Some Cardiac Defects Increase the Heart's Workload, Which Causes Cardiac Hypertrophy
Cardiac defects often compromise the heart’s ability to supply the systemic organs with the blood flow they need to support their metabolism. Compensating for such a pump failure frequently requires one or both ventricles to pump more blood than normal or to pump blood at a higher pressure than normal.
These adaptations increase the workload of the heart. A persistent increase in cardiac workload leads, over several weeks, to cardiac hypertrophy. A ventricle that must pump more blood volume than normal will develop some hypertrophy, whereas a ventricle that must pump blood at a higher pressure than normal develops a huge hypertrophy. This observation is the basis for the clinical aphorism, “Pressure work is harder for the heart [i.e., causes more hypertrophy] than volume work.” To understand the physiological reason of this difference, we must delve into cardiac muscle energetics. To get started, it is useful to consider the analogous case of skeletal muscle hypertrophy in response to increased workload (physical conditioning).A skeletal muscle does work by exerting a force while shortening. The useful mechanical work (external work) done by a skeletal muscle is equal to the force developed by the contracting muscle, multiplied by the distance moved during one contraction, multiplied by the number of contractions. Therefore the external work done by a skeletal muscle can be increased by increasing the forcefulness of contraction, the distance moved, or the number of contractions. In weightlifting conditioning the emphasis is on performing a few very forceful contractions of skeletal muscle. In contrast, conditioning that involves repetitive, low-force contractions of skeletal muscle (e.g., running, swimming) emphasizes primarily the distance and duration components of skeletal muscle work. Both “weight work” and “distance work” lead to skeletal muscle hypertrophy.
However, a common observation is that weight work causes substantially more hypertrophy than does distance work.The heart does work by pumping blood. The useful mechanical work (external work) done by any pump is equal to the pressure generated by the pump, multiplied by the volume of fluid that is pumped in one pump stroke, multiplied by the number of pump strokes. Therefore the external work done by the left ventricle in 1 minute is equal to the pressure generated, multiplied by the stroke volume, multiplied by the heart rate. The pressure generated by the left ventricle can be approximated by the average (mean) pressure in the aorta, as follows:
.λ∙ λ. e. 1λ λ.. Mean aortic pressure ? Stroke Minute work of left ventricle =. i,
volume ? Heart rate
The external work done by the ventricle in one cardiac cycle is called the stroke work, as follows:
Stroke volume of left ventricle = Mean aortic p,ressure ? ?troke volume
(The work of the right ventricle can be calculated in a similar way, but using mean pulmonary artery pressure.)
In accordance with the analogy to skeletal muscle conditioning, the average aortic pressure is analogous to the force developed by the contracting skeletal muscle; the stroke volume is analogous to the distance moved during one contraction; and the heart rate is analogous to the number of contractions. Obviously, the external work done by the left ventricle could be increased by increasing the pressure that the left ventricle generates, by increasing the stroke volume, or by increasing the heart rate. For example, a 50% increase in ventricular work can result from a 50% increase in the left ventricular pressure, a 50% increase in the left ventricular stroke volume, or a 50% increase in the heart rate. Any of these changes results, over a period of weeks, in left ventricular hypertrophy. However, an increase in the ventricular pressure causes a much more pronounced hypertrophy than does an increase in the stroke volume or heart rate.
The basis for this difference is that increasing the pressure involves the generation of much more internal work (wasted work), which appears as heat. This large expenditure of energy' on internal work greatly increases the total work (external work plus internal work) being done by cardiac muscle. It is the total work of the cardiac muscle, not just the external work, that is the primary stimulus for hypertrophy.Under normal conditions, about 85% of the metabolic energy consumed by the heart appears as heat, and only 15% appears as external work. A physicist would say that the heart has a “thermodynamic efficiency” of about 15%. However, the “cardiac efficiency” depends on the type of work being done by the ventricles. The heart becomes less efficient when the external work is increased by increasing the pressure. Conversely, the heart becomes more efficient when the external work is increased by an increase in the volume of blood pumped.
The dominant role of pressure in determining total ventricular energy consumption is evident from a comparison of the work done by the left and right ventricles. The stroke volume and heart rate are equivalent for the left and right ventricles, but the pressure generated is about five times higher in the left ventricle than in the right (mean aortic pressure is about five times higher than mean pulmonary artery pressure). Therefore the external work done by the left ventricle is approximately five times greater than the external work done by the right ventricle. However, the total metabolic energy consumption of the left ventricle is much more than five times greater than the energy consumption of the right ventricle, because the extra external work performed by the left ventricle is in the form of greater pressure. As a result, almost all the energy consumed by the heart is consumed by the left ventricle. Therefore, almost all the coronary blood flow is delivered to the left ventricular muscle, and almost all the oxygen consumed by the heart is consumed by the left ventricle.
Because of the high amount of pressure work done by the left ventricle compared with the right ventricle, the left ventricle develops much heavier and thicker muscle walls than the right ventricle.A clinical observation from human medicine provides a further illustration of how an increase in the ventricular pressure work leads to ventricular hypertrophy. About 20% of adult humans have hypertension. In most of these patients, cardiac output is normal. Their arterial blood pressure is elevated because of an increased resistance to blood flow in the systemic arterioles. An elevated left ventricular pressure is required to force the cardiac output through these constricted systemic arterioles. The increased pressure work done by the left ventricle in hypertensive patients results in a striking left ventricular hypertrophy.
Up to a point, ventricular hypertrophy is an appropriate and beneficial adaptation to an increased workload imposed on the ventricular muscle. However, excessive hypertrophy is deleterious for three reasons. First, enlargement of the ventricular muscle restricts the opening of the aortic or pulmonic valve. ∕∖ vicious cycle develops. Ventricular hypertrophy leads to aortic or pulmonic stenosis, which necessitates that the ventricle generate an even greater systolic pressure to eject blood, which leads to more ventricular hypertrophy, and so on. A second complication of excessive hypertrophy is that the coronary circulation may be unable to provide enough blood flow to meet the increased metabolic demand of the massive ventricular muscle, particularly during exercise. Inadequate coronary blood flow is especially likely if the coronary vessels have become constricted because of coronary artery disease (atherosclerosis). As a result, patients with ventricular hypertrophy and coronary artery disease are at high risk for cardiac ischemia, myocardial infarction, ventricular arrhythmias, and sudden death during periods of exercise. This explains why the all- too-common combination of hypertension and coronary artery disease is such a serious problem in human medicine. Fortunately, coronary artery disease is rare in most animals. The third complication of cardiac hypertrophy is that the cellular growth factors that mediate the hypertrophy also predispose the cardiac muscle to apoptosis.