Frank I. Marcus

Digoxin Metabolism in the Elderly

Tritiated digoxin (0.5 mg) was given intravenously to five elderly men (mean age, 77 years) and nine young men (mean age, 27 years). The elderly were not in congestive heart failure. The serum creatinines of the old and young were not different. However, the creatinine clearance averaged 56 ml/min/1.73 m2 in the old and 122 ml/min/1.73 m2 in the young (P<0.001). Digoxin clearance averaged 53 ml/min/1.73 m2 in the old and 83 ml/min/1.73 m2 in the young (P<0.001). The blood concentrations of tritiated digoxin were significantly higher in the elderly throughout the study (P<0.05). When blood digoxin concentrations were corrected for body surface area, there was no significant difference between the two groups during the first 24 hr, but thereafter the concentrations in the elderly were higher.The same dose of digoxin resulted in higher blood concentrations and longer blood half-life in the elderly. This is due to the smaller body size and a diminished urinary excretion of digoxin in the elderly.

Administration of Tritiated Digoxin with and without a Loading Dose A Metabolic Study

IN 1919, Pardee attempted to assess the daily maintenance requirements of digitalis.1 He administered digitalis to patients in small repetitive doses until toxicity occurred. Digitalis was then withheld for some days and the patients were again given digitalis until toxicity developed. He calculated that the amount required to achieve toxicity the second time minus that required the first time divided by the number of days was equal to the daily elimination of digitalis. Thus, a fixed daily rate of excretion was assumed in these calculations. However, in 1923, Gold2 demonstrated that animals did not eliminate a fixed quantity of digitalis in a unit of time, but rather excreted a fraction of the amount present. He then proceeded to confirm the lack of a fixed rate of excretion in man. In 1929, Gold and DeGraff3 stated that digitalis cumulation tends to be a self-limiting process; that a given dose of digitalis may show evidence of cumulation at first and later cease to show cumulation when the same daily dose is continued.... In other words, as the quantity of digitalis in the body increases, the amount eliminated daily also increases until the quantity eliminated equals the daily dose; then further cumulation no longer occurs. The intensity of digitalis action present at the time that cumulation ceases depends on the size of

THE HEMODYNAMIC EFFECT OF THE VALSALVA MANEUVER IN MUSCULAR STENOSIS.

Abstract A patient with muscular subaortic stenosis underwent hemodynamic studies on four separate occasions. At cardiac catheterization, there was a peak systolic gradient of 10 to 20 mm. Hg between the left ventricle and the brachial artery. The effective orifice size was 2 to 4 square centimeters. This gradient increased to 95 mm. Hg when isoproterenol was infused. During the strain of the Valsalva maneuver a gradient of 95 mm. Hg was induced; this regressed rapidly upon release of straining. Concomitantly, the cardiac output decreased by 61 per cent, and the stroke volume by 69 per cent of resting values. The calculated orifice size was 0.2 square centimeter. When simultaneous left ventricular and brachial arterial pressures were measured in a patient with left ventricular hypertrophy due to hypertension, and in a normotensive patient, no pressure gradient developed between the left ventricle and aorta during the Valsalva maneuver. All the drugs or maneuvers associated with an increase in left ventricular obstruction in muscular subaortic stenosis, including the Valsalva maneuver, have in common a decrease in cardiac size or in end-systolic volume. These findings lend support to the view that, with more complete left ventricular emptying, a greater opportunity is afforded for approximation of the already narrowed ventricular outflow tract, with resultant obstruction in late systole.

Muscular subaortic stenosis: Clinical and pathologic observations in an elderly patient☆

Abstract The clinical and pathologic findings in a 74 year old Negro woman with muscular subaortic stenosis are reported. The clinical diagnosis was suggested by the combination of a brisk-rising carotid pulse, a bifid left ventricular precordial impulse, a prominent atrial diastolic gallop and an apical pansystolic murmur with postpremature beat accentuation. At necropsy there was severe hypertrophy of the cephalad portion of the ventricular septum, thickening of the endocardium of the outflow portion of the left ventricle and focal fibrous thickening of the mitral valve leaflets.

The use of amyl nitrite in the hemodynamic assessment of aortic valvular and muscular subaortic stenosis

Abstract The hemodynamic effects of amyl nitrite were studied in 4 patients with valvular aortic stenosis and in 4 patients with muscular subaortic stenosis. In all 8 subjects, amyl nitrite significantly increased the left ventriculo-aortic gradients. Two patients in each group had nondiagnostic gradients in control tracings but had diagnostic postinhalation gradients. These observations indicate that the inhalation of amyl nitrite is a safe, convenient, and reproducible means of accentuating the gradient in both fixed-orifice aortic stenosis and muscular subaortic stenosis. Mechanisms relating to the development of increased obstruction of the outflow tract are believed to differ in the two groups.

