Effect of Aminophylline on Urinary Excretion of Epinephrine and Norepinephrine in Man

Atuk, Nuzhet O.; Blaydes, M. Cary; Westervelt, Frederic B.; Wood, J. Edwin

doi:10.1161/01.cir.35.4.745

Cited by 96 publications

(20 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The findings are consistent with reports that theophylline increased circulating levels of catecholamines. 10,11,13 The increases in plasma catecholamine concentrations correlated with the doserelated increases in HR observed during their study, supporting the hypothesis that the cardiovascular effects of theophylline may be mediated in part by the beta-adrenergic system.…”

Section: Discussionsupporting

confidence: 61%

“…13 Tachycardia during theophylline intoxication occurs by a direct effect of theophylline on the sinus node, an increase in sympathetic nervous system activity, or an increase in catecholamines. 10,13 In this study, plasma concentrations of catecholamines increased from baseline values after administration of aminophylline. The findings are consistent with reports that theophylline increased circulating levels of catecholamines.…”

Section: Discussionmentioning

confidence: 48%

“…[7][8][9] Theophylline toxicity induces severe tachyarrhythmias in humans [10][11][12] and in an animal model. 13 The purpose of this study was to examine the effect of landiolol on hemodynamics during acute theophylline intoxication in halothane-anesthetized dogs.…”

Section: Laboratory Investigationsmentioning

confidence: 99%

See 2 more Smart Citations

Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs

Takahashi

Fujii

Hoshi

et al. 2000

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

Purpose: To examine the effect of landiolol (ONO-1101), a new ultra-short acting, highly selective beta 1 blocker, on hemodynamic response to acute theophylline intoxication in anesthetized dogs.Methods: Thirty-four dogs were studied during halothane anesthesia. Aminophylline (50 mg·kg -1 over 20 min followed by infusion at 1.75 mg·kg -1 ·hr -1 ) was administered as a model of acute theophylline intoxication. Dogs were randomly enrolled into four landiolol groups (0, 1, 10, 100 µg·kg -1 ·min -1 ) to treat tachyarrhythmias. Hemodynamic variables, heart rate (HR), systemic blood pressure (SBP), pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output (CO) were measured along with plasma concentrations of theophylline, epinephrine, and norepinephrine. Results: After 60 min, plasma concentration of theophylline reached 46.6 ± 4.0 (mean ± SD) µg·ml -1 , HR increased from 129 ± 21 to 193 ± 27 bpm (P < 0.0001) and CO increased from 1.6 ± 0.5 l·min -1 to 2.1 ± 0.4 l·min -1 (P < 0.0001), whereas SBP decreased from 139 ± 25 to 121 ± 25 mm Hg (P < 0.0001), with decreasing systemic vascular resistance. After intoxication, plasma epinephrine concentration increased from 125 ± 112 to 325 ± 239 pg·ml -1 (P < 0.0001), and norepinephrine concentration from 103 ± 61 to 133 ± 61 pg·ml -1 (P < 0.0011). Landiolol 10 µg·kg -1 ·min -1 decreased HR to pre-intoxication level, whereas HR returned to the intoxication baseline by 30 min after cessation of landiolol infusion. Conclusions: Landiolol controlled tachyarrhythmias associated with theophylline toxicity. The optimal effective dose of landiolol was 10 µg·kg -1 ·min -1 .Objectif : Examiner l'effet du landiolol (ONO-1101), nouveau bloqueur beta 1 hypersélectif à action ultrabrève, sur la réponse hémodynamique de l'intoxication aiguë à la théophylline chez des chiens anesthésiés. Méthode : L'étude a porté sur 34 chiens anesthésiés à l'halothane. L'aminophylline (50 mg·kg -1 pendant 20 min, suivi d'une perfusion à 1,75 mg·kg -1 ·hr -1 ) a été administrée pour provoquer l'intoxication aiguë à la théophylline. Les chiens, répartis au hasard en quatre groupes, ont reçu différentes doses de landiolol (0, 1, 10, 100 µg·kg -1 ·min -1 ) pour traiter la tachyarythmie. On a mesuré : la fréquence cardiaque (FC), la pression sanguine systémique (PSS), la pression artérielle pulmonaire, la pression artérielle pulmonaire bloquée et le débit cardiaque (DC) de même que les concentrations plasmatiques de théophylline, d'épinéphrine et de norépinéphrine. Résultats : Après 60 min, la concentration plasmatique de théophylline était de 46,6 ± 4,0 (moyenne ± écart type) µg·ml -1 , la FC avait augmenté de 129 ± 21 à 193 ± 27 bpm (P < 0,0001) et le DC était passée de 1,6 ± 0,5 l·min -1 à 2,1 ± 0,4 l·min -1 (P < 0,0001), tandis que la PSG avait baissé de 139 ± 25 à 121 ± 25 mm Hg (P < 0,0001) et que la résistance vasculaire générale diminuait. Après l'intoxication, la concentration plasmatique d'épinéphrine a augmenté de 125 ± 112 à 325 ± 239 pg·ml -1 (P < 0,0001), et la concentratio...

show abstract

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 48%

See 1 more Smart Citation

Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs

Takahashi

Fujii

Hoshi

et al. 2000

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

show abstract

“…Failure to recover normal cardiac function after cardiopulmonary bypass correlates well with the inability to resynthesize normal levels of ATP. 14 7,8 However, this may be a consequence of the loss of ATP precursors rather than…”

mentioning

confidence: 99%

Effect of intravenous aminophylline on plasma levels of catecholamines and related cardiovascular and metabolic responses in man.

