Heart failure compensatory mechanisms

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

Heart rate The heart rate is a major determinant of cardiac output. As the intrinsic function of the heart decreases in failure and stroke volume diminishes, an increase in heart rate—through sympathetic activation of adrenoceptors—is the first compensatory mechanism that comes into play to maintain cardiac output. 

A compensatory mechanism is initiated in the event of congestive heart failure. This consists of ... 

Cardiac glycosides bring about diuresis by increasing both cardiac output and renal blood flow the latter in turn reverses the renal compensatory mechanism activated in congestive heart failure. Consequently, the production of aldosterone is reduced, sodium retention is reversed, and the excretion of edematous fluid is enhanced (Figure 35.5). 

It is well established that increased sympathetic nerve activity is associated with chronic heart failure (CHF) (Porter et al. 1990 Singh 2000 Olshansky 2005 Brodde et al. 2006 Watson et al. 2006). The increase in sympathetic activity is a compensatory mechanism that provides inotropic support to the heart and peripheral vasoconstriction. However, it promotes disease progression and worsens prognosis (Watson et al. 2006). The autonomic nervous system (ANS) is a very complex, balanced system that influences the initiation, termination, and perpetuation of atrial fibrillation (AF), and the AF affects the ANS (Olshansky, 2005). At rest, sympathetic and parasympathetic outflows are related reciprocally heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows (Porter et al. 1990). 

The decreased ability of the failing heart to sustain adequate cardiac output causes the kidney to respond as if there were a decrease in blood volume. The kidney, as part of the normal compensatory mechanism, retains more salt and water as a means of raising blood volume and increasing the amount of blood that is returned to the heart. However, the diseased heart cannot increase its output, and the increased vascular volume results in edema (see p. 151 for causes and treatment of congestive heart failure). 

Furosemide is a widely used loop diuretic indicated for the treatment of different pathological conditions such as congestive heart failure, hepatic cirrhosis, and chronic renal failure. It has a narrow absorption window and mainly absorbed from the stomach and the upper part of the small intestine. Following administration of furosemide, the natriuretic effect rapidly disperses and is concealed before the next administration. This problematic aspect in furosemide therapy is mostly attributed to the natural homeostatic compensatory mechanisms. Lately, it has been demonstrated that the diuretic and natriuretic effects of furosemide can be significantly improved, following a continuous input (intravenous infusion) compared to immediate release DFs. Beside the narrow absorption window, this pharmacodynamic feature of the drug provides another rationale for the development of a GRDF for furosemide. 

Heart failure is a progressive disorder that begins with myo- cardial injury. In response to the injury, a number of compensatory responses are activated in an attempt to maintain adequate cardiac output, including the sympathetic nervous system, increased preload, vasoconstriction, and ventricular hypertrophy/remodeling. These compensatory mechanisms are responsible for the symptoms of heart failure and contribute to disease progression. 

Ventricular function (Frank-Starling) curves, which plot any function of preload versus any function of cardiac work, reveal that compensatory mechanisms in untreated heart failure (mostly deleterious) may shift such curves upward and to the left. Compensation in heart failure is offset by specific drugs that can ... 

Heart failure results in edema either because of increased hydrostatic pressure in capillaries or because of a compensatory renal mechanism. As the effective output of the heart decreases, renal flow, and therefore glomerular filtration, also decrease. Reabsorption of sodium and water is more complete, resulting in increased tissue retention of both substances. Digitalis has a diuretic effect to the extent that it relieves the underlying factors in the heart. 

Patients with compensated heart failure often have increased sympathetic nervous activity as a compensatory mechanism. Propranolol can precipitate acute exacerbation of CHF in such patients. 

Compensatory mechanisms in heart failure tend to increase the heart rate, further diminish-... 

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