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Biomedical subjects

R E Rangno

Publications and source records attributed to R E Rangno.

At least 19 recordsLinked to original sources
PubMed1991

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↗
PubMed1986

Leukocytosis of exercise: role of cardiac output and catecholamines.

The effect of propranolol (5 mg iv) on the leukocytosis of exercise was studied in seven normal young males. Leukocyte counts, plasma norepinephrine (NE), epinephrine (E), and cardiac output were measured at rest and in the steady state of several submaximal work loads when subjects exercised on a cycle ergometer. The results in control experiments were compared with those obtained on a different day with propranolol. Propranolol decreased heart rate at all work loads (P less than 0.001) but had no effect on the increase in cardiac output at increasing work loads. Plasma NE and E levels were similar at rest and in exercise in control and propranolol studies. There was no effect of propranolol on the increase in leukocyte counts with increasing work loads. Although propranolol did not affect the increase in total leukocyte count, the increase in lymphocyte count at higher work loads was less with propranolol. We conclude that the demargination of leukocytes from the pulmonary circulation in exercise is probably a mechanical effect of the increase in cardiac output. However, we have not excluded a contribution from a humoral event that would decrease the adherence of leukocytes to endothelium during exercise. The smaller increase in lymphocytes at higher work loads in the presence of propranolol suggests that catecholamines affect the lymphocyte count over and above their effect on cardiac output.

Adult↗
PubMed1982

Comparison of withdrawal phenomena after propranolol, metoprolol, and pindolol.

Three groups of hypertensive patients were studied after they had received one of the three pharmacologically different beta blockers for at least 1 month: pindolol, 10 mg twice a day (n = 7), propranolol median dose, 80 mg three times a day (n = 9), or metoprolol, 150 mg (twice a day (n = 8). After abrupt withdrawal of drug and replacement with placebo, we measured the following on day 0 and approximately every 2 days up to 3 weeks; beta-adrenergic sensitivity (BAS) by the chronotropic dose of isoproterenol to increase heart rate by 25 bpm (CD25), resting heart rate and blood pressure, and symptoms. All values are medians. On day 0, beta blockade was evident by increased CD25 values of 618 micrograms for pindolol, 57 micrograms for propranolol, and 10 micrograms for metoprolol as compared to 2.8, 2.4, and 3.0 microgram, respectively, at days 14 to 21, which were considered the ultimate baseline. After pindolol on day 0, the CD25 slowly decreased to, but never below, baseline by days 8 to 21. In contrast, after propranolol on day 0, the CD25 decreased significantly two- to fivefold below baseline from days 4 to 14 (BAS) and after metoprolol two- to threefold below baseline from days 2 to 8. After pindolol, heart rate and blood pressure gradually returned to, but not above, ultimate baseline. In contrast, during the period of BAS there was a significant overshoot of heart rate in eight patients after metoprolol (day 0 = 61, peak = 88, baseline = 74) but not after propranolol, while a significant overshoot of blood pressure occurred in six of nine patients after propranolol (day 0 = 140/87, peak = 157/95, baseline = 140/89) but not after metoprolol. Withdrawal symptoms of headache, palpitations, and tremor occurred in one of seven patients after pindolol, six of nine after propranolol, and three of eight after metoprolol. The degree and duration of beta blockade appeared related to drug potency. Withdrawal phenomena occurred after propranolol and metoprolol but not after pindolol.

Adult↗
PubMed1982

Prevention of propranolol withdrawal mechanism by prolonged small dose propranolol schedule.

Abrupt withdrawal of propranolol may be followed by a "propranolol withdrawal syndrome "due, at least in part, to enhanced beta adrenergic sensitivity. Tapering propranolol dosage is frequently used in the hope of preventing adverse withdrawal events but the success of such a maneuver has not been shown. The rationale for the dose tapering schedule in this study was based on earlier observations after abrupt withdrawal of propranolol. Nine hypertensive patients were gradually withdrawn from long-term propranolol therapy, either by serial dose reduction for 6 to 9 days (n = 3) or by reduction to a prolonged small dose (30 mg daily) for 2 weeks before complete withdrawal (n = 6). During dose reduction of propranolol and for 2 additional weeks of placebo therapy, serial measurements were made of cardiac sensitivity to isoproterenol, heart rate at rest, blood pressure, plasma catecholamines, serum thyroxine (T4) and triiodothyronine (T3) and symptoms. Serial dose reduction decreased but did not prevent cardiac hypersensitivity in two of three patients. The prolonged small dose therapy largely prevented cardiac hypersensitivity and overshoot in heart rate, blood pressure and plasma catecholamines and symptoms. Serum T4 decreased significantly and T3 tended to increase during and after prolonged small dose treatment. These results indicate that prolonged administration of small dose propranolol before complete withdrawal in hypertensive patients prevents enhanced cardiac beta adrenergic sensitivity and other adverse events.

Adult↗
PubMed1982

Metoprolol withdrawal phenomena: mechanism and prevention.

Eight patients taking metoprolol (300 mg/day) for essential hypertension were studied after abrupt withdrawal and placebo replacement of the drug. A 52% average rebound increase in cardiac chronotropic sensitivity to isoproterenol and 15% rebound rise in resting heart rate occurred in all patients between 2 to 8 days after metoprolol withdrawal (P less than 0.05). Holter monitoring showed no associated arrhythmia. A transient increase in blood pressure occurred in one patient and withdrawal-like symptoms were noted in three patients. There were no meaningful changes in plasma norepinephrine, epinephrine, thyroxine, or triiodothyronine. Seven of the eight patients were again studied serially after the same metoprolol dosing, during a prolonged low-dose withdrawal schedule (50 mg/day for 10 days) and during placebo. Prolonged low dose before complete metoprolol withdrawal decreased but did not completely prevent the changes observed after abrupt withdrawal. The observed rebound of cardiac beta-adrenergic sensitivity may have application to the mechanism and prevention of the beta-blocker syndrome in patients with angina.