Vestal¹,

Eiriksson²,

Musser³

et al. 1983

Circulation

141

View full text Add to dashboard Cite

SUMMARY Theophylline is thought to act by inhibiting the activity of phosphodiesterase, with a resultant increase in intracellular cyclic AMP. However, this concept is largely based on in vitro studies using concentrations of theophylline which greatly exceed therapeutic plasma concentrations. To investigate the relationship of the cardiovascular and metabolic effects of theophylline to activation of the sympathetic nervous system, i.v. aminophylline was administered to six healthy males under basal conditions. Each subject received four infusions. Mean theophylline concentrations (±+ SEM) of 4.5 + 0.2, 10.0 0.5, 14.0 + 0.5 and 20.0 + 1.2 ,ug/ml were achieved. Plasma epinephrine increased 262% (from 29 4 to 105 14 pg/ml, p < 0.01) and plasma norepinephrine increased 64% (from 190 1 18 to 312 51 pglml, p < 0.05) during the high-dose infusion. The increases in circulating catecholamines were dose-related (p < 0.001 by analysis of variance). Dose-related increases in heart rate, systolic blood pressure, plasma glucose, free fatty acids and insulin were also observed (p < 0.001 by analysis of variance). Although the duration of total electromechanical systole (QS2) and left ventricular ejection time adjusted for heart rate fell during the aminophylline infusions, this positive inotropic response was not influenced by dose, except possibly the high dose. Echocardiographic ejection fraction was not changed by the aminophylline infusions. We conclude that the acute cardiovascular and metabolic effects of theophylline may be mediated in part by stimulation of the sympathetic nervous system. AMINOPHYLLINE (theophylline ethylenediamine) is a methylxanthine derivative that is widely used in the treatment of cardiovascular and respiratory disease. Although ethylenediamine has been implicated in allergic reactions to aminophylline, it is otherwise thought to be therapeutically inactive. Theophylline and other methylxanthines are known to exert a variety of important physiologic and biochemical effects. ' Although the dose-response relationship between plasma concentrations of theophylline and improvement of pulmonary function during bronchospasm is well established,2' I a similar relationship for its cardiovascular and metabolic effects has only recently been examined in human studies." Despite the evidence that the acute administration of methylxanthine derivatives stimulates the release of epinephrine and norepinephrine from the sympathoadrenal system in man,7' 8 the extent to which this response may be dose-or concentration-dependent has only been studied in an in vitro system, the isolated perfused adrenal gland.9' 10 Epinephrine and norepinephrine are known to have chronotropic and inotropic effects on the heart, which, together with vasoconstrictor effects, lead to an increase

show abstract

“…Cross-tolerance developed to isoprenaline when the guinea-pig was pretreated with adrenaline and also to aminophylline when the animals were pretreated with isoprenaline. The aminophylline experiments may not indicate whether tolerance is specific and/or non-specific, since aminophylline can be regarded as an indirectly acting sympathomimetic amine because it causes an increase in the release of endogenous catecholamines into the blood circulation (Atuck, Blaydes, Westervelt & Wood, 1967;Westfall & Fleming, 1968;Peach, 1972;Wooten, Thoa, Koplin & Axelrod, 1973 metic amines may also act in a way similar to aminophylline, since adrenaline inhibits phosphodiesterase activity (Hitchcock, 1973). Conolly et al (1971 reported that in guineapigs, the mortality from histamine-induced bronchospasm was higher in groups which had been pretreated with sympathomimetic amines than in groups which had been pretreated with saline.…”

Section: Cross-tolerance Studiesmentioning

confidence: 99%

TOLERANCE TO SYMPATHOMIMETIC BRONCHODILATORS IN GUINEA‐PIG ISOLATED LUNGS FOLLOWING CHRONIC ADMINISTRATION in vivo

Benoy

Elfellah

Schneider

et al. 1975

British J Pharmacology

View full text Add to dashboard Cite

Pretreatment of the guinea‐pig subcutaneously three times daily with either 5 μg/kg isoprenaline or adrenaline reduced the response of the isolated perfused histamine‐constricted lung when challenged with either the same or a different sympathomimetic bronchodilator. The longer the animals were pretreated and the higher the dose of bronchodilator the greater was the degree of tolerance developed. Tolerance was developed to aminophylline in the same preparation when the guinea‐pig had been pretreated with aminophylline or isoprenaline. Cross‐tolerance also developed to adrenaline when the guinea‐pig had been pretreated with aminophylline. Tolerance was still persistent in guinea‐pigs one and two weeks after pretreatment three times daily with either isoprenaline or adrenaline (5 μg/kg s.c.) for seven days in the same preparation. Only after three weeks was the tolerance diminished. These results suggest that asthmatic patients who use bronchodilators excessively may become refractory to the bronchodilator effect of these drugs. They also support the hypothesis that induced cross‐resistance to endogenous sympathetic stimulation could lead to a deterioration of the asthmatic state in patients using the sympathomimetic bronchodilators and that this may explain the increase in asthma mortality rate. A mechanism of tolerance to sympathomimetic bronchodilators is postulated.

show abstract

Effect of Aminophylline on Urinary Excretion of Epinephrine and Norepinephrine in Man

Cited by 96 publications

References 26 publications

Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs

Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs

Effect of intravenous aminophylline on plasma levels of catecholamines and related cardiovascular and metabolic responses in man.

TOLERANCE TO SYMPATHOMIMETIC BRONCHODILATORS IN GUINEA‐PIG ISOLATED LUNGS FOLLOWING CHRONIC ADMINISTRATION in vivo

Contact Info

Product

Resources

About