Both Starling’s Mechanism and the Arterial Baroreflex Help Compensate for Heart Failure

There are many types and causes of heart failure. Some clinicians use the term very broadly to refer to any condition in which a problem in the heart limits its ability to deliver a normal cardiac output to the body tissues. Such conditions would include various valve defects, arrhythmias, and even heartworm infestation. A more restrictive definition, and one favored by physiologists, is that heart failure is any condition in which a depressed cardiac contractility limits the ability of the heart to deliver a normal cardiac output. The broader definition of heart failure encompasses virtually any problem with the heart as a pump; a common synonym is pump failure. The more restrictive definition, as used in this chapter, equates heart failure with myocardial failure, a depressed contractility of the heart muscle itself.

A depressed cardiac contractility can result from coronary artery disease, cardiac hypoxia, myocarditis, toxins, drug effects, or electrolyte imbalances. If the decrease in contractility affects both sides of the heart, the condition is called bilateral heart failure. In other circumstances, failure may be restricted primarily to either the left ventricle or the right ventricle and thus is called left-sided heart failure or right-sided heart failure.

Ventricular function curves provide a helpful way to envision the consequences of heart failure and the compensations for heart failure. In Figure 26-1 the curve labeled Normal indicates the relationship between stroke volume and preload for a normal ventricle (for a review, see Figure 21-3, C). The curve labeled Initially severe failure shows that a ventricle in failure has a depressed contractility (i.e., a smaller stroke volume for any given preload). If a normal heart suddenly goes into severe failure, stroke volume changes from its normal value (shown by point 1) to the low value (shown by point 2). For purposes of illustration, imagine that these curves define the function of the left ventricle and that the left ventricle is the one that fails. A decrease in left ventricular stroke volume causes a decrease in left ventricular output, which results in a decrease in mean arterial blood pressure. If there is inadequate compensation for this fall in blood pressure, severe exercise intolerance is certain, inadequate perfusion of the critical organs is likely, and death is a strong possibility. However, several mechanisms react rapidly, within seconds to minutes, to compensate for heart failure and to minimize its adverse effects.

One compensation for heart failure is Starling’s mechanism. If the left ventricle suddenly decreases its stroke volume, the right ventricle (at least for a few heartbeats) maintains a higher stroke volume than the failing left ventricle. The excess blood pumped by the right ventricle has to “go somewhere,” and most of the excess accumulates in the pulmonary veins and left atrium. In effect, blood backs up or dams up behind (i.e., upstream of) the left ventricle. The resulting increase in left atrial pressure creates an increase in left ventricular preload, which leads to an increase in left ventricular end-diastolic volume and, by Starling’s mechanism, an increase in stroke volume. This improvement in stroke volume is depicted in Figure 26-1 as a transition from point 2 to point 3. The sequence of events, whereby an increase in preload helps offset the initial fall in stroke volume, is also diagrammed in Figure 26-2 (top left loop). Note that the compensation by Starling’s mechanism does not return stroke volume to its normal value because contractility remains severely depressed; however, without this compensation severe heart failure would be fatal.

The arterial baroreflex is another mechanism that reacts rapidly to compensate for heart failure. Even after compensation by Starling’s mechanism, left ventricular output remains below normal, as does arterial blood pressure. Therefore, baroreceptor activity is below normal. The central nervous system (CNS) responds reflexively by increasing sympathetic efferent activity to the heart and blood vessels and by decreasing parasympathetic activity to the heart.

The sympathetic effect on the heart increases ventricular contractility. Contractility is not restored to normal but is brought to a higher level than existed in the absence of reflex compensation. Graphically, the effect of the baroreflex is to move the failing ventricle to a function curve that is intermediate between the Normal curve and the curve of Initially severe failure (see point 4 in Figure 26-1). Note that the increase in contractility also brings stroke volume back toward (but not reaching) its normal level.

The reflexive increase in sympathetic activity raises heart rate above normal and decreases systolic duration; these changes also help to restore cardiac output and arterial pressure toward normal despite the persistently depressed stroke volume. Finally, sympathetic activation causes vasoconstriction, particularly in the noncritical organs, which increases total peripheral resistance (TPR) above normal. This also helps to return arterial pressure toward its normal level.

The net effect of the compensations by way of Starling’s mechanism and the baroreflex is that arterial blood pressure can be maintained near its normal level, at least when the animal is at rest, despite a severe ventricular failure. Figure 26-2 summarizes these reflex effects. Note that after compensation by Starling’s mechanism and the baroreflex, contractility, stroke volume, cardiac output, and blood pressure remain at least somewhat below normal. By contrast, preload, sympathetic activity, heart rate, and TPR are above normal.

