39 Dropsy

The historical diagnosis of dropsy-which is now obsolete - indicated simply an abnormal accumula­tion of fluid; the word derives from the Greek hy­drops (water). Alternative or supplementary terms included hydrothorax (fluid in the chest cavity), ascites (which still indicates excess free fluid in the abdominal cavity), anasarca (still used to describe generalized edema throughout the body), hydro­cephalus (used until the nineteenth century to indi­cate excess fluid within the skull), and ovarian dropsy (large ovarian cysts filled with fluid).

Etiology and Epidemiology

The major underlying causes of dropsy are conges­tive heart failure, liver failure, kidney failure, and malnutrition. Because they were not clearly differen­tiated before the nineteenth century, a historical diagnosis of dropsy cannot be taken to indicate any one of these alone in the absence of unequivocal supporting evidence, as from an autopsy. However, heart failure was probably the most frequent of the four.

The etiologies of dropsy can be explained most con­veniently in terms of fluid balance. One principal force in the maintenance of normal fluid balance is the hydrostatic (or hydraulic) pressure within capil­laries. The other major force is oncotic pressure, the normal tendency for sodium or large particles (e.g., proteins) in capillary blood to draw water out of tis­sues, much as salt draws water to the cut surface of a raw potato. Thus, fluid accumulates in tissues when either intracapillary pressure increases or the blood’s ability to remove water from tissues decreases.

Congestive heart failure produces dropsy, or edema, when the heart becomes too weak to maintain the normal pressure head behind blood flow in the capil­laries, so that even the normal resistance to flow through them facilitates the leakage of water from capillary blood into surrounding tissues. The adjec­tive “congestive” refers to the accumulation and stagnation - congestion — of blood in organs, espe­cially the lungs, when they are not adequately emp­tied because of backward pressure from obstructions distal to them.

The other major causes of dropsy, which appear chiefly as edema of the foot (pedal edema) and ankle, ascites, and occasionally anasarca, are listed below for the sake of completeness, but will be discussed further only in relation to heart failure:

1. Liver failure capable of producing ascites most often occurs in advanced cirrhosis because the diseased liver cannot manufacture sufficient pro­tein (albumin) to maintain the oncotic pressure of the blood. Right ventricular failure (see below) can also produce hepatic congestion and failure.

2. Renal failure causes dropsy when the glomerular filtering units become so diseased (e.g., in glomerulonephritis, first known as Bright’s dis­ease) that albumin and other large molecules are lost from the blood into the urine, resulting in decreased oncotic pressure.

3. Malnutrition results in ascites when protein in­take is so low that the liver is unable to manufac­ture adequate amounts of albumin. Beriberi, the result of insufficient dietary thiamine, can also weaken the heart.

The epidemiology of dropsy is that of its underly­ing causes. For instance, elevated serum cholesterol levels and smoking both predispose to hypertension and myocardial infarction (“heart attack”), which are major causes of heart failure.

However, the epidemiology of some forms of dropsy has changed in recent years. The introduc­tion of penicillin for the treatment of streptococcal infections after World War II, for example, has re­duced the occurrence of their cardiac and renal se­quelae. On the other hand, the increasing life expec­tancy of Americans in the twentieth century for many years meant an increased incidence of heart disease. Now, however, recent data suggest that the incidence of coronary artery disease and myocardial infarction has been falling, perhaps as a result of factors such as changes in diet and exercise level.

Heart failure occurs more often in men than women, inasmuch as men are at greater risk for most forms of cardiovascular disease. The risk is greater for older than younger patients: Three quar­ters of heart failure patients are over 50 years of age. Risk factors for hepatic cirrhosis include chronic alco­holism and hepatitis, just as renal causes of dropsy may be associated with rheumatic fever or the nephrotic syndrome.

Distribution and Incidence

The distribution of dropsy within or among popula­tions parallels the distributions of its underlying causes, such as hypertension, myocardial and coro­nary artery insufficiency, hypercholesterolemia, val­vular disease, streptococcal infection, cirrhosis, and renal glomerular disease. Risk factors for these con­ditions are still being identified and their clinical implications evaluated. Only for malnutrition are geographic distinctions clear-cut (e.g., in drought- stricken areas of Africa, or countries where diet cen­ters too closely on polished rice).

Historically, a diagnosis of dropsy was based sim­ply on abnormal accumulations of fluid in the legs, abdomen, or chest.

