Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

To better define the mechanisms of blood pressure control in states of catecholamine excess, we infused norepinephrine for 28 days using subcutaneously implanted osmotic pumps in dogs previously instrumented for monitoring left ventricular dynamics and cardiac output. Plasma norepinephrine rose from 238 +/- 27 to 4346 +/- 952 pg/ml at 21 days, while epinephrine and dopamine levels did not change. Heart rate fell from 85 +/- 4 to 63 +/- 6 beats/min, while arterial pressure was unchanged from baseline. Total peripheral resistance rose 0.011 +/- 0.003 mm Hg/ml/min from a control value of 0.029 +/- 0.002 mm Hg/ml/min, and cardiac output decreased 1093 +/- 292 ml/min from a baseline level of 3575 +/- 156 ml/min. Since stroke volume did not change, the maintenance of arterial pressure is related to decreases in cardiac output secondary to bradycardia. Buffering mechanisms are responsible for maintenance of systemic arterial pressure because hexamethonium and atropine caused hypertension. Although left ventricular end-diastolic pressure, end-diastolic diameter, shortening, rate of change of pressure, velocity of myocardial shortening, cardiac work, stroke work, and the double product did not change significantly during the study, postmortem examination demonstrated biventricular hypertrophy. Thus, despite markedly elevated catecholamine levels and no elevation of systemic arterial pressure, myocardial hypertrophy developed. These studies lend support to the hypothesis that norepinephrine may be a direct myocardial tropic hormone and suggest that intense activation of reflex buffering mechanisms maintains blood pressure in the normal range during chronic catecholamine infusion.

Clinical use of oral verapamil in chronic and paroxysmal atrial fibrillation.

We evaluated the effectiveness of oral verapamil therapy for control of ventricular rate in digitalized patients with atrial fibrillation (AF) with three clinical problems: chronic AF with rapid rate at rest (four patients), chronic AF with accelerated rate during modest exercise (five patients), and rapid rates during paroxysmal AF (four patients). Patients in the first two categories were evaluated both by open-label dosage titration and by a randomized, double-blind, cross-over protocol. In chronic AF with rapid rate of rest, there was a significant reduction in resting heart rate (from 125 +/- 7 to 87 +/- 14, P less than 0.01) and in peak exercise heart rate (from 162 +/- 33 to 126 +/- 25, P less than 0.01). In chronic AF with rapid rate during exercise, there was also a significant decrease in resting heart rate (from 90 +/- 7 to 66 +/- 4, P less than 0.01) and in peak exercise heart rate (from 126 +/- 19 to 101 +/- 15, P less than 0.01). These effects continued during longterm follow-up of one to 12 months (mean seven months). In patients with paroxysmal AF, verapamil slowed the ventricular response from 16- +/- 24 to 72 +/- 4 P less than 0.01) with only some amelioration of symptoms. Therapy was well tolerated despite a high prevalence (seven of 13 patients) of radiographic cardiomegaly (cardiothoracic ratio greater than 0.55). We conclude that verapamil is a safe and useful drug for control of ventricular rate in digitalized patients with chronic and paroxysmal AF.

Effect of lactose, copper and iron on manganese retention and tissue distribution in rats fed dextrose-casein diets.

The effect of iron, lactose and copper on manganese retention was studied in rats fed two diets. Thirty-six male albino rats (75 to 100 g) were allotted to six groups of six rats each. Three groups received a purified manganese-free dextrose-casein diet, and three groups received the same purified diet with 17% lactose added at the expense of dextrose. One group fed each of the above diets received either a manganese-free mineral mixture, the mineral mixture with 5 ppm supplemental Cu or the same mineral mixture with Fe removed. After 7 days on the diets, each rat was given, by gavage, 10 muCi of 54Mn activity as 54MnCl2 in a sodium acetate buffer. On the third day after dosing, the rats were sacrificed and samples of liver, kidneys, semitendinosus muscle, spleen and tibia were taken for stable and radioactive manganese analysis. Lactose added to the purified diet depressed 54Mn retention in all tissues studied. Lactose addition also decreased specific activities of the livers and kidneys but tended to increase stable manganese values. Copper apparently had little direct effect on 54Mn retention but tended to reduce the effect of lactose on 54Mn retention. Omission of Fe greatly increased 54Mn retention values in all tissues studied with or without added lactose. Fe omission also significantly increased the specific activities and stable Mn values of livers and the specific activity of kidneys. The results indicate that low dietary Fe may be a contributing factor to the increased manganese retention observed in this study and a previous study.

Mitral valve prolapse: a marker for anxiety or overlapping phenomenon?

In symptomatic mitral valve prolapse patients (MVP): (1) the frequency and nature of symptoms were analyzed (n = 313); (2) metabolic studies were performed (n = 20), and (3) the response to isoproterenol infusions were studied (n = 16). Chest pain is more often the initial symptom in men; palpitations are more common initially in women. Fatigue, palpitations, dyspnea and arrhythmias are more frequent in women. Chest pain and neurologic events occur with the same frequency in both sexes. Women have more symptoms than men. MVP patients have normal thyroid function tests, normal plasma cortisol, normal diurnal variation of cortisol and normal 24-hour 17-ketosteroids and 17-hydroxycortico-steroids excretion. They have a normal response to oral glucose but higher glucose and insulin levels than controls. MVP patients have increased 24-hour urinary catecholamine excretion. Isoproterenol infusions produce symptoms in a dose-related fashion in MVP patients but not in controls. Isoproterenol infusion-related symptoms included chest pain (7), extreme fatigue (6), dyspnea (6), dizziness (4), numbness (2), panic attacks (2). Isoproterenol infusions produced a greater increase in heart rate in MVP patients compared to controls. Thus, MVP patients have increased catecholamines and hyperresponse to isoproterenol infusion which indicates that their symptoms may be catecholamine related or mediated. The complex relationships of MVP symptoms are not clear; the coexistence of anxiety states and MVP is one explanation; another equally plausible explanation is that MVP may be a specific marker for the symptom complex.