Adult↗
PubMed1982

Cardiac hyper- and hyporesponsiveness after pindolol withdrawal.

Abrupt withdrawal of some beta-adrenergic blockers has resulted in clinical syndromes suggestive of adrenergic hypersensitivity that may be due to an adaptive increase in cardiac beta-receptor responsiveness. it was postulated that the partial agonist activity of pindolol might limit enhanced responsiveness of cardiac beta receptors and prevent or diminish withdrawal manifestations. Pindolol was given to 10 hypertensive patients in doses of 10 mg b.i.d. for at least 4 wk, then abruptly replaced with placebo for 20 days. Cardiac chronotropic responsiveness to isoproterenol was decreased on pindolol and gradually returned to normal over 10 to 20 days with no evidence of enhanced responsiveness. In contrast, both resting and exercise heart rate showed rebound increase in responsiveness between the second to sixth day after pindolol (P less than 0.05). Resting and exercise blood pressures gradually rose to stable values without rebound. Plasma norepinephrine and epinephrine and serum thyroxine and triiodothyronine did not change. These data show that abrupt withdrawal of pindolol after long-term dosing leads to transient cardiac hyperresponsiveness of resting and exercise heart rate at the same time as persistent cardiac hyporesponsiveness to isoproterenol. These opposite effects of pindolol on subsets of cardiac beta-adrenergic chronotropic receptors.

Adult↗
PubMed1982

Effect of ethanol ingestion on outcome of drug overdose.

It was traditionally assumed that ethanol, as part of an intentional drug overdose, will increase morbidity and mortality. The authors prospectively studied the effect of ethanol on the outcome of intentional drug overdose in 468 adults, 196 of whom required hospital admission. Ethanol was detected in significantly fewer patients who required admission. Ethanol ingestion was not related to coma, impaired vital signs or mortality. Indeed, the duration of coma was significantly shorter in patients in whom ethanol was detected, but this group had a lesser incidence of multiple drug and nonbarbiturate hypnotic ingestion and a greater incidence of chronic ethanol use. Thus, it seems that ethanol is not associated with a worse clinical course if the drug overdose patient reaches medical care before an irreversible event.

Adolescent↗
PubMed1982

Comparison of withdrawal phenomena after propranolol, metoprolol and pindolol.

1 After abrupt propranolol withdrawal a rebound increase in cardiac sensitivity to isoprenaline occurred in 9/9 patients and persisted up to 14 days. A mild brief rebound in resting heart rate occurred in 4/9 patients and a rebound in blood pressure occurred in 6/9 patients. These withdrawal phenomena were prevented by gradual withdrawal on a prolonged small dose of propranolol. 2 After abrupt metoprolol withdrawal a rebound increase in cardiac sensitivity to isoprenaline occurred in 8/8 patients but had resolved by 8 days. A marked persistent rebound in resting heart rate occurred in 8/8 patients while a small brief rebound in blood pressure occurred in only one patient. These withdrawal phenomena were largely prevented by gradual withdrawal on a prolonged small dose of metoprolol. 3 After abrupt pindolol withdrawal there was no rebound in isoprenaline sensitivity but a mild brief rebound in resting heart rate occurred in 9/10 patients. There was no rebound in blood pressure. 4 The type, magnitude and frequency of withdrawal phenomena after various beta-adrenergic receptor blockers probably reflects substantial differences in their basic pharmacological characteristics. 5 Caution must be exercised when withdrawing any patient from any beta-adrenoceptor blocker since an adverse cardiac event is unpredictable.

Adrenergic beta-Antagonists↗
PubMed1981

Ethanol 'dose-dependent' elimination: Michaelis-Menten v classical kinetic analysis.

1 To compare classical linear regression techniques and a Michaelis-Menten elimination model eight normal human volunteers each received three intravenous doses (0.375, 0.5, and 0.75 g/kg) of ethanol and four of the subjects each received four oral doses (0.5, 0.65, 0.95, 1.25 g/kg) of ethanol. 2 Computerized analysis of the time-plasma concentration profiles using a two-compartment Michaelis-Menton elimination model yielded a median absorption constant of 1.29 h-1; volume of distribution of 0.47 l/kg; Vmax of 0.12 g h-1 kg-1; and Km of 0.03 g/l. Classical techniques resulted in a slope of 0.20 g l-1 h-1, volume of distribution of 0.55 l/kg, and a B60 of 0.11 g h-1 kg-1. 3 Transient post-prandial decreases in elimination slope occurred at higher oral doses. A trend of increasing slope with increasing oral dose was seen at concentrations well above the Km. Time to sobriety (0.8 g/l) increased nonlinearly with increasing peak concentration. 4 Maximal ethanol elimination rates are determined equally well by the two techniques. Classical analyses overestimate the volume of distribution of ethanol by 17%. Neither technique helps explain the post-prandial changes in slope or increasing slope with dose at high concentrations.

Adult↗
PubMed1980

Nonspecific arousal with noloxone.

The use of naloxone, the first narcotic antagonist devoid of agonist properties, has become the standard way of treating narcotic-induced coma and respiratory depression. This report concerns a patient in whom a narcotic effect was unlikely, but who nevetheless showed arousal after naloxone administration.

Aged↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1977

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↗