Framingham (Mass.) Heart Study in 1971. In 1985,3 of every 1,000 Americans were reported to develop heart failure annually, producing an overall inci­dence of about 1 percent of the population, regardless of age; 34 to 58 percent of heart failure patients die each year.

Clinical Manifestations and Pathology

This discussion focuses only on congestive heart fail­ure because it was probably the major underlying cause of dropsy. The heart is able to compensate, up to a point, for diminished strength of contraction, for increased resistance to arterial outflow (resulting in “pressure overload”), and for accumulations of blood that cannot be completely removed from the ventri­cles at each contraction (resulting in “volume over­load”). The usual responses to these stresses include the following: (1) reflexly increased heart rate (tachycardia), to speed blood flow (actually, oxygen delivery) into the arteries; (2) hypertrophy (in­creased mass) of ventricular muscle, in response to pressure overloads; and (3) dilation and thinning of ventricular walls, in response to volume overloads, although hypertrophy can be expected to follow as a further adjustment.

Symptoms of heart failure begin to occur when no further compensations can be made. “Forward fail­ure” symptoms occur when the heart can no longer empty the left ventricle completely because of rea­sons such as myocardial weakness or obstruction to aortic outflow. Normally the ventricles eject 60 to 66 percent of the blood in them at each beat. But when only 40 percent of the blood in the left ventricle can be expelled, symptoms begin to appear, and they become severe when only 20 percent can be expelled. Symptoms of “backward failure” occur when the heart chambers become incapable of complete fill­ing, due to incomplete relaxation of the heart be­tween beats, or to obstructions to venous inflow into the right atrium.

Heart failure can be produced by several underly­ing pathological causes, although seldom does any one of them occur alone:

1. Myocardial insufficiency, in which the heart is too weak to maintain normal blood flow, occurs acutely when a substantial portion of the muscle is incapacitated by infarction, or in association with gradual left ventricular failure. Both dila­tion and hypertrophy are likely adaptations.

2. Left ventricular failure may occur suddenly, after a myocardial infarction, or slowly, owing to pres­sure overload, most often imposed by increasing resistance (hypertension) to blood expelled into the aorta. Other causes include stenosis (narrow­ing) of the aortic valve, which increases the pres­sure against which the heart must pump, and aortic insufficiency, also called regurgitation, which occurs when an incompetent valve that can­not close permits a volume overload to build up as blood flows back into the left ventricle instead of forward into the aorta.

3. Right Ventricularfailure usually follows when the pressure head built up as a result of left ventricu­lar failure is transmitted backward through the pulmonary vessels to the right ventricle. Other causes of right heart failure include stenosis of the mitral valve, cor pulmonale (see below), and insufficiency of the tricuspid valve.

4. Failure of both ventricles simultaneously usually accompanies a strain common to both sides of the heart, as in constrictive pericarditis, beriberi, hy­pothyroidism, or anemia so severe that the heart rate increases markedly to compensate for the reduced number of red blood cells delivering oxy­gen to the tissue.

5. Chronic cor pulmonale (pulmonary heart disease) occurs when chronic obstructive pulmonary dis­ease (e.g., emphysema) increases resistance to out­flow from the right ventricle, resulting in right ventricular failure.

6. Acute cor pulmonale is caused by sudden massive obstruction of the pulmonary circulation, almost always by a clot that has formed as a result of thrombophlebitis in a leg vein, and has dislodged (embolized) so that it follows the venous pathway to the right heart and thence into the lungs, where it becomes wedged so as to obstruct blood flow distal to it. The results include infarction of the affected lung, impaired venous return, and dilation of the right ventricle.

7. Less frequent causes of congestive heart failure include, among others, diminished arterial blood flow to both kidneys, resulting in decreased so­dium excretion.

Whatever the underlying cause, the major mani­festation of heart failure is reduced cardiac output, measured as the liters of blood ejected from the left ventricle per unit time. The associated symptoms and signs are usually clearly recognizable.

