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PubMed1989

Aminophylline does not attenuate histamine-induced airway constriction during halothane anesthesia.

The effects of aminophylline on the release of endogenous catecholamines and on airway reactivity to aerosol histamine challenge were evaluated during halothane and thiopental/fentanyl anesthesia in basenji-greyhound dogs. Responses to histamine aerosol challenge (0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/ml) were measured during six conditions: 1) thiopental/fentanyl anesthesia (control), 2) thiopental/fentanyl with aminophylline infusion, 3) halothane anesthesia (1.5 MAC), 4) halothane anesthesia with aminophylline infusion, 5) thiopental/fentanyl anesthesia after pretreatment with iv propranolol, and 6) thiopental/fentanyl anesthesia with aminophylline infusion after pretreatment with iv propranolol. Prior to aerosol challenge baseline pulmonary resistance (RL) did not differ in the six groups. Aminophylline significantly attenuated the pulmonary response to histamine and increased catecholamine concentrations during thiopental/fentanyl anesthesia. Although halothane itself significantly attenuated the pulmonary response to histamine, the administration of aminophylline during halothane anesthesia produced no additional protective effect and no increases in catecholamines were noted. Moreover, no protective effect was seen after aminophylline administration during thiopental/fentanyl anesthesia in the same dogs pretreated with propranolol. These data suggest that the protective effect of aminophylline on histamine reactivity results from release of endogenous catecholamines and that the use of aminophylline during halothane anesthesia, which blocks this release, is not warranted.

Aminophylline↗

PubMed1975

The action of aminophylline on the acutely transplanted dog heart: effect of alpha- and beta-adrenoceptor blockade.

1 Aminophylline inhibits the coronary vasodilator actions of adenosine. Our previous studies suggested that low dose infusions of aminophylline reduce coronary blood flow in the isolated heart. In the present study we investigated the actions of aminophylline on coronary blood flow and myocardial contractility in a transplanted heart model. Drugs were given by close coronary arterial infusion. 2 Aminophylline in low doses (200 mug/min) reduced coronary blood flow by 21 plus or minus 2% (mean plus or minus s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 mug/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 Alpha-adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 mug/min). 4 Propranolol in doses of 10 and 30mug/min blocked beta-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5 The effects of a high dose of aminophylline (1000 mug/min) on coronary blood flow were not changed by either alpha- or beta-adrenoceptor blockade, although propranolol (30 mug/min) reduced the augmentation in myocardial contractility. 6 The results show that when given in doses which do not alter myocardial contractility, aminophylline reduces coronary blood flow in the isolated heart and that this is not mediated through an alpha-adrenoceptor mechanism. They also show that the increases in coronary blood flow and positive inotropic effects obtained with higher doses of aminophylline are not mediated through catecholamines and suggest that higher doses of aminophylline