Albert N. Brest

Digitalis toxicity and hypomagnesemia.

Abstract Four patients with digitalis toxicity were found to be hypomagnesemic and normokalemic. A significantly lower mean serum magnesium was noted in a group of digitalized heart failure patients (1.40 mEq./L.) than in matched normal subjects (1.93 mEq./L.). These observations, coupled with the fact that both digitalis and magnesium deficiency lead to a decrease in intracellular potassium, suggested that hypomagnesemia might contribute to the development of digitalis toxicity. To determine whether hypomagnesemia facilitates the development of digitalis toxicity, serial acetyl strophanthidin infusions were performed in 19 adult mongrel dogs. Hypomagnesemia was achieved by Kiil kidney dialysis. While dialysate electrolyte concentration corresponded to normal canine plasma, acetyl strophanthidin was infused (100 μg per minute) three times at three hour intervals. Hypomagnesemia was then induced by three hours of magnesium-free dialysis and acetyl strophanthidin was again infused. Mean serum magnesium was reduced 44 per cent (1.67 to 0.93 mEq./L.). This was accompanied by a 26 per cent reduction in the amount of acetyl strophanthidin needed to produce a toxic arrhythmia (42.4 to 31.4 μg per kilogram). Restitution of sinus rhythm was observed in 13 dogs immediately after the intravenous infusion of 2 to 7 c.c. of 25 per cent magnesium sulfate. These studies have shown that hypomagnesemia facilitates digitalis toxicity which can be promptly terminated with magnesium sulfate. Since diuretic drugs may produce hypomagnesemia as well as hypokalemia and both may predispose to digitalis toxicity, it is suggested that serum magnesium as well as potassium levels be determined in patients with digitalis toxicity.

Pulmonary arteriovenous fistulas: Physiologic and clinical considerations

Abstract The diagnosis of pulmonary arteriovenous fistula is being made with increasing frequency. Since the first antemortem clinical diagnosis in 1939, over two hundred cases have been reported. The syndrome is characterized by cyanosis, dyspnea, digital clubbing and polycythemia, with x-ray evidence of a localized opacity within the lungs. Laminography and angiocardiography aid in the ultimate diagnostic confirmation. Although surgical excision may be indicated when the physiologic abnormalities are severe, operation should probably not be advised in patients without symptoms or with multiple lesions in both lungs. Although not included in the earliest descriptions of this disease, pulmonary arteriovenous fistulas are commonly a manifestation of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease). In a patient with an abnormal pulmonary lesion, the presence of skin or mucous membrane telangiectases or a history of epistaxis, melena or hemoptysis in either the patient or a blood relative suggests the possibility of pulmonary arteriovenous fistula.

Creatinine clearance in renal disease. A reappraisal

To determine the validity of endogenous creatinine clearance as a measure of glomerular filtration rate in patients with renal disease 308 simultaneous determinations of inulin clearance and endogenous creatinine clearance were reviewed and analysed. The ratio of creatinine clearance/inulin clearance increased progressively with the decline in inulin clearance, while the finding of a normal endogenous creatinine clearance masked a definite but mild decrease of glomerular filtration rate in 42% of the patients and a moderate decrease of glomerular filtration rate in 23%. This indicates that with declining glomerular filtration rates the endogenous creatinine clearance progressively overestimates actual glomerular filtration rates. Hence a single determination of creatinine clearance can be misleading as a screening measurement of glomerular filtration rate.

Pharmacodynamic Effects of a New Antihypertensive Drug, Catapres (ST-155)

Catapres is a new imidazoline compound with potent antihypertensive properties. Significant reduction in blood pressure occurs between 1 and 4 hours after oral administration, with the peak effect occurring at 2 to 4 hours and the antihypertensive effect extending for 6 to 10 hours. Blood pressure is reduced in both the supine and erect positions, although the orthostatic response is the more prominent.Cardiac output is reduced moderately in both the supine and erect positions. Peripheral vascular resistance is also reduced, particularly in the erect posture. Accordingly, the cardiac hemodynamic findings suggest that the antihypertensive effect of Catapres is related to the combination of reduction in cardiac output plus decrease in peripheral resistance. Renal blood flow and glomerular filtration rate are preserved in both the supine and erect positions following Catapres administration. Contrasting with the preservation of renal blood flow and glomerular filtration rate, however, is the marked reduction in sodium chloride excretion which follows acute administration of the drug.The clinical utility of the drug was demonstrated in the chronic outpatient study. Although Catapres administered alone exerted only modest antihypertensive effects, a markedly enhanced antihypertensive response was achieved when the drug was combined with a potent oral diuretic, with 80% of patients so treated achieving significant blood pressure reduction in both the supine and erect positions.