For instance, the first symptoms of left heart fail­ure are those of being quick to tire and having shortness of breath (dyspnea), due to insufficient delivery of oxygen to the body’s tissues, followed by rapid breathing (tachypnea) as the respiratory sys­tem attempts to compensate for the lack of oxygen. Both dyspnea and tachypnea increase as fluid from the pulmonary capillaries begins to flood the lungs. When the lungs become sufficiently congested (pul­monary edema), the patient coughs up copious spu­tum, which is characteristically rust-colored (with small amounts of blood) if mitral stenosis is pres­ent. Stertor (noisy inspirations) often accompanies the dyspnea. A more serious form of dyspnea is orthopnea. This term is applied to shortness of breath that prevents the patient from sleeping hori­zontally because venous blood, which remains in the lower part of the body as a result of gravity during waking hours, further congests the lungs, causing dyspnea. An exaggerated form of orthopnea called paroxysmal nocturnal dyspnea may waken the patient suddenly at night; it is sometimes called “cardiac asthma” because it produces wheezing and labored breathing.

Physical examination and X-rays reveal cardiac enlargement and fluid in the lungs and chest; other tests can confirm that cardiac output is low. Fur­ther symptoms of left heart failure as it worsens include pale dusky skin, sweating, cold hands and feet, and tachycardia, all reflex responses to dimin­ished cardiac output, and decreased urine output (oliguria) secondary to diminished blood flow through the kidneys.

Although right heart failure is far more likely to occur as a sequela of left heart failure than by itself, it does produce distinctive symptoms in addition to the usual dyspnea and tachypnea, both of which may be more pronounced in right than left heart failure. Pedal edema occurs, accompanied by hydrothorax. Ascites is a late sign of right heart failure, and may be followed by anasarca and oliguria. The skin becomes bluish (cyanosis), because the sluggishly moving red cells are not adequately oxygenated in the lungs. The jugular veins in the neck distend because the in­creased pressure in the right heart prevents them from emptying completely into the superior vena cava. Other evidence of increased venous pressure includes congestive enlargement of the liver (hepato­megaly) and sometimes the spleen (splenomegaly).

History and Geography

Dropsy is not much different from one geographic area to the next, except when it accompanies local­ized famines or beriberi induced by local dietary hab­its, and the symptoms of dropsy have not changed over the centuries. Its history is the story of evolving interpretations of its clinical features over 2,000 years as the relationships of dyspnea, “suffocative catarrh,” pulmonary edema, hydrothorax, ascites, syncope, and “fever” to heart failure were elucidated.

Antiquity Through the Fifteenth Century

The first known mention of dropsy is in an Egyptian medical text of about 1550 B.C., the Ebers Papyrus. It associates dropsy with increased abdominal girth, and hints that it is accompanied by a weak pulse. The Hippocratic Aphorism VII, 47, correctly prognos­ticates that “[t]here is no hope when a patient suffer­ing from dropsy develops a cough.” And Jesus defied the lawyers and Pharisees by healing a man with dropsy on the Sabbath (Luke 14), although no symp­toms are recounted. Soon after, Aulus Cornelius Celsus described two forms of dropsy: (1) generalized edema (aqua inter cutem), which could be drained through small skin incisions above the ankle; and (2) ascites, in which the excess fluid detectable by observing fluid waves in the abdominal wall could be removed by paracentesis, or tapping (i.e., drain­age through a metal tube inserted through an inci­sion in the abdominal wall).

Galen of Pergamum listed several causes of dropsy in the first century A.D., including a hardened liver, as well as inadequate blood formation (which he thought occurred in the liver), hemorrhoids, and both amenorrhea and uterine hemorrhage. Virtu­ally all writers on dropsy until the mid-seventeenth century cited the teachings of Hippocrates, Celsus, and Galen. Their ideas were also relayed in the eleventh century by Avicenna of Baghdad, who thought that the tachycardia, palpitations, pulmo­nary edema, dyspnea, and syncope (fainting or shock, which he postulated was a sign of a weak heart) that accompanied dropsy were related to one another.

Sixteenth and Seventeenth Century

Five centuries later, the French surgeon Ambroise Pare described dropsy in identical terms. His coun­tryman Jean Fernel relied on the same theories when he associated heart disease, but not dropsy specifically, with palpitations, syncope, and the pal­lor, cold sweat, and weak pulse often observed in cardiogenic shock. Also in the sixteenth century, Paracelsus theorized that dropsy (wassersucht) oc­curred when the body’s tissues dissolved. He associ­ated it with dyspnea, cough, and oliguria. Following his usual mystical chemical reasoning, he recom­mended that dropsy be treated with mercuric oxide to remove superfluous water, with other metallic oxides to dry the patient’s body, and with sulfur, because its drying action was analogous to that of the sun in dispelling rain.

