Radionuclide analysis of peak filling rate, filling fraction, and time to peak filling rate. Response to supine bicycle exercise in normal subjects and patients with coronary disease

Using gated equilibrium radionuclide angiography, variables of diastolic filling were analyzed at rest and during supine bicycle exercise in normal subjects (Group 1, n = 18), coronary patients with normal resting ejection fractions (Group 2, n = 26), and coronary patients with reduced resting ejection fractions (Group 3, n = 8). Indexes analyzed were peak filling rate and filling fraction during the first third of diastole. At rest, the peak filling rate was significantly lower in coronary patients than in normal subjects (3.18 +/- 0.82 end-diastolic volume [EDV]/s in Group 1 versus 2.41 +/- 0.66 EDV/s in Group 2, p less than 0.005; and 1.34 +/- 0.26 EDV/s in Group 3, p less than 0.001 versus Group 1). These differences persisted at peak exercise. Coronary patients also had significantly lower filling fractions at rest and during exercise than did normal control subjects. The time from end-systole to peak filling rate was longer at rest in patients in Group 2 (203 +/- 52 ms) than in subjects in Group 1 (172 +/- 50 ms, p less than 0.025). This remained true when the time to peak filling was normalized by the R-R interval. Although the exercise time to peak filling was longer in coronary patients in both Groups 2 and 3 than in Group 1, these differences were not apparent when the interval was normalized by the R-R interval. Thus, abnormalities in peak filling rate and filling fraction exist in patients with coronary disease both at rest and during exercise, but large overlaps exist between normal and coronary patients. Caution is advised in comparing the timing of events during diastole because apparent group differences may be related in part to rest or exercise heart rate.     

Sensitivity and specificity of nuclear phase analysis versus ejection fraction in coronary artery disease

Phase standard deviation (SD) and skew characteristics of the first Fourier harmonic of equilibrium radionuclide volume curves were examined and compared during rest and during supine bicycle exercise with ejection fraction (EF) changes and the development of ischemia in 17 control subjects and in 2 groups of patients (n = 57) with coronary artery disease (CAD). Group I comprised 37 patients with CAD; IA was a subgroup of 20 patients with previous myocardial infarction (MI) and IB a subgroup of 17 patients with CAD without MI (all with coronary stenosis greater than 75% diameter narrowing). Group II comprised 20 patients with CAD who had undergone coronary bypass surgery. In the Group I subjects, phase SD was the most sensitive indicator of CAD at rest (Group I, 56%; Group IA, 70%, and Group IB, 29%), and the EF was the most sensitive indicator at submaximal (Group I, 78%; Group IA, 86%, and Group IB, 64%) and maximal exercise (Group I, 70%; Group IA, 93%, and Group IB, 53%). When phase SD and skewness were combined with EF changes, little increase in sensitivity occurred in Group I (rest 61%, submaximal exercise 88% and maximal exercise 76%). The results from Group II subgroups were qualitatively similar to those observed with Group I subgroups. These data reveal a marginally improved sensitivity for detection of CAD during supine bicycle radionuclide ventriculography when phase measurements were added to changes in global EF values.     

Investigation of insulin resistance during diabetic ketoacidosis: role of counterregulatory substances and effect of insulin therapy.

It has been generally accepted that insulin resistance (IR) exists in diabetic subjects during episodes of ketoacidosis (DKA). However, little experimental data exist regarding this question. We have studied IR in nine untreated diabetic subjects (mean age 20 yr) both during their initial episode of DKA and after 2–7 wk of insulin therapy. The experimental protocol consisted of a 150-min intravenous infusion of glucose (6 mg/kg/min) and insulin (80 mU/min). Under these conditions steady-state plasma glucose (SSPG) and insulin (SSPI) levels were reached by 90 min and maintained for the duration of the study. Since all subjects achieved similar SSPI and all received the same glucose load, the SSPG could be used as a measure of an individual's IR. In addition, steady-state plasma levels of glucagon, cortisol, growth hormone, and free fatty acids were measured in an attempt to gain insight into their roles in the maintenance of IR during DKA. Although mean (± SE) SSPI levels were the same during both study periods (93 ± 4 versus 92 ± 4 μU/ml), there was a marked difference between the initial and posttherapy SSPG levels for the nine subjects 342 ± 32 versus 104 ± 16 mg/100 ml,p < .001). Mean steady-state plasma levels of growth hormone, corticol, and free fatty acids were significantly higher during the initial studies, but only cortisol and free fatty acid levels correlated significantly with their corresponding SSPG levels. Steady-state plasma glucagon levels were the same during both study periods, and individual levels did not correlate with associated SSPG levels. These studies demonstrate that significant IR was present in these subjects during DKA as compared to the posttherapy period. Furthermore, the results suggest that while increased plasma concentrations of cortisol and free fatty acids may be involved in the maintenance of IR during DKA, elevated levels of plasma growth hormone and glucagon are not necessary for this phenomenon.     