Acute renal failure after administration of low-molecular weight dextran.

THE infusion of low-molecular-weight dextran (Dextran 40) has been associated with acute renal failure in 14 patients.14 Three of these cases, not previously reported but submitted to Pharmacia Lab...

PHARMACODYNAMIC EFFECTS OF ALPHA-METHYL DOPA IN HYPERTENSIVE SUBJECTS.

Abstract The decarboxylase inhibitor, alpha-methyl dopa, is a potent antihypertensive agent. The hypotensive action of the drug appears to be due primarily to peripheral arteriolar relaxation. Its ability to reduce renal vascular resistance suggests its potential usefulness in the hypertensive patient with renal functional impairment.

Bilateral carotid sinus nerve stimulation in the treatment of hypertension

Abstract Bilateral carotid sinus nerve stimulation induced significant blood pressure reduction in each of 8 patients with severe essential diastolic hypertension which was previously uncontrolled despite a triple antihypertensive drug regimen. The acute hemodynamic response to bilateral carotid sinus nerve stimulation indicates that the procedure induces its antihypertensive effects as the result of both alpha and beta adrenergic blockade. It appears that the procedure is a useful means of controlling diastolic hypertension, on a long-term basis, especially in patients whose blood pressure is inadequately or incompletely controlled with antihypertensive drugs alone. In those instances in which bilateral carotid sinus nerve stimulation does not by itself reduce diastolic hypertension to normotensive levels, the response to antihypertensive drugs may be substantially enhanced.

Serum and erythrocytic magnesium levels in congestive heart failure

Abstract Pretreatment serum and erythrocytic magnesium levels were found to be significantly lower in patients with congestive heart failure than in control subjects. The erythrocytic sodium level also was lower. The low magnesium and sodium values may be the result of a dilutional intracellular effect or may reflect long term diuretic therapy and possibly diets low in magnesium and sodium. The administration of hydrochlorothiazide did not significantly affect serum or erythrocytic cation levels. Absence of the expected decrease in serum magnesium subsequent to the administration of hydrochlorothiazide may be due to the fact that the pretreatment serum levels were significantly lower than in normal subjects. It is suggested that, in patients with congestive heart failure, low serum and intracellular magnesium levels may contribute to the development of digitalis toxicity, even in the presence of normal serum potassium levels. Although the patients with congestive heart failure were normotensive, changes in diastolic blood pressure induced by hydrochlorothiazide correlated with changes in serum magnesium as well as with changes in the ratio of erythrocytic potassium to serum magnesium.

Pharmacodynamic effects and clinical use of alpha methyldopa in the treatment of essential hypertension

Abstract The availability of decarboxylase inhibitors provides a new biochemical means for controlling blood pressure in patients with diastolic hypertension. The decarboxylase inhibitor, alpha methyldopa, is a potent antihypertensive agent which produces a predominant orthostatic response. The hypotensive action of the drug appears due to peripheral arteriolar relaxation and accompanying reduction in cardiac output. Its ability to reduce renal vascular resistance suggests potential usefulness in the hypertensive patient with renal functional impairment as well.

Myocardial infarction without obstructive coronary artery disease

Abstract The present report describes five cases of transmural myocardial infarction occurring in patients without occlusive coronary artery disease or other discernible abnormalities. It is apparent from these cases and others described in the literature that such patients may present with or without angina and, in some, the clinical course will be complicated by recurrent infarction and/or significant residual myocardial dysfunction. At present the exact incidence and natural history of this syndrome is unclear. Undoubtedly the increasing application of coronary arteriography will identify many more such patients. Delineation of the genesis and the full clinical spectrum of myocardial infarction without coronary artery disease warrants further investigative attention.