Nitroglycerin-induced improvement in exercise tolerance and hemodynamics in patients with chronic rheumatic heart valve disease.

Nitroglycerin reduces elevated left ventricular filling and pulmonary arterial pressures in resting patients with rheumatic valve disease and reduces symptoms when given over long periods to patients with primary myocardial disease. To determine whether nitroglycerin may prove effective therapeutically in ambulatory patients with heart valve disease, its effects on hemodynamics and exercise capacity were studied in 11 severely symptomatic adults who were already receiving optimal treatment with digitalis and diuretic agents. Seven had predominant mitral valve disease, one had predominant aortic insufficiency and three had equally severe mitral and aortic valve disease. Maximal exercise capacity was assessed with graded treadmill exercise after placebo and after nitroglycerin (0.5 mg sublingually) administered in random sequence to each patient. Exercise capacity (exercise time to limiting fatigue or dyspnea) increased from a mean of 8.3 minutes after placebo to 9.8 minutes after nitroglycerin (P less than 0.005). Eight patients were studied hemodynamically during further intense treadmill exercise. Pulmonary arterial pressure was significantly lower (P less than 0.05) after nitroglycerin than after placebo (mean 44 versus 56 mm Hg), but cardiac output was greater after nitroglycerin (5.0 versus 4.6 liters/min, P less than 0.005). Thus, nitroglycerin appears to increase exericse tolerance and improve the hemodynamic response to exercise in patients with heart valve disease and may be valuable in the long-term pharmacologic therapy of such patients.     

Value of radionuclide ventriculography in the immediate characterization of patients with acute myocardial infarction

The ability of admission radionuclide ventriculography to discriminate among various clinical subsets was evaluated in patients with acute myocardial infarction. One hundred patients with acute myocardial infarction were evaluated within 8 ± 3.1 hours (mean ± standard deviation) after the onset of chest pain. Forty-one patients were in Killip functional class I, 52 in class II and 7 in class III. The mean radionuclide left ventricular ejection fraction was significantly lower in patients with higher Killip classification because of significant elevation of mean left ventricular end-systolic volume rather than significantly altered mean end-diastolic volume. Killip classification frequently failed to correlate with ejection fraction in individual cases. Admission chest X-ray findings were categorized according to the presence of findings suggestive of impaired left ventricular function. Mean left ventricular ejection fraction was significantly lower in patients with abnormal than in patients with normal chest X-ray findings because of significant elevations in both mean end-diastolic and end-systolic volumes. The chest X-ray findings frequently failed to correlate with ejection fraction in individual cases.Stepwise linear regression analysis was employed to analyze the ability of historical, physical, electrocardiographic and chest X-ray findings to predict radionuclide left ventricular ejection fraction. The most predictive variables in order of decreasing significance were anterior myocardial infarction, abnormal chest X-ray findings, rales to two thirds of the posterior thorax, previous myocardial infarction, transmural myocardial infarction and heart rate greater than 100 beats/min. However, even these six optimal predictive variables could explain only 42 percent of the observed variability in left ventricular ejection fraction. Thus, early radionuclide ventriculography adds significantly to the discriminant power of clinical and radiographic characterization of ventricular function in patients with acute myocardial infarction.     

Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy: III. Effects of long-term administration

To determine the efficacy of long-term therapy with verapamil in patients with hypertrophic cardiomyopathy, 78 patients began treatment with the drug in the hospital. Sixty-two patients (79 percent) were in New York Heart Association functional class III or IV despite treatment with beta receptor blocking drugs. Fifty-four percent of all patients evaluated (42 of 78) and 63 percent of those discharged from the hospital (42 of 68) experienced sustained symptomatic improvement 6 to 30 months (median 14 months) after initiation of verapamil therapy. Of these 42 patients in improved condition, 25 had improvement by at least one New York Heart Association functional class, 14 improved by less than one functional class, two felt better taking verapamil than propranolol, and in one patient verapamil controlled asymptomatic ventricular tachycardia. Of the 53 patients who had the obstructive form of the disorder and were considered operative candidates, 25 (47 percent) experienced sufficient improvement so as to forgo operation. In patients remaining on verapamil therapy, the duration of treadmill exercise performed 5 days after the start of verapamil therapy increased by 3.1 ± 0.6 minutes (53 ± 10 percent, p < 0.001) from the value obtained with no medication before verapamil. A further increase of 2.3 ± 0.6 minutes (25 ± 7 percent, p < 0.0025) over the initial value with verapamil was recorded on the patients' last vistt (median 12 months after the start of therapy). Echocardiographic measurements of wall thicknesses and left atrial dimension demonstrated no significant changes during 1 year of verapamil treatment in 31 patients. Administration of verapamil was associated with adverse hemodynamic effects in 9 patients (12 percent) and adverse electrophysiologic effects In 10 (13 percent): Three patients died (with pulmonary edema) and 6 had to have treatment terminated. These results indicate an important role for long-term verapamil therapy in the treatment of hypertrophic cardiomyopathy, but patients must be carefully selected and followed up closely for the development of important adverse hemodynamic or electrophysiologic effects.     