Like his contemporaries, Girolamo Capivaccio of Italy agreed with Galen that dropsy was due to liver disease and impaired blood formation, so that fluid was released into the abdominal cavity to form ascites, which he detected by percussion, as Celsus had. Capivaccio also attributed dropsy to disease in other organs, such as obstruction of the pathways to the kidneys, but he did not mention the heart or even hydrothorax; he surmised that dyspnea was caused by upward pressure from a pathologically enlarged liver on the diaphragm.

The sixteenth-century physician Ludovicus Merca­tus of Valladolid defined dyspnea as rapid, difficult breathing, sometimes accompanied by stertor, caused by constricted airways or by excess heat in the heart and lungs; he thought the chief function of respira­tion was to cool the heart. He followed Galen’s classi­fication of dyspnea into three stages of increasing severity: tachypnea, asthma (by which he meant con­vulsive gasping for breath), and orthopnea. Mercatus thought that hydrothorax fluid descended from the brain to produce the “suffocative catarrh” described by Galen as suffocation in the absence of inflamma­tion, and that its associated dyspnea was caused by fluid in the lungs, or even by heart disease. He theo­rized that hydrothorax fluid was overflow from ascites or from obstructed urinary passages.

Throughout the seventeenth century, it became increasingly clear that dropsy was associated with altered fluid dynamics as postmortem dissections and experimentation were exploited more fre­quently. For instance, Carolus Piso (Charles Ie Pois) of Lorraine detected hydrothorax as “bubbling” when he applied his ear to the chest. Coupling clini­cal observations with autopsy findings, he attrib­uted paroxysmal nocturnal dyspnea to fluid in the chest cavity. Fabrizio Bartoletti of Italy disagreed with Mercatus and Capivaccio in some of their inter­pretations, but he used observations like Piso’s to hypothesize that hydrothorax fluid came from the lungs. He noted that the first clue to its presence was dyspnea on exertion, followed by “fever” (which he probably detected as modest tachycardia), tachyp­nea, orthopnea, dry cough, thirst, syncope, leg and scrotal edema, and, finally, ascites. Bartoletti thought that although hydrothorax was not rare, it was always fatal because it suffocated its victims.

In 1616 William Harvey found that edema accu­mulated behind ligated veins. Later he postulated that if the entire venous system were maximally distended, the heart would stop and suffocation would follow. In De Motu Cordis (1628), he described the heart and lungs as “storehouses” for the blood, the metaphor that Saul Jarcho, the leading student of dropsy, thinks led to the concepts of pulmonary engorgement and passive congestion - concepts that would prove to be critical to further understanding of dropsy in the chest.

In his Tractatus de Corde (1669), Richard Lower of Oxford and London described how he had produced edema and ascites in dogs by ligating the jugular veins and the superior vena cava. He also found that excess fluid in the pericardial sac could restrict car­diac expansion sufficiently to diminish venous re­turn, resulting in bradycardia, syncope, and death. Lower went on to postulate that the right and left sides of the heart should be of equal strength in order to maintain the circulation, while noting that the left side alone may be weakened, an early expres­sion of the notion of forward failure. He also per­ceived that excessive amount, pressure, or flow rate of blood might adversely affect health. Finally, he recognized Galen’s “suffocative catarrh” as pulmo­nary edema, although they were considered to be separate clinical entities for many years afterward.

In 1681 Marcello Malpighi of Bologna carried Har­vey’s quantitative approach to experimental physiol­ogy an important step further when he noted the increased weight of dyspneic lungs (attributable to the stagnant blood within them). Because he had discovered capillaries 20 years earlier, he could hy­pothesize that blood escaped from them into the lungs. Malpighi thought that stagnant blood in the pulmonary vessels produced palpitations and irregu­lar pulses because it precluded an orderly blood sup­ply to the heart. He reasoned that an imbalance between arterial outflow and venous resorption of water from the blood caused dropsy, but he attrib­uted the imbalance to chemicals that constricted blood vessels or irritated and thus stimulated the nerves that controlled the heart and the respiratory muscles. One of Malpighi’s students, Giorgio Bag- livi, described the symptoms of suffocative catarrh so that it finally became clearly recognizable as acute pulmonary edema (not the result of fluid fall­ing from the head): dyspnea, cough, stertor, sensitiv­ity to cold, chest pain, thirst, anxiety, and, one of his major original observations, foaming at the mouth.

