and echocardiography in 1960s that could measure ventricular volume in vivo, there was a renewed interest in the use of pressure-volume analysis to measure diastolic and systolic function.

Since that time, cardiac imaging methods have advanced substantially. The imaging method most widely used for studying the heart is still echocardiography. An additional kind of data that can be obtained with echocardiography is the measurement of flow velocities (or at least the component of velocity along the line of the ultrasound beam), through the Doppler effect. Magnetic resonance imaging (MRI) with cardiac synchronization of the imaging can provide high-quality spatially registered images that can be used to calculate volumes; MRI is the current “gold standard” method for cardiac global function volume measurements. Computed tomography (CT) has made recent advances in imaging quality and speed, and it can also provide global function volume measures, although it is still poorer in temporal resolution than MRI and has the additional disadvantages of involving radiation exposure and the use of potentially harmful contrast agents. Because CT, MRI, and three-dimensional (3D) echocardiography build collated data sets from multiple cardiac cycles, they can be used only when hemodynamics are at steady state.

The conductance catheter is best for real-time volume measurement during changes in LV preload or afterload. However, the inability of the conductance catheter to measure absolute ventricular volume because of parallel conductance is a limitation of the method.

Pressure-volume loops remain similar unless loading or the strength of contraction (contractility) are changed. If preload or afterload are changed, such as by clamping the vena cava or aorta, and, while contractility remains the same, a family of curves are generated. The end-diastolic and end-systolic points subtend two lines. The end-diastolic line, referred to as the end-diastolic pressure-volume relationship (EDPVR) or ventricular compliance curve, is typically curvilinear. A typical EDPVR relationship is seen in Figure 50-5 A . The end-systolic line, referred to as the end-systolic pressure-volume relationship (ESPVR) or end-systolic elastance, is nearly straight. The ESPVR relationship is discussed further later.

End-Diastolic Pressure-Volume Relationship (Left Ventricular Compliance)

The EDPVR is typically described by an exponential relationship :

where P is left ventricular pressure, V is left ventricular volume, ED is end-diastole, A is an offset in left ventricular pressure, and B and α are diastolic stiffness constants. Note that a shift of the EDPVR curve upward and to the left represents an increase in diastolic chamber stiffness (decrease in compliance). A shift of the curve downward or to the right means that diastolic chamber stiffness is decreased (increase in compliance).

Of note, statistical comparison of EDPVR between subjects before and after interventions is an issue. A t test is not appropriate because it fails to take colinearity into account. A log transform allows the use of multiple linear regression, but the offset term (A) must be removed.

where P is left ventricular pressure, V is left ventricular volume, ED is end-diastole, A is an offset in left ventricular pressure, and B and α are diastolic stiffness constants. A short list of mechanical factors that combine to determine the EDPVR is seen in Box 50-1 .

Myocardial Stiffness

Myocyte and ECM stiffness (discussed earlier) are determinants of global LV diastolic function. It is now appreciated that the passive stiffness of the myocyte is dependent on the giant intracellular protein titin. As discussed previously (see Fig. 49-3 ), the Z line or disc is the center point of the I band and the attachment point of actin (thin filament). The M line is the center point of the A band (myosin; thick filaments). Titin molecules extend from the Z line to the M line. Successive titin molecules are arranged head-to-head and tail-to-tail, creating a continuous protein structure that extends the entire length of the myocyte. The majority of the titin I band region is extensible and functions as a molecular spring that develops a restoring force when the cell is streched or compressed. Titin acts as a spring that when compressed or stretched generates a restoring force. A diagram showing the structure of titin is seen in Figure 50-6 .

Myocyte Relaxation

Left ventricular relaxation is a component of early diastolic filling. LV relaxation is an energy-dependent process involving the removal of Ca ²⁺ from troponin-C, followed by the dissociation of actin and myosin cross bridges, thus allowing the myofibrils to relax and to return to their original end-diastolic length. A typical LV relaxation curve is seen in Figure 50-5 B .

LV relaxation is classically evaluated by the exponential time constant of isovolumic relaxation (T), requiring cardiac catheterization to measure LV pressure.

where P(t) is left ventricular pressure as a function of time, P _o is the pressure at the time of dP/dt _min , t is time after dP/dt _min , and T is the time constant of isovolumic pressure fall. Figure 50-5 B demonstrates how relaxation pressure ( Equation 3 ) can be subtracted from actual diastolic pressure data to obtain a corrected pressure.

Left Ventricular Torsion and Recoil

The myofiber architecture described earlier (Structure of Ventricular Tissue) causes the LV to undergo torsion during systole. The magnitude of torsion is a function of myocyte contractility. As myocyte contraction and torsion occurs, extracellular collagen matrix, and intracellular titin are compressed. Untwisting occurs in early diastole. Forty percent of the LV untwisting occurs during isovolumic relaxation.

LV untwist continues during ventricular filling. Mitral valve opening is immediately followed by the development of a pressure gradient between the LV apex and base, which determines early LV filling. The rate of untwisting is a predictor of the pressure gradient between the LV apex and base as well as the time constant of diastolic relaxation. Finally, the rate of recoil is a preload-independent assessment of LV relaxation.

Ventricular Suction

The presence of negative intracavitary LV pressure in early diastole was shown in a series of experiments in which a Starr Edwards mitral prosthesis was modified to close during diastolic filling. Data from one of Yellin's experiments in which mitral valve occlusion caused a negative LV pressure (to the right of the gray bar) is seen in Figure 50-7 .

It is now thought that ventricular suction is caused by LV untwisting and elastic recoil of the compressed myocytes in early diastole. The concept is that end-systolic volume is lower than the diastolic equilibrium volume. Consequently, and depending on the time course of myocyte relaxation, the LV generates the negative intracavitary pressure described earlier. In short, ventricular suction helps to draw blood into the chamber across the mitral valve.