Serious Complications Secondary to Heart Failure Include Exercise Intolerance, Edema, Salt and Water Retention, Kidney Failure, Uremia, Septic Shock, and Decompensation

Even though Starling’s mechanism and the baroreflex can compensate to a remarkable degree for severe heart failure, important secondary complications often develop. These complications make heart failure a serious clinical problem, even in cases where compensatory mechanisms can maintain cardiac output and arterial pressure at near-normal levels when the animal is at rest.

Heart failure causes exercise intolerance. In a normal animal the ability of the heart to increase cardiac output during exercise depends on sympathetically mediated increases in stroke volume and heart rate. In a patient with heart failure, however, sympathetic activation is being harnessed to restore cardiac output toward normal in the resting state. Therefore the patient has a limited ability to invoke an effective, further increase in sympathetic activity. The failing heart cannot provide the increased cardiac output required to meet the blood flow requirements of exercising skeletal muscle. In the absence of an adequate increase in cardiac output, metabolic vasodilation in the exercising muscle results in a large decrease in arterial pressure and inadequate blood flow to all organs, including the exercising muscle. The patient exhibits lethargy and weakness; even mild exercise leads quickly to exhaustion.

Edema is another serious complication secondary to heart failure. As noted, blood dams up in the atrium and veins behind a failing ventricle. In the case of left ventricular failure, left atrial pressure increases, as does pressure in the pulmonary veins and pulmonary capillaries. The increase in pulmonary capillary hydrostatic pressure leads to an increase in the filtration of capillary fluid into the interstitial spaces of the lungs. Pulmonary edema develops. The excess of interstitial fluid slows the transfer of oxygen from the lung alveoli into the lung capillaries and can result in inadequate oxygenation of the blood (hypoxemia). In extreme cases, interstitial fluid leaks into the intrapleural space (pleural effusion) or into the alveolar air spaces, which causes a further reduction in lung function. The resulting hypoxia in critical organs can be fatal. In a patient with right ventricular failure the increase in venous pressure occurs in the systemic circulation. Therefore the resulting edema occurs in the systemic organs, particularly in dependent extremities and in the abdomen. The cause-and-effect sequence by which heart failure leads to edema is summarized in Figure 26-3 (top left).

Whether the edema is in the lungs or in the systemic circulation, its degree is limited by the three safety factors previously discussed (see Figure 23-5). These safety factors would probably keep the edema of heart failure well controlled were it not for an additional factor that exaggerates the elevation of venous pressure in heart failure. As long as arterial pressure remains subnormal in a patient with heart failure, the baroreceptor reflex and some mechanisms involving the kidneys work to raise blood volume above normal. These volume-increasing mechanisms include increased thirst (which raises fluid intake), increased release of antidiuretic hormone (ADH) from the pituitary (which decreases the amount of fluid lost in the urine), and activation of the renin-angiotensin-aldosterone system (which decreases sodium loss in the urine). These effects of the baroreflex were mentioned briefly in Chapter 25; the mechanisms involving the kidneys are described in more detail in Chapters 41 and 43.

The point for now is that the patient with severe heart failure experiences a substantial and persistent increase in blood volume. The excess blood accumulates particularly in the veins upstream from the failing ventricle, which exaggerates the increases in venous pressure and capillary filtration. The normal safety factors against may be overwhelmed. This is why one of the main goals in the clinical treatment of heart failure is to counteract the buildup of excessive blood volume and interstitial fluid volume. Diuretic drugs are the main therapies used for this purpose (see Chapter 43).

Severe, persistent heart failure leads to several additional adverse effects. The baroreceptor reflex responds to an abnormally low arterial pressure in heart failure by initiating arteriolar vasoconstriction, primarily in the kidneys, splanchnic organs, and resting skeletal muscle (the noncritical organs). In severe heart failure the skin and mucous membranes are also vasoconstricted. Vasoconstriction in these organs helps compensate for heart failure by permitting the available cardiac output to be routed to the critical organs (brain, heart, and working skeletal muscle). However, persistent vasoconstriction leads to the additional complications of kidney failure, uremia, and septic shock.

Vasoconstricted kidneys cannot form urine in a normal manner and therefore do not rid the body of the excess volume of blood and interstitial fluid that accumulates in heart failure. Persistent vasoconstriction damages kidney tissue and leads to a buildup of nitrogenous and acidic waste products in the body. The condition is called uremia, which literally means “urine in the blood.” To make matters worse, after a prolonged period of intense vasoconstriction, damage to the kidney tissue becomes irreversible. At this stage, uremia, acidosis, and salt and water retention may persist even if clinical treatment is temporarily successful in returning cardiac output and blood pressure close to normal. For this reason, renal failure often is the terminal event in chronic heart failure.

