Short-Term and Long-Term Responses to Reduced Cardiac Output

2 November, 2011 (06:57) | Heart Diseases | By: Health news

Complex responses of the vasculature, along with remarkable plasticity in the cellular composition of the heart, allow the circulation to adapt to both acute and chronic low-output states. However, the short-term and long-term responses to a fall in cardiac output are quite different. In evolutionary terms, the most important of these responses favor survival after hemorrhage, which is, of course, a short-term challenge to the circulation. This is readily understood, because an ability to recover from an acute blood loss favors the retention in the gene pool of the traits needed to withstand such important causes of hemorrhage as childbirth and the injuries common in those who have the aggressiveness needed to search for food and defend the family. Although essential in meeting these short-term challenges, the responses of the cardiovascular system to low cardiac output can, when sustained, have detrimental long-term effects.

The inotropic response to these second messengers, along with the chronotropic response (not shown), increases cardiac output; however, an increase in the cytosolic calcium concentration may overload the systems that pump calcium out of the cell during diastole and so may also exacerbate the relaxation abnormalities in the failing heart. Cellular calcium overload can also cause transient depolarizations16 that may contribute to the arrhythmias seen in patients with heart failure. Although sympathetic stimulation accelerates the rate of calcium uptake by the sarcoplasmic reticulum, thus promoting relaxation (lusitropy), other abnormalities in the chronically overloaded failing heart depress the rate of calcium uptake (see the next section). Thus, the neurohumoral response to an acute fall in cardiac output initiates adaptive short-term compensatory responses, but when the low-output state becomes chronic, neurohumoral stimulation can have deleterious long-term effects on the heart.
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Depressed Contractility in the Failing Heart

Evidence that contractility is usually depressed in the hypertrophied, failing heart led to the logical corollary that an increase in myocardial contractility would benefit patients with heart failure. Much as the pneumococcus represents the pathogenic organism in lobar pneumonia, depressed contractility was once viewed as the cause of most cases of heart failure. Thus, just as penicillin is the usual treatment for pneumococcal pneumonia, positive inotropic drugs came to be viewed as the specific treatment for heart failure.

The identification of calcium as the key intracellular messenger in cardiac excitation–contraction coupling made possible the development of powerful inotropic drugs. By modifying the myocardial metabolism of calcium, such drugs could alleviate the depressed myocardial contractility then viewed as the chief cardiac abnormality in patients with heart failure. It is possible, however, that powerful inotropic stimulation, although a logical short-term measure to maintain circulatory function in patients with acute heart failure, could have deleterious effects in some patients with chronic congestive heart failure. These effects include cell damage caused by increased energy expenditure, a view that is supported by reports of depressed concentrations of high-energy phosphates in both experimental and clinical heart failure. Since relaxation, like contraction, requires the expenditure of high-energy phosphates, an imbalance between energy production and energy use in the overloaded heart may contribute to the relaxation abnormalities now recognized to have a major pathophysiologic role in heart failure. Inotropic drugs, by increasing cytosolic calcium and cyclic AMP concentrations in the myocardium, may also have arrhythmogenic side effects.