Compensatory heart failure

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. 

TABLE 3-2. Beneficial and Detrimental Effects of the Compensatory Responses in Heart Failure... 

Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

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... 

Some compensatory responses that occur during congestive heart failure. In addition to the effects shown, sympathetic discharge facilitates renin release, and angiotensin II increases norepinephrine release by sympathetic nerve endings (dashed arrows). 

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). 

Hydralazine may cause a dose-related, reversible lupus-like syndrome, which is more common in slow acetylators. Lupus-like reactions can usually be avoided by using total daily doses of less than 200 mg. Other hydralazine side effects include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it may be useful in patients with severe chronic kidney disease and in kidney failure. Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

Hydralazine now has little use long-term for hypertension, but it may have a role as a vasodilator (plus nitrates) in heart failure. It reduces peripheral resistance by directly relaxing arterioles, with negligible effect on veins. In common with all potent arterial vasodilators, its hypotensive action is accompanied by a compensatory baroreceptor-mediated sjmpathetic discharge, causing tachycardia and increased cardiac output. There is also renin release with secondary salt and water retention,... 

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. 

Because a major compensatory response in heart failure is sodium and water retention, restriction of fluid intake and dietary sodium is an important nonpharmacologic intervention. Fluid intake... 

Heart failure is due to defects in cardiac contractility (the vigor of heart muscle), leading to inadequate cardiac output. Signs and symptoms include decreased exercise tolerance and muscle fatigue, coupled with the results of compensatory responses (neural and humoral) evoked by decreases in mean BP. Increased SANS activity leads to tachycardia, increased arteriolar tone T afterload, 4- output, 4 renal perfusion), and increased venous tone (T preload, T fiber stretch). Activation of the renin-angiotensin system results in edema, dyspnea, and pulmonary congestion. Intrinsic compensation results in myocardial hypertrophy. These effects are summarized in Figure IH-4-1. 

The increase in contractility improves cardiac output, reversing the compensatory tachycardia and the increases in BP and TPR that occur in heart failure. Renal perfusion and diuresis are also improved, providing additional beneficial effects in heart failure. However, cardiac glycosides do not improve survival thus, ACEIs are now considered drugs of first choice in most situations. 

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