Intense and prolonged vasoconstriction in the splanchnic circulation can also have lethal consequences. The mucosa of the gastrointestinal tract is particularly susceptible to ischemic damage. Normally, the intestinal mucosa creates a barrier between the contents of the intestinal lumen and the bloodstream. Ischemic damage to the intestinal mucosa allows bacteria and bacterial toxins to pass into the bloodstream or the peritoneum. The resulting bacteremia or peritonitis can cause septic shock and death. The causes and consequences of renal and splanchnic ischemia are summarized in Figure 26-3 (bottom right).

Cardiac decompensation is an additional (and frequently terminal) complication secondary to heart failure. The basic concept of decompensation is that when heart failure reaches a certain degree of severity, the body’s attempted compensations for heart failure end up making the heart failure worse. Vicious decompensatory cycles develop and can lead to death within a few hours unless there is vigorous medical intervention.

The specific mechanisms of the decompensatory cycles are very complex, but three examples illustrate the concept. As previously explained, in the case of left ventricular failure, the damming up of blood in the left atrium is compensatory because it increases left ventricular preload, which helps boost stroke volume back toward normal. However, the increased left ventricular preload leads to the secondary complication of pulmonary edema. If severe, pulmonary edema interferes with the oxygenation of blood. One tissue that depends critically on an adequate supply of oxygen is cardiac muscle; hypoxia depresses the contractility of cardiac muscle. Thus a vicious cycle can develop: severely depressed ventricular contractility → severe pulmonary edema → inadequate oxygenation of blood → hypoxia of the left ventricular muscle → further depression of ventricular contractility.

For a second example of a vicious decompensatory cycle, consider again the effects of the baroreflex on the kidneys. Renal vasoconstriction is compensatory for heart failure in that it helps increase TPR, which helps raise arterial pressure back toward normal, which helps keep perfusion pressure high enough to deliver adequate blood flow to the critical organs. However, as already mentioned, intense and prolonged renal vasoconstriction leads to kidney failure and an accumulation of acidic and nitrogenous waste products in the blood (uremia). Uremia depresses cardiac contractility. Thus, another vicious cycle can develop: severe ventricular failure → intense and prolonged renal vasoconstriction → damage to kidney tissues → uremia → metabolic waste products accumulate in cardiac muscle → further depression of ventricular contractility.

A third vicious decompensatory cycle results from the fact that septic shock depresses cardiac contractility. The cycle is: severe ventricular failure → intense and prolonged splanchnic vasoconstriction → ischemic damage to intestinal mucosa → bacteria and endotoxins pass through the damaged mucosa, from intestines into bloodstream → bacteremia causes further depression of ventricular contractility.

Other decompensatory cycles develop in cases of severe, prolonged heart failure, but these three examples (which are illustrated in Figure 26-3) show why decompensation is such a serious development.

Careful clinical diagnosis and prompt treatment of heart failure are imperative, even if compensatory mechanisms have maintained blood pressure near its normal level when the patient is at rest. In evaluating the severity of heart failure and the extent of compensation, it is clinically useful to group the signs of heart failure into two categories. The first category is referred to as backward heart failure. The signs of backward heart failure include the changes in the circulation upstream from the failing ventricle: increased atrial pressure, increased venous pressure, excessive capillary filtration, edema, and the functional changes secondary to edema (e.g., respiratory failure). The category forward heart failure refers to the consequences of heart failure downstream from the failing ventricle: decreased cardiac output, decreased arterial blood pressure, and the consequences of excessive vasoconstriction in the systemic organs, especially the kidneys and intestines.

The Immediate Cardiovascular Effects of Hemorrhage Are Minimized by Compensations Initiated by the Atrial Volume Receptor Reflex and the Arterial Baroreceptor Reflex

Figures 26-4 and 26-5 summarize the cardiovascular responses to hemorrhage. The curve labeled Normal in Figure 26-4 shows that the maintenance of a normal stroke volume depends on the maintenance of a normal level of ventricular preload. When hemorrhage occurs, blood is lost from the whole cardiovascular system, but particularly from the veins, which are the blood reservoirs of the body. Hemorrhage therefore decreases venous volume, venous pressure, atrial pressure, ventricular preload, and ventricular end-diastolic ventricular volume. In the absence of any compensation, ventricular stroke volume decreases from point 1 in Figure 26-4 to point 2.