Historical Treatments

The earliest measures for treating dropsy were chiefly attempts to correct humoral imbalances. Cel-sus, for example, recommended drugs he regarded as diuretics, as well as a wide variety of other medicines with different physiological effects. (One of his diuretics, squill, was finally abandoned only after White demonstrated its lack of dependability in 1920.) During the Renaissance, Capivaccio, Mercatus, and Piso were still recommending Galenic drugs to carry away dropsical fluid, especially cathartics, emetics, diaphoretics, expectorants, and diuretics like squill. In addition, Capivaccio pointed out that blistering with cantharides ("Spanish flies") and paracentesis would remove dropsical fluid, but he recommended bleeding only if the patient's blood had been diseased because of disturbed liver function.

The number of drugs recommended for dropsy diminished during the course of the seventeenth century. The Leopoldine Academicians described some they thought would increase blood viscosity by removing excess fluid from the body, such as diuretics, cathartics, and diaphoretics. Baglivi and Lancisi favored diuretics almost exclusively. Malpighi and his student, Albertini, on the other hand, who based their treatments on the teachings of Hoffmann, recommended tonic drugs to strengthen the tone of the weakened resorbing veins, so that fluid that had leaked into the tissues could be removed more readily. So did Clossey and Monro, who said that dropsy should be treated with tonic drugs, "which by their stimulus force the sensible [i.e., excitable] organs into contractions."

In 1785, there appeared the single most influential-and perhaps most widely read and immediately accepted - book in the history of dropsy, An Account of the Foxglove, by William Withering of Birmingham, England. His was the first prospective study of the clinical efficacy and safety of any drug, for the treatment of any disease. Using historical controls as negative controls, Withering clearly demonstrated the therapeutic benefit of digitalis in patients with dropsies that were not related to primary disease in other organs, such as the ovaries. Because increased urine production usually followed the administration of digitalis, he thought it was a diuretic. Although he noted that the pulse rate fell in patients whose symptoms were ameliorated by the new drug, he did not recognize the drug's tonic effect on the heart.

Because dropsy had been seen since the mid-eighteenth century as a "weakness and laxity of the fibers," some physicians who followed Withering concluded that digitalis stimulated the "system," whereas others concluded that it was a depressant because it reduced fast heart rates. In 1813 Blackall (not John Ferriar, as some have supposed) first suggested that digitalis actually strengthens the heart. This concept resurfaced in papers published in 1905-11 by James Mackenzie of London and Karel Frederik Wenckebach of Holland and Vienna, but it was only verified in 1938-44, by H. J. Stewart and John McMichael. Wenckebach also demonstrated the efficacy of digitalis in atrial fibrillation.

The two major clinical goals of treatment in congestive heart failure today are improved oxygenation of the tissues by increasing cardiac output, and reduction of hydrostatic pressures in the veins. Digitalis glycosides (chiefly digoxin and digitoxin, both of which must still be extracted from the purple foxglove, Digitalis purpurea, or the white species, Digitalis lanata) increase cardiac output by strengthening the force with which the heart contracts; diuresis occurs secondarily, because the resulting increase in the amount of blood that can then be circulated to the kidneys permits increased removal of water into the urine. True diuretics, which act on the kidneys alone, relieve pressure in the venous system by removing excess fluid from the body via the urine.

Other drugs now used in the treatment of heart failure include dopamine, dobutamine, hydralazine, nitroprusside, and enalapril; although all of these agents reduce hydrostatic pressures by dilating blood vessels, they act on the vessels in different ways. Enalapril is unusual in that it can also facilitate reversal of left ventricular hypertrophy. In addition, amrinone and milrinone both dilate vessels and increase the force of cardiac contraction. Oxygen and rest, which may have to be induced with sedatives, are important adjuncts to drug therapy. Paracentesis and thoracentesis may occasionally still be required, but the subcutaneous leg drainage tubes described by R. Southey of London in 1871 were abandoned with the advent of true diuretics. Patients with acute pulmonary edema (as in acute cor pulmonale) are often treated with morphine, which reduces not only their anxiety and their tachycardia but also their hydrostatic pressures against blood flow (via an effect in the central nervous system).

J. Worth Estes

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