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A gas chromatographic assay for digoxin
ABSTRACTS
tients had left ventriculography. One had unusual thickening of the left ventricular myocardium; in the others left ventricular anatomy and function were normal. In each patient CHF was controlled medically. One patient was operated on at 5 months of age and died. One patient died suddenly of unknown cause at age 34 months. The ASD closed spontaneously in 1. Two patients had elective closure of the ASD; the remaining 4 are asymptomatic and awaiting elective closure. Careful hemodynamic evaluation did not disclose the cause of CHF. In 2 patients right and left heart catheterization during and after CHF (1 to 3 years later) revealed virtually identical hemodynamic features. Emergency operation in infancy does not appear warranted in the infant with ASD and CHF.
This fibroblastic response can involve short segments of veins or, more commonly, the entire vein. The angiographic appearances are typical and have been seen in 15 patients. Occlusion as early as 2 months after surgery has been shown to be due to fibroblastic proliferation. In 2 patients, 1 vein graft has remained unchanged while another is diffusely involved. No factors have so far been correlated with the occurrence of this lesion. No aneurysms have been demonstrated. Typical gross and histologic pictures will be presented as well as angiographic findings. More widespread recognition of the condition may lead to knowledge of causative factors for this entity which clearly limits the duration of benefit some patients receive from these vein grafts.
A Gas Chromatographic Assay for Digoxin Hemodynamic History of Congenital Aortic Stenosis in Childhood ROGER A. HURWITZ,
MD, FACC, Indianapolis,
SUMNER California Indiana
The hemodynamic course of congenital aortic stenosis was studied by serial catheterization of 14 children. Right- and left-sided cardiac catheterization and cineangiography was performed in all children on 2 occasions. Sedation, equipment and general catheterization protocol were similar. No intervening surgical procedure had been performed, nor was subacute bacterial endocarditis diagnosed during the interval between catheterizations. The average initial resting left ventricular-aortic systolic gradient was 53 mm Hg. Six children had moderately severe or severe stenosis with gradients higher than 50 mm Hg. Repeat catheterization at an average time interval of 5 years revealed the group to have no significant change in gradient. Although the gradient increased enough in 3 cases to make these children more likely surgical candidates, cardiac output was definitely comparable in only 1 instance. Retrograde aortograms demonstrated a significant increase in aortic insufficiency in 3 children. This study confirms the previously held clinical impression that the gradient of congenital aortic stenosis usually remains constant during childhood. However, there is some tendency for further development of aortic insufficiency even in the absence of cardiac surgery or subacute bacterial endocarditis.
Late Changes in Coronary Vein Grafts W. DUDLEY JOHNSON, MD; JAMES TECTOR, MD, Milwaukee, Wisconsin
E. AUER,
MD; ALFRED
J.
The use of saphenous vein grafts to reestablish coronary flow is now a commonly performed procedure. While the initial patency rate exceeds 90%, repeat studies now being performed 1 to 2 years later show a small, but definite rate of late occlusion and a higher rate of change in angiographic appearance. Two patients underwent reoperation for replacements of vein grafts, and a third was examined at autopsy 11/2 years later. All veins showed similar changes involving massive subintimal fibroblastic hyperplasia.
640
M. KALMAN,
MD; ERIC WATSON,
MS, Stanford,
A gas chromatographic method for the assay of digoxin in human serum has been developed. Digoxin is extracted from serum with methylene chloride, separated by thin layer chromatography (TLC) from interfering substances, and reacted with heptafluorobutyric anhydride to form the digoxigenin-heptafluorobutyrate (DHB). The DHB is purified by another TLC step, and an aliquot is injected into a gas chromatograph equipped with an electron capture detector. Two controls are included in the assay: (1) radioactive 3H-digoxin is added to the sample of serum to determine the percent recovery, and (2) digitoxin heptafluorobutyrate is added to the final DHB sample as an internal standard. The method is specific for digoxin. It has been applied to samples of sera from patients receiving digoxin. Currently we are extending the method to analysis of urine for digoxin and for metabolites of digoxin.
Natural History of Angina Pectoris: Prognosis and Survival. The Framingham Study WILLIAM B. KANNEL, MD, FACC: MANNING FEINLEIB, MD, DPH, Framingham, Massachusetts and Bethesda, Maryland
Most studies of the natural history of angina are handicapped by samples nonrepresentative of the total disease experience. The evolution of 303 cases of angina in a general population sample of 5,127 persons was ascertained and reveals that the lot of the angina victim is not a happy one. Prognosis as to survival and progression to more serious coronary manifestations was distinctly ominous. One in 4 men with angina in this study had a myocardial infarction or died from coronary heart disease within 5 years, half of those over age 45 within 8 years. The risk is half this for women. About 30% of those over 55 will die within 8 years, and a third of these deaths will be sudden. Mortality was close to that which follows the post-hospital phase of myocardial infarction. Surprisingly, survival in men with uncomplicated angina was no better than in those with angina following an infarction. Angina was more likely to be the presenting com-
The
American
Journal
of
CARDIOLOGY
tients had left ventriculography. One had unusual thickening of the left ventricular myocardium; in the others left ventricular anatomy and function were normal. In each patient CHF was controlled medically. One patient was operated on at 5 months of age and died. One patient died suddenly of unknown cause at age 34 months. The ASD closed spontaneously in 1. Two patients had elective closure of the ASD; the remaining 4 are asymptomatic and awaiting elective closure. Careful hemodynamic evaluation did not disclose the cause of CHF. In 2 patients right and left heart catheterization during and after CHF (1 to 3 years later) revealed virtually identical hemodynamic features. Emergency operation in infancy does not appear warranted in the infant with ASD and CHF.