Eighteenth Century to Modern Times

Physicians were slow to understand that the heart could be diseased, probably because it was thought to be absolutely essential to life, but in the early eighteenth century two students of dropsy provided the first clues that cardiac disease might not be incompatible with life. One of them, Raymond Vieussens OfMontpellier, correlated the work of Har­vey, Lower, and Malpighi with his own postmortem dissections of dropsy patients. By 1705, he had con­cluded that structural disease of the heart could result in dropsy, after showing how mitral or pulmo­nary stenosis, or aortic insufficiency, could produce the clinical signs of what is now called backward failure. At almost the same time, Giovanni Maria Lancisi was dissecting victims of sudden death in Rome. Although among the last to cite Fernel, his own observations permitted him to recognize that edema, hydrothorax, and ascites could be related to failure of the heart’s propulsive force (i.e., forward failure), to aortic regurgitation, and to obstructions in the right heart. Explicitly recognizing the impor­tance of hydrostatic principles in cardiovascular physiology, Lancisi went on to explain how stagna­tion of blood within the pulmonary vasculature could result in dyspnea, and he learned how to diag­nose hydrothorax ante mortem. He cited Lower’s experiments to support his conclusion that right heart failure could produce engorgement and pulsa­tion of the jugular vein. Thus together Lancisi and Vieussens uncovered the cardiac basis of dropsies of the lungs and thorax.

Their work was expanded a few years later by another of Malpighi’s pupils, Ippolito Francesco Al- bertini, also of Bologna. He echoed his mentor’s conclusion that sluggish circulation through the lungs leads to dyspnea. A frequent dissector, Al- bertini emphasized the time course of dyspnea when he pointed out that it comes on rapidly when obstructions occur in the pulmonary vein of the left heart, resulting in delayed removal of blood from the lungs, erosion of the pulmonary vessels, hemop­tysis, and hydrothorax.

Another interpretation of dropsy arose from Har­vey’s demonstration that the blood circulates within a closed system. In this case, dropsy came to be seen as a febrile disease, because it was usually accompa­nied by a fast pulse, regarded as a cardinal clinical sign of fever over the centuries before clinical ther­mometers became widely available in the 1870s. Thus Thomas Willis, Lower’s mentor and colleague, defined fever as an “intestine motion or commotion of the blood” arising in chemical disturbances like those described over a century earlier by Paracelsus.

Hermann Boerhaave of Leyden was a major propo­nent of the idea that dropsy was a fever, which should be treated accordingly. He based much of his teaching on the work OfFriedrich Hoffmann of Prus­sia, who saw the body as a machine, subject to the effects of mechanical forces. This led Boerhaave to argue that in dropsy, fever is the result of increased cardiac work and increased vascular resistance to blood flow - in short, of friction. Therefore, by his reasoning, dropsy was a fever because it was associ­ated with a fast pulse. At the same time, he postu­lated that dropsical fluid accumulated because defec­tive veins released more fluid into body tissues than those weakened vessels could reabsorb. In Italy, Luca Tozzi, who adopted the newer ideas of Paracelsus, Lower, Malpighi, and Hoffmann, was among the first to differentiate hydrothorax, pulmo­nary edema, and pneumonia at autopsy, which per­mitted him (and, later, Albertini) to differentiate pulmonary and thoracic dropsies ante mortem by palpating the chest and apical impulse of the heart.

A new method for detecting hydrothorax appeared in 1761, when Leopold Auenbrugger of Vienna de­scribed how to strike the chest with the fingers to estimate, by the resonance they produced, the amount and nature of fluid in the pleural cavity and lungs. However, his discovery of percussion added no new information about the pathology of dropsy, and was neglected until it was reintroduced in France in 1808.

The first book devoted to dropsy alone was pub­lished in 1706 by the Leopoldine Academy of Sci­ences in Breslau; its principal author was probably Christianus Helwich. The Academicians described the clinical features of dropsy much as previous au­thors (especially Piso) had done, but they attributed the escape of fluid from the vessels to diminished blood viscosity and to defective vessel walls, as Boerhaave, too, was suggesting.

