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Biomedical subjects

R E Rangno

Publications and source records attributed to R E Rangno.

11 recordsLinked to original sources

Catecholamine responses to histamine infusion in man.

To evaluate the effects of histamine-induced hypotension on plasma catecholamine levels, eight normal men, aged 20 to 40 years, were infused with incremental doses of histamine starting at 0.2 microgram/kg/min at a 30 degree tilt position with monitoring of blood pressure (BP) and heart rate. Histamine dosage was increased every 5 minutes by 0.1 to 0.2 microgram/kg/min until mean BP fell greater than 15 mm Hg or a dosage of 1.6 micrograms/kg/min was reached. Plasma catecholamine samples were taken between the fourth and fifth minute of each histamine dosage. Identical measurements were made during nitroglycerin-induced hypotension in these subjects. Histamine produced threefold greater increases in heart rate and plasma norepinephrine (NE) levels than did nitroglycerin for comparable decreases in BP. Although NE levels increased twofold to fivefold from baseline with histamine infusion, epinephrine levels increased minimally at the highest doses or not at all. Our data demonstrate that histamine selectively releases NE from adrenergic nerve terminals without significant adrenal catecholamine release. We suggest that neural NE release plays an important role in the cardiac effects of histamine.

Adult

Antihypertensive efficacy of propranolol given twice daily.

The therapeutic efficacy of propranolol in four and two daily doses was compared in 63 treated hypertensive patients in a multicentre trial. After 3 months of a stable diastolic blood pressure while receiving propranolol four times a day the patients were switched to a twice-a-day regimen, the drug being given at 8 am and 8 pm, with the same total daily dose, for 3 more months. Blood pressures and heart rates were measured at 8 am, 12 noon, 4 pm and 8 pm at 4-week intervals. There were no significant changes in mean blood pressure after the change to the twice-a-day regimen, although some patients reported new side effects. Compliance appeared to be unaffected.

Adolescent

Mechanism of propranolol withdrawal phenomena.

Nine patients on chronic treatment with propranolol for essential hypertension for 3 months or longer were studied after abrupt discontinuation of the drug. Each patient demonstrated transient supersensitivity to the chronotropic effects of isoproterenol, beginning 2--6 days (median 4 days) after propranolol withdrawal, lasting for 3--13 days (median 6 days), with the maximum sensitivity on day 6. A significantly lower dose of isoproterenol was necessary to increase heart rate 25 beats/min on day 6 (median dose 1.2 microgram, range 0.3--3.4 microgram) compared with after day 14, when sensitivity had stabilized (median dose 2.3 microgram, range 1.4--7.6 microgram). Six patients had transient symptoms (headache, chest pain, palpitations and sweating) after abrupt propranolol withdrawal, coinciding with supersensitivity to isoproterenol in five. Transient increases in plasma catecholamines and blood pressures and sustained increases in heart rate occurred during the period of isoproterenol supersensitivity in most patients, and may have contributed to symptoms noted. The delayed onset and potentially long duration of beta-adrenergic supersensitivity after abrupt propranolol withdrawal have important clinical implications.

Adult

Theophylline disposition in patients with hepatic cirrhosis.

To determine the role of liver dysfunction in theophylline toxicity, we administered single intravenous doses of the drug to nine patients with cirrhosis and observed its disposition over a period of 24 to 48 hours. As compared to 19 normal subjects, these patients had a prolonged plasma half-life (mean, 25.6 vs. 6.7 hours) and a decreased plasma clearance (mean, 0.042 vs. 0.062 liter[kg-1]hr-1). Volumes of distribution of theophylline in the cirrhotic patients (central-compartment volume of 0.330, and steady-state volume of distribution of 0.785 liter per kilogram) did not substantially differ from normal (0.246 and 0.508 respectively). Plasma theophylline binding in three patients with cirrhosis averaged 36.8 per cent as compared to 52.6 per cent in four normal subjects. There was no correlation between any laboratory test of liver function and the plasma theophylline half-life, except for serum albumin (r = 0.92, P less than 0.001). The variable capacity to eliminate theophylline precludes the use of usual maintenance dose schedules for bronchodilation in cirrhosis.

Adult

Theophylline kinetics in acute pulmonary edema.

Nine patients with acute cardiogenic pulmonary edema were given theophylline intravenously, and its disposition was observed over the next 24 hr. Compared to that in 19 normal subjects, these patients had prolonged plasma half-lifes (mean, 22.9 from 6.7 hr) and decreased plasma clearances of theophylline (mean, 0.041 from 0.062 L [kg-1] hr-1). The intersubject variation in these parameters was 20-fold in patients with pulmonary edema and 4-fold in normal subjects. Since the peak plasma concentrations attained and the apparent volumes of distribution were not different in the two groups, a suitable initial dose can be calculated. A loading dose of 4.5 to 5 mg/kg theophylline (6 mg/kg aminophylline) given over 20 min appears safe. Because of the great variability in the plasma clearance of this drug in patients with heart failure, plasma concentrations and toxicity would be unpredictable after repeated doses or constant infusions.

Acute Disease

Modified colorimetric method for procainamide in plasma.

We describe a modified colorimetric method for determining procainamide in plasma by use of a diazotization and coupling reaction with N-(1-naphthyl)-ethylenediamine dihydrochloride (Marshall's reagent). The sensitivity of the assay is increased twofold over the originally reported colorimetric method, and the lower limit of detection for the assay of a 1.0-ml plasma sample has been decreased to 0.5 mg/liter.

Colorimetry

Plasma theophylline concentrations measured by high-pressure liquid chromatography.

We present a specific, sensitive high-pressure liquid-chromatographic assay for theophylline in plasma. Only 0.5 ml of plasma is required for each determination, and the lower limit of detection by this method is 0.1 mg/liter. Other xanthines and their metabolites do not interfere. This method is suitable for use in studying the pharmacokinetics of this drug in infants and children, from whom only small volumes of blood are available.

Aminophylline