This fibroblastic response can involve short segments of veins or, more commonly, the entire vein. The angiographic appearances are typical and have been seen in 15 patients. Occlusion as early as 2 months after surgery has been shown to be due to fibroblastic proliferation. In 2 patients, 1 vein graft has remained unchanged while another is diffusely involved. No factors have so far been correlated with the occurrence of this lesion. No aneurysms have been demonstrated. Typical gross and histologic pictures will be presented as well as angiographic findings. More widespread recognition of the condition may lead to knowledge of causative factors for this entity which clearly limits the duration of benefit some patients receive from these vein grafts.
A Gas Chromatographic Assay for Digoxin Hemodynamic History of Congenital Aortic Stenosis in Childhood ROGER A. HURWITZ,
MD, FACC, Indianapolis,
SUMNER California Indiana
The hemodynamic course of congenital aortic stenosis was studied by serial catheterization of 14 children. Right- and left-sided cardiac catheterization and cineangiography was performed in all children on 2 occasions. Sedation, equipment and general catheterization protocol were similar. No intervening surgical procedure had been performed, nor was subacute bacterial endocarditis diagnosed during the interval between catheterizations. The average initial resting left ventricular-aortic systolic gradient was 53 mm Hg. Six children had moderately severe or severe stenosis with gradients higher than 50 mm Hg. Repeat catheterization at an average time interval of 5 years revealed the group to have no significant change in gradient. Although the gradient increased enough in 3 cases to make these children more likely surgical candidates, cardiac output was definitely comparable in only 1 instance. Retrograde aortograms demonstrated a significant increase in aortic insufficiency in 3 children. This study confirms the previously held clinical impression that the gradient of congenital aortic stenosis usually remains constant during childhood. However, there is some tendency for further development of aortic insufficiency even in the absence of cardiac surgery or subacute bacterial endocarditis.
Late Changes in Coronary Vein Grafts W. DUDLEY JOHNSON, MD; JAMES TECTOR, MD, Milwaukee, Wisconsin
E. AUER,
MD; ALFRED
J.
The use of saphenous vein grafts to reestablish coronary flow is now a commonly performed procedure. While the initial patency rate exceeds 90%, repeat studies now being performed 1 to 2 years later show a small, but definite rate of late occlusion and a higher rate of change in angiographic appearance. Two patients underwent reoperation for replacements of vein grafts, and a third was examined at autopsy 11/2 years later. All veins showed similar changes involving massive subintimal fibroblastic hyperplasia.
640
M. KALMAN,
MD; ERIC WATSON,
MS, Stanford,
A gas chromatographic method for the assay of digoxin in human serum has been developed. Digoxin is extracted from serum with methylene chloride, separated by thin layer chromatography (TLC) from interfering substances, and reacted with heptafluorobutyric anhydride to form the digoxigenin-heptafluorobutyrate (DHB). The DHB is purified by another TLC step, and an aliquot is injected into a gas chromatograph equipped with an electron capture detector. Two controls are included in the assay: (1) radioactive 3H-digoxin is added to the sample of serum to determine the percent recovery, and (2) digitoxin heptafluorobutyrate is added to the final DHB sample as an internal standard. The method is specific for digoxin. It has been applied to samples of sera from patients receiving digoxin. Currently we are extending the method to analysis of urine for digoxin and for metabolites of digoxin.
Natural History of Angina Pectoris: Prognosis and Survival. The Framingham Study WILLIAM B. KANNEL, MD, FACC: MANNING FEINLEIB, MD, DPH, Framingham, Massachusetts and Bethesda, Maryland
Most studies of the natural history of angina are handicapped by samples nonrepresentative of the total disease experience. The evolution of 303 cases of angina in a general population sample of 5,127 persons was ascertained and reveals that the lot of the angina victim is not a happy one. Prognosis as to survival and progression to more serious coronary manifestations was distinctly ominous. One in 4 men with angina in this study had a myocardial infarction or died from coronary heart disease within 5 years, half of those over age 45 within 8 years. The risk is half this for women. About 30% of those over 55 will die within 8 years, and a third of these deaths will be sudden. Mortality was close to that which follows the post-hospital phase of myocardial infarction. Surprisingly, survival in men with uncomplicated angina was no better than in those with angina following an infarction. Angina was more likely to be the presenting com-
The
American
Journal
of
CARDIOLOGY