Characteristics of a New Urine, Serum, and Saliva Alcohol Reagent Strip

We have tested an ethanol reagent strip developed at the Addiction Research Foundation of Ontario. Alcohol dehydrogenase and nicotinamide adenine dinucleotide, in the presence of pyrazole, react with ethanol to yield acetaldehyde plus reduced nicotinamide adenine dinucleotide. The latter reduces iodonitrotetrazolium chloride in the presence of diaphorase, generating an intense red color. The rate of color development is proportional to the concentration of ethanol. Color is compared at a specific time against a calibrated color scale ranging from green (negative) to red, representing alcohol concentrations of 0, 25, 50, 100, 200, and 400 mg/dl (0-0.4%; 0-87 mmol/liter). We were able to interpolate the color observed between the calibrated blocks. When tested on urine, serum/plasma, and saliva, ethanol concentration determined by the reagent strip correlates well with ethanol concentration as determined by gas chromatography or by automated enzymatic analysis (r = 0.92-0.98, p less than 0.001; slope 0.83-1.16). The reagent strip was shown to be used appropriately by nonexperienced individuals following a 1-min explanation (reagent strip values, r = 0.92; p less than 0.001, slope = 0.97, versus gas chromatography). The reagent strip does not react with methanol (wood alcohol), isopropanol (rubbing alcohol), and ethylene glycol (antifreeze) often found in accidental poisonings. In 379 clinical samples obtained without exclusion criteria from 12 hospital emergency rooms and a liver clinic, the sensitivity of the reagent strip in detecting ethanol was 98%. Specificity was 99%. The reagent strip was found to have virtually unlimited stability under refrigeration (4 degrees C) and to be stable for 3 to 4 months at room temperature (22-23 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)     

Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart

The digoxin-quinidine interaction was studied in nine healthy human subjects aged 26 to 31 years. A single oral dose (400 mg) of quinidine sulfate administered to subjects taking digoxin resulted in a mean (± standard error of the mean) increase within 1 to 6 hours in the serum digoxin concentration of 0.12 ± 0.01 ng/ml (p <0.0001), an increase of 21 percent. Continued quinidine administration for 24 hours resulted in a 59 percent increase in the mean serum digoxin concentration from 0.68 ± 0.04 to 1.04 ± 0.06 ng/ml (alpha = 0.05). At the same time, however, systolic time intervals demonstrated a lengthening of the mean left ventricular ejection time index from 406 ± 4 to 419 ± 2 ms (alpha = 0.05) and the mean Q?S₂ Index from 524 ± 6 to 532 ± 7 ms (difference not significant [NS]). When compared with the shortening of these intervals predicted from the digoxin dose-response curve if digoxin were the only variable, the lengthening actually observed for both intervals was highly significant. The negative inotropic effect of quinidine administration alone was assessed with systolic time intervals in four subjects. The left ventricular ejection time index lengthened from 419 ± 3 to 425 ± 6 ms (NS) and the Q?S₂ index from 541 ± 6 to 550 ± 7 ms (NS). Therefore, the lengthening of these intervals in subjects taking digitalis after the addition of quinidine represents more than just the negative inotropic effect of quinidine, and occurs despite the increase in serum digoxin concentration.The results of this study support the view that quinidine displaces digoxin from tissue-binding sites as a major mechanism of the interaction. Furthermore, it appears that quinidine may specifically displace digoxin from cardiac-binding sites. These results raise important questions concerning the recommendation to reduce the maintenance digoxin dose when concomitant quinidine therapy is initiated.     

Unusual manifestations of secondary syphilis occurring after orthotopic liver transplantation

A 48-year-old actively homosexual man who had undergone liver transplantation for cirrhosis secondary to hepatitis B infection six years previously presented with a syndrome of diffuse pain, cholestasis, and low-grade fever. The development of thrombocytopenia and persistent hypoprothrombinemia precluded liver biopsy. Subsequently, a skin eruption and VDRL result of 1:128 indicated that most of the findings could be explained by a diagnosis of secondary syphilis with luetic hepatitis and periostitis. This impression was confirmed by a complete response to penicillin therapy. The relation of thrombocytopenia to lues in this case remains uncertain.     