Intravenous and oral prenalterol in congestive heart failure. Effects on systemic and coronary hemodynamics and myocardial catecholamine balance

Systemic and coronary hemodynamic effects of prenalterol, a beta-1 receptor agonist, were determined in patients with chronic congestive heart failure, initially after intravenous administration (10 patients) and then after oral administration (eight patients). Cardiac index increased by 33 percent and 30 percent after intravenous and oral prenalterol, respectively. The increase in stroke volume index and stroke work index and decrease in pulmonary capillary wedge pressure and systemic vascular resistance were not significant. Myocardial oxygen consumption and coronary sinus blood flow increased in the majority of patients, although these changes were not statistically significant. There were no significant changes in transmyocardial norepinephrine or epinephrine balance. The systemic and coronary hemodynamic effects of both intravenous and oral prenalterol were similar. Major side effects included sudden death (two patients) and hypotension and bradycardia (three patients) during oral prenalterol treatment. It is concluded that improved left ventricular function following both intravenous and oral prenalterol may be associated with increased myocardial oxygen consumption, and serious adverse effects may occur during prenalterol therapy.     

Inorganic phosphate treatment of nephrolithiasis

We report the results of long-term inorganic phosphate therapy in 47 patients suffering from recurrent calcium-containing urinary calculi. Forty-five patients had hypercalciuria before treatment. Phosphate therapy had no effect on urinary calcium excretion or stone passage but did appear to reduce the need for lithotomy. The stone passage-removal rate in the 5 years before therapy was 1.3 per patient per year and fell to 0.8 in the years of treatment (mean 5.5 years). The lithotomy rate fell from 0.12 per patient per year to 0.04 with treatment (p < 0.01). Patients who were free of stones at the start of the therapy fared best. Significant decreases in serum alkaline phosphatase were noted in many patients, possibly a sign of healing subclinical osteomalacia.     

Periods of differing mortality distribution during the first year after acute myocardial infarction

The mortality rate after acute myocardial infarction (AMI) has generally been modeled by a single exponential function. The present study was undertaken to determine, in 3 different populations, whether or not periods exist during the first year after AMI which have mortality distributions that differ from this pattern. The 3 patient populations included San Diego (346 patients, 71 deaths), Vancouver (704 patients, 146 deaths), and Copenhagen (1,140 patients, 262 deaths). Hospital admission was within 24 hours of the onset of symptoms, and patients dying within the first 24 hours after hospital admission or of noncardiac or unknown causes were not analyzed. The mortality between 2 and 21 days in the combined data base was 11.4% (range 10.9 to 11.7) and from 3 weeks to 1 year 10.5% (range 9.0 to 11.3). A high degree of similarity was noted among the shapes of the 3 survival curves. The hypothesis of an exponential mortality rate during the entire first year was rejected. Using a special statistic, changepoints at days 17,23, and 24 in the 3 populations (21 days for the combined data base) were identified and used thereafter to divide the year into 2 separate periods of mortality within which exponentiality for the mortality rate was not rejected. The point by which exactly 50% of deaths had occurred was day 19, with 75% of deaths occurring by day 100. These data further define the natural history after AMI and indicate optimal follow-up periods for short- and longer-term management strategies based on risk assessment or trials of risk reduction after AMI.     

Plasma testosterone stimulation-suppression dynamics in hirsute women. correlation with long-term therapy

Clinical response and changes in plasma testosterone were measured in 22 hirsute women during the administration of dexamethasone, ethinyl estradiol-medroxyprogesterone, or both. The response of plasma testosterone to the administration of adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (HCG) and dexamethasone was measured before treatment in 16 patients, and six additional patients were treated without initial testing. Patients were treated with three month courses of each therapy, regardless of their test results. Results of short-term testing did not correlate with those of long-term treatment. Previously elevated testosterone levels were suppressed in 80 per cent of the patients treated with dexamethasone and in all the patients treated with ethinyl estradiol-medroxyprogesterone (EE-MP).Hirsutism diminished in a third of the patients treated with dexamethasone and in half of the patients treated with EE-MP. Acne diminished in half of the patients with either therapy. There was good correlation between normalization of plasma testosterone levels and clinical improvement.Normal plasma testosterone levels were maintained for several months after dexamethasone treatment was discontinued.Recommendations are given for the approach to diagnosis and treatment of the female patient with hirsutism.     

Atrial reentry in chronic repetitive supraventricular tachycardia

Atrial reentrance as a mechanism of the tachycardia was demonstrated in a 28-year-old patient suffering from chronic repetitive supraventricular tachycardia. Criteria for diagnosis included the following: (1) Repetitive supraventricular tachycardia was induced and terminated by properly timed atrial extrastimuli. (2) Return cycles of all atrial extrastimuli not abolishing the tachycardia were fully compensatory. (3) A-H prolongation was not a prerequisite to induce the tachycardia. (4) The contours of P and A waves during tachycardia differed from those in sinus rhythm, but atrial activation remained antegrade. (5) A concealed anomalous pathway could not be proved.     

Increased physical activity: A protective factor against heart attacks in Puerto Rico

The incidence and potential risk factors of coronary heart disease were assessed in 2,585 rural and 6,208 urban men, aged 45 to 64 years, participating in the Puerto Rico Heart Health Program, a prospective epidemiologic study of coronary heart disease initiated in 1965. An index of daily physical activity and a metabolic equivalent of heaviest activity were estimated from each individual history. Rural men had higher mean levels of overall activity as well as higher levels of heavy activity than urban men. An $\text{8}\text{1}\text{4}$ year follow-up study for coronary heart disease other than angina pectoris was analyzed for relationships with physical activity. Significant inverse associations were found for both urban and rural men. Metabolic equivalent of heaviest activity showed similar results. Although the physical activity index was inversely associated with most known coronary risk factors, multivariate analyses indicated that a significant independent inverse relationship existed with the incidence of coronary heart disease. In Puerto Rico, increased physical activity appears to be a separate protective factor against heart attacks.