Synthesis and determination of manganese carbonate and manganese-54 carbonate.

A method was developed by which radioactive manganese, manganese-54 carbonate (with a high specific activity), could be produced. This was accomplished by reacting manganese-54 chloride, manganese chloride tetrahydrate, and sodium bicarbonate. This reaction produced manganese-54 carbonate (specific activity .35 mCi/mg manganese mixed with stable manganese. The purity of the manganese carbonate (manganese-54 carbonate) was determined by the use of x-ray diffraction methods. One method compared "d" spacings (distance in angstroms between lattice planes of a crystal) with standard and index values for pure manganese carbonate. Another method compared x-ray diffractograms of the synthesized product with standard manganese carbonate. By both methods all material was the carbonate form of manganese (manganese-54 carbonate).

Dynamic contrast-enhanced MR imaging of the pituitary gland with fast spin-echo technique.

Preliminary work has demonstrated that dynamic contrast material-enhanced magnetic resonance imaging improves the detection sensitivity for pituitary microadenomas. The authors present a new method of obtaining dynamic contrast-enhanced pituitary images with a short TR/TE fast spin-echo technique. This approach allows acquisition of contrast-enhanced spin-echo images with high temporal and spatial resolution. The new technique is applied in a small group of patients and control subjects.

Effect of a purified or corn-skim milk diet on retention and tissue distribution of manganese-54 in calves.

Calves were fed a corn-skim milk or a purified diet to determine if the large differences in manganese metabolism in rats fed such diets also occurred in ruminating calves. The calf purified diet was similar to the rat purified diet but with potassium bicarbonate and sodium bicarbonate added as buffers to be suitable for ruminating calves. In contrast to the huge differences in rats, retention of manganese-54 was the same in calves fed the corn-skim milk diet as in calves fed the purified diet. It is unlikely that the minor differences in the diets caused such large differences in effects between calves and rats. A likely reason for the difference is the functional rumen in the calf. The active rumen may metabolize ingredient(s) that affect manganese absorption in the rat and, therefore, would not be in the small intestine to affect absorption by the calf.

High resolution 3D imaging of the inner ear with a modified fast spin-echo pulse sequence.

A fast spin-echo pulse sequence is described that produces high resolution images of the inner ear without susceptibility artifacts. It uses thin overlapping slices that can be reformatted in multiple projections to provide a view of the 3D geometry of inner ear structures, such as the cochlea, vestibule, semicircular canals, and internal auditory canal. It has proven useful in screening adults for the presence of acoustic schwannoma and in identifying structural congenital lesions in children with sensorineural hearing loss.

Global myocardial hypertrophy in conscious dogs with chronic elevation of plasma norepinephrine levels.

Chronically elevated plasma norepinephrine is associated with many disease states in which myocardial hypertrophy is also found, yet whether the hypertrophy results from the hemodynamic actions of catecholamines or a trophic effect is still unknown. The goal of our study was to determine the extent of hypertrophy following 28 days of norepinephrine infusion and the role of altered hemodynamics as the stimulus for the hypertrophy in conscious dogs. In a retrospective study gross cardiac weights were examined in 25 control instrumented dogs (controls) and in 41 instrumented dogs with elevated norepinephrine (NE). In the NE dogs LV (94 +/- 2.8 g), septum (33 +/- 1.5 g) and total heart weights (172 +/- 4.5 g) were greater than in controls (85 +/- 5.0, 31 +/- 1.9, and 158 +/- 9.0 g, respectively). The LV (3.95 +/- 0.10 g/kg), RV (1.91 +/- 0.06), septum (1.38 +/- 0.06) and total weight (7.23 +/- 0.15) to body weight ratios were also significantly greater (3.32 +/- 0.12, 1.73 +/- 0.08, 1.24 +/- 0.06, and 6.28 +/- 0.23 g/kg). The dry/wet weight ratios were not different in the two groups. After cutting the hearts into 1 cm rings, the planimetered area of each ring showed that the wall thickness increased at all levels, e.g. at the base by 25 +/- 3.2%. The chamber internal diameter was significantly increased only near the apex in the NE dogs making the heart more cylindrical in shape. There was no obvious sign of fibrosis in any layer of the myocardium. In physiologic studies, no index of contractility was altered including: LV dP/dt, LV dD/dt, shortening, LV dWT/dt and there was also no change in preload. Heart rate was significantly reduced throughout the 28 days of study. Cardiac output was reduced and there were no significant changes in cardiac work. Thus in these dogs NE caused a 19% and 10% increase in LV and RV to body weight ratios, respectively, without any obvious hemodynamic stimulus.