In 1733, Stephen Hales, a rural English clergy­man, concluded from his experiments in animals that dropsy could be caused by decreased numbers of red blood cells. However, he did not reason that the pau­city of red cells would decrease blood viscosity, much less oncotic pressure. Rather, he thought that the body would compensate for the lack of “red Globules” by heating the blood into a feverish state that re­sulted in dropsy. He was perhaps the first to recognize that inadequate venous return to the heart in dropsy could lead to compensatory (reflex) tachycardia.

Donald Monro of Edinburgh published the second book devoted to dropsy in 1755. He followed Boerhaave in ascribing it to “a weakness and laxity of the fibers... when the vessels do not act with sufficient force,” and listed several factors that would tend to weaken blood vessels: a watery diet, “any great evacuation,” kidney disease, obstruction of small or large vessels, or any debilitating disease. Neither Monro nor later writers mentioned the blood viscosity hypothesis.

In 1763 Samuel Clossey of Dublin and New York applied the principles governing the relationship be­tween pressure and flow velocity, outlined 35 years earlier by Daniel Bernoulli of Basel, to his own stud­ies of the hydrostatic properties of the cardiovascu­lar system. Clossey realized that the development of hydrothorax is a long process, when he computed that it would take about 2 years for 3 pints of hydrothorax fluid to accumulate. He followed Lan- cisi in associating dropsy with weakness of the heart, but postulated that cardiac strength derived from that of the blood vessels.

Thus, regardless of how they were interpreted, the major clinical manifestations of dropsy had been identified by the mid-eighteenth century. Some phy­sicians followed Boerhaave’s dictum that dropsy was caused by weak blood vessel fibers, whereas others attributed the omnipresent dyspnea to weakened cardiac contraction, as did the medical encyclopedist Robert James of London in his Medicinal Dictionary of 1745. But by the turn of the century, unproven - and unprovable - theories of dropsy based on fever, chemical disturbances, blood viscosity, and fiber tone began to fade, and the role of the diseased heart came into sharper focus.

In 1806, Jean-Nicholas Corvisart, who would soon popularize AuenbruggeFs discovery of percussion in French translation, showed how heart disease could produce dropsy, dyspnea, and orthopnea when ve­nous return was slowed. Three years later Allan Burns of Glasgow demonstrated that ossification of the mitral and pulmonary valves leads to right heart dilation and dropsy, although it is not clear whether he was aware of Vieussens’s pioneering observations along the same lines. And in 1835 James Hope of Cheshire showed how myocardial failure results in dyspnea.

In 1813 John Blackall of London was among the first to suggest that dropsy can result from non­cardiac conditions such as liver and kidney disease, when he demonstrated that the albumin content of urine can help differentiate among the underlying causes of dropsy. BlackalFs thesis about renal causes of dropsy was confirmed by Richard Bright, whose careful autopsies at Guy’s Hospital in London led him to report, in 1827, that albumin could be found in the urine of patients with glomerulonephritis who died of dropsy. A few years later, Bright showed that renal disease could also be associated with left ven­tricular hypertrophy, presumably because hyperten- sion is often associated with renal disease. In 1909 C. J. Rothberger and H. Winterberg in Austria, and Thomas Lewis in London, independently showed that a nonanatomic cardiac condition, atrial fibrilla­tion, could produce heart failure, and in 1935 Paul Dudley White and Sylvester McGinn of Boston de­scribed acute cor pulmonale.

Although many details of the pathophysiology of congestive heart failure are still being ascertained, all investigators continue to exploit the relation­ships discovered by Emest Henry Starling at Univer­sity College, London. He noted in 1897 that the strength of heart muscle fiber contraction is propor­tional to fiber length - up to a point. But it was not until 1920 that he adduced experimental evidence to demonstrate the relevance of the rate of blood flow from the veins into the heart, and of the arteries’ resistance to outflow, to his basic “Law of the Heart.” In 1936 Tinsley R. Harrison of Vanderbilt Univer­sity consolidated Starling’s and other surviving con­cepts of heart failure to explain the phenomenon more or less as we understand it today, although heart failure remains the subject of many increas­ingly detailed investigations.

Historical Treatments

The earliest measures for treating dropsy were chiefly attempts to correct humoral imbalances. Cel­sus, 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 Hoffrnann, 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 mid­eighteenth 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 Ofhydrostatic 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