Perfusion and ventilation radioisotope lung scans in stenosis of the pulmonary arteries and their branches

Abstract In ten patients with stenosis of the pulmonary arteries, the relative distribution of right and left pulmonary blood flow was related to the localization of the coarctation by angiography and the degree of stenosis. To evaluate the distribution of pulmonary blood flow, the scintillation lung scan after injection of 131 I macroaggregated albumin (MAA) was utilized. Scintillation scanning of the lungs after inhalation of xenon-133 gas was also performed to assess the distribution of ventilation. The relative right to left pulmonary arterial blood flow distribution showed a good correlation with the catheterization pressure gradients and the angiographic findings. The distribution of ventilation was relatively unaffected. In a patient with a precordial murmur that exhibits disproportionate radiation to the axilla and back, an altered distribution of right to left perfusion helps to substantiate the diagnosis of stenosis of the pulmonary arteries. However, if the obstruction is bilateral and of equal degree, the distribution of blood flow may be normal. In patients with isolated acyanotic left to right shunts, the right to left distribution of pulmonary blood flow is apparently unaltered so that a lateral shift from the normal pattern raises the question of stenosis of the pulmonary arteries as an additional lesion. The finding of patchy areas of decreased radioactivity in both perfusion and ventilation lung scans in four of ten patients suggest that there may be a high incidence of emphysema or other lung disease in these patients.

Aortic insufficiency secondary to spontaneous rupture of a fenestrated leaflet

Abstract Spontaneous rupture of a fenestrated valve leaflet is one of the unusual causes of severe aortic insufficiency. A case is presented of an elderly woman with severe aortic insufficiency who was shown at autopsy to have rupture of a fenestrated valve leaflet. A review of the English literature revealed 4 other cases of spontaneous rupture of a fenestrated aortic valve leaflet. In these cases, as in ours, the patient had either hypertension or syphilitic aortitis in addition to the valvular fenestrations. It would appear that the weakened fenestrated valve in conjunction with the additional stress imposed on the aortic valve by systemic hypertension or syphilitic aortitis are factors which predispose to spontaneous rupture.

Aortic regurgitation in the elderly

Abstract The incidence of aortic insufficiency was determined in 291 patients over the age of 65 who were admitted consecutively to the medical services of the District of Columbia General Hospital. The subjects were examined independently by three physicians for the presence of a diastolic blowing murmur. Twelve per cent of the patients had a murmur characteristic of aortic insufficiency. Other causes of a diastolic blowing murmur were excluded clinically. Syphilis appeared to be a major cause of aortic regurgitation, since serologic evidence to substantiate this diagnosis was found in 72 per cent (23 of 32) of the patients with aortic incompetence. In this age group, 7.9 per cent of the patients admitted to this hospital had aortic regurgitation associated with syphilis. These data suggest that syphilis may be a common contributing cause of incompetence of the aortic valve in such a patient population as that on which our study was based. The pathogenesis of aortic incompetence in those patients with syphilis who did not have characteristic chest roentgenographic evidence of the disease may be a minimal aortitis which accentuates the normal aging process of aortic dilatation. Of patients examined, 3.1 per cent had idiopathic aortic regurgitation. Treatment of anemia, congestive heart failure, or hypertension did not result in disappearance of the murmur. The murmur was undetected by the ward physicians in 53 per cent of the patients with aortic insufficiency. Although it has been recognized that the faint diastolic blowing murmur is frequently over-looked, this is the first time that the extent of this error has been documented. It is recommended that, when the murmur is found, antibiotic prophylaxis for bacterial endocarditis be instituted.

THE USE OF THE VALSALVA MANEUVER TO DIFFERENTIATE FIXED-ORIFICE AORTIC STENOSIS FROM MUSCULAR SUBAORTIC STENOSIS.

Abstract The response to the Valsalva maneuver was observed in 10 patients with fixed-orifice aortic stenosis and 3 patients with muscular subaortic stenosis. In the patients with fixed-orifice aortic stenosis the peak systolic gradient either remained essentially unchanged or decreased. This was due to a decrease in left ventricular systolic pressure equal to or greater than the decline in arterial pressure. In the subjects with muscular subaortic stenosis the peak systolic gradient increased with straining, an effect caused by a rise in left ventricular systolic pressure while arterial systolic pressure declined. The mechanism for the difference in the responses was discussed. The peripheral pulse tracing during the Valsalva maneuver was found to differ in contour in the two groups studied. The conclusion is that the response to the Valsalva maneuver is of aid in the hemodynamic differentiation of fixed-orifice aortic stenosis from muscular subaortic stenosis.