Recognition of left coronary artery fistula to the left and right ventricles by contrast echocardiography

A coronary-cameral fistula was inspected clinically by two-dimensional and pulsed Doppler ultrasound. At cardiac catheterization a fistulous connection between the left coronary artery and the right ventricle was observed. Contrast echocardiography using agitated saline solution injected into the aortic catheter clearly showed the passage of microcavitations into the left and the right ventricles confirming the connection of the fistula to both chambers. Contrast echocardiography is a valuable technique that can help define the site of drainage of coronary artery fistulas.     

Echocardiographic analysis of ventricular septal dynamics in hypertrophic cardiomyopathy and other diseases

It has been suggested that the adynamic or hypokinetic appearance of the ventricular septum is a unique echocardiographic feature of hypertrophic cardiomyopathy (HC). To determine how characteristic of HC the adynamic septum is, 70 patients with this disease, and 31 with other cardiac diseases that produce left ventricular (LV) hypertrophy and pressure overload (aortic valvular stenosis or systemic hypertension), and 25 subjects with normal hearts were studied by echocardiography. On M-mode echocardiography, 53 of 70 patients (75%) with HC had an abnormally low value for percent systolic thickening of the septum associated with either reduced or normal septal excursion; however, 17 patients (25%) showed normal septal dynamics. Twenty of 31 patients (64%) with other cardiac diseases that produce pressure overload showed normal septal thickening and excursion, while 11 (36%) had reduced systolic thickening associated with either diminished or normal excursion. Greatly reduced values for percent systolic thickening of the septum were present both in patients with HC (13 +/- 1%) and in patients with other cardiac diseases (21 +/- 2%). However, differences in systolic septal thickening between the 2 groups were largely a manifestation of the greater absolute diastolic septal thickness in patients with HC. When values for percent systolic thickening were normalized for diastolic septal thickness, or when systolic thickening was compared in only patients with similar diastolic septal thicknesses, differences in septal thickening between patients with HC and those patients with other cardiac diseases were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of plasma propylthiouracil levels with inhibition of thyroid hormone synthesis in the rat

The inhibition of thyroid hormone synthesis was studied in relation to plasma levels of 6-n-propyl-2-thiouracil (PTU). Na ¹²⁵I (5 μCi) was injected i.p. into adult male Sprague-Dawley rats. After 30 min, graded doses of PTU (0.2 mg/kg, 0.1 mg/kg, and 0.05 mg/kg) were similarly injected. Thyroid hormone synthesis was followed by the accumulation of radioactivity into thyroid glands, which were removed at specified time intervals. PTU levels were measured spectrophotometrically at the time of sacrifice. Additionally, PTU (³⁵S) was used to confirm blood levels of PTU and also to follow intrathyroidal PTU levels. Plasma PTU levels in excess of 0.18 μg/ml completely inhibited thyroid hormone synthesis. Levels between 0.14 and 0.09 μg/ml had a partial effect, and PTU levels less than 0.09 μg/ml had no effect on thyroid hormone synthesis.     

Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients

Familial hypercholesterolemia (FH) is characterized by an autosomal codominant inheritance, an abnormality in low-density lipoprotein (LDL) receptor function, elevated plasma cholesterol levels and premature atherosclerosis. Sixteen patients with homozygous FH were studied to correlate the extent of their atherosclerotic disease with their lipid levels and receptor function. The age range at initial presentation was 3 to 38 years (mean 12), and at the last examination, 6 to 43 years (mean 20). The mean pretreatment total plasma cholesterol concentration for all patients was 729 +/- 58 mg/dl (+/- standard error of the mean), and the mean LDL cholesterol level was 672 +/- 58 mg/dl (normal 60 to 176). High-density lipoprotein cholesterol was 28 +/- 3 mg/dl (normal 30 to 74). In the 7 patients with FH who had symptoms of myocardial ischemia (Group I), the mean pretreatment LDL cholesterol value (817 +/- 62 mg/dl) was higher than that of the 9 asymptomatic patients (Group II) (560 +/- 74 mg/dl). In Group I, 5 of 7 patients had left or right coronary ostial narrowing and 3 had significant left ventricular outflow obstruction. Most coronary arterial narrowing occurred in the right coronary and left anterior descending arteries and the least amount in the left circumflex coronary artery. A femoral bruit was the physical finding that correlated best with the Group I population; brother:sister pairs revealed a milder clinical course for the female. Seven of the 16 patients have survived into their third decade without symptoms. Comparison of these persons with those in whom angina developed reveals a marked heterogeneity in their clinical course, which appears to be associated with receptor negative/defective status.