Normal and chronically hypokalemic dogs were infused with Hdigoxin until ventricular tachycardia occurred, at which point the concentration of digoxin was measured in all tissues involved in vision. ...The highest concentration was found in the choroid-retina of the eye, and this was considered the most likely site for the various visual changes seen in digitalis intoxication in man. Chronic hypokalemia did not influence the concentration or distribution of digoxin in the optic tract. It is speculated that the increased digoxin level in the extracranial part of the optic nerve is due to a weakness in the blood-retina barrier where the optic nerve fibers pass through the retina. One eye was left in situ for 3 days after death to study post-mortem changes in digoxin distribution. Vitreous humor analysis is being used to study the cause of death in man, but we found an increase in the vitreous humor digoxin level after death due to loss from its primary binding site in the choroid-retina. A similar effect would be expected with any drug bound to the retina and would have to be taken into account when considering the cause of death in forensic pathology.
The mobile coronary care unit Binnion, P F; Mandal, S; Makous, N
JAMA : the journal of the American Medical Association,
02/1973, Letnik:
223, Številka:
8
Journal Article
Angiotensin infused at 0.05 mcg/kg per min for 30 minutes into anesthetized dogs reduces cardiac output, raises arterial blood pressure, increases total peripheral resistance, but does not raise ...right ventricular pressure nor change left ventricular stroke work. It is suggested that this infusion rate may be comparable to the rate of production under certain conditions.The cardiovascular action of epinephrine given at rates similar to those occurring under stress, namely 0.1 mcg/kg per min and 0.2 mcg/kg per min for 30 minutes, are discussed. In the former dose no cardiovascular effects are seen, but with the latter dose the usual cardiovascular effects were observed.A transient augmentation of effect on cardiac output and stroke work is noted with a combination of epinephrine 0.1 mcg/kg per min and angiotensin 0.05 mcg/kg per min, and of stroke work alone when the dose of each is doubled. It is suggested that the physiological importance of this interaction may be limited to the initial phases of certain stresses in which both these substances are released. The mechanism of this effect is not clear, but may be the result of the interaction of epinephrine, angiotensin and aldosterone.
Catheterization of the left heart permits sophisticated assessment of the mechanical problem in aortic stenosis. Selection of patients for surgical repair requires an additional judgment regarding ...the contractile state of the left ventricle. Angiotensin has recently been used to study the function of the unobstructed left ventricle by imposing controlled pressure loads on both compensated and failing human hearts. The present study was designed to determine whether angiotensin might be of value in characterizing left ventricular function in the presence of aortic stenosis. Accordingly, controlled amounts of the drug were infused during transseptal left heart catheterization in 12 patients in whom fixed obstruction to left ventricular outflow was the sole mechanical fault. Observations were made before and during a series of stepwise increments in systemic systolic pressure. The following information was obtained: cardiac rate, stroke volume, peripheral vascular resistance, left ventricular systolic and end-diastolic pressures, brachial arterial systolic and diastolic pressures, aortic gradient, left ventricular stroke work, systolic ejection period, and aortic valve area. Left ventricular function curves were constructed by relating stroke work to diastolic filling pressure. Rises in brachial systolic pressure exceeded rises in left ventricular systolic, regularly diminishing the gradients. Elevations in systemic arterial pressure consistently elevated left ventricular end-diastolic pressure, indicating that angiotensin can be used to impose a pressure load on the left ventricle despite the interposition of fixed obstruction. In an attempt to gain further information on the mechanical and myocardial factors that coexist in aortic stenosis, three types of observations were made regarding the hemodynamic response of the left ventricle to the graded pressure loads: (1) the directional changes in stroke volume accompanying the increments in ventricular stress, (2) the magnitude of the increase in left ventricular systolic pressure accompanying a given increment in diastolic filling pressure, and (3) the relation between ventricular end-diastolic pressure and stroke work (ventricular function curves). Although the individual responses did not uniformly distinguish mechanical from myocardial influences, when stroke volume, left ventricular end-diastolic pressure, and ventricular function curves were taken together, a clearer impression of the behavior of the left ventricle emerged. Such information may prove useful in view of the practical need to assess ventricular adequacy in aortic stenotic patients considered for corrective surgery.
The absorption of digoxin tablets Binnion, Peter F.
Clinical pharmacology and therapeutics,
November 1974, Letnik:
16, Številka:
5part1
Journal Article
Recenzirano
The digoxin in tablets from 4 different manufacturers was measured and found to be the same. The disintegration times for these tablets were different, and this measurement did not correlate with the ...plasma levels in subiects who took them. The tablet with the slowest disintegration rate produced satisfactory plasma digoxin concentrations. Another tablet, with slow dissolution rate, failed consistently to produce a therapeutic plasma level. All packages containing digoxin tablets should be labeled with data on their dissolution characteristics, but none should be sold unless these data are consistent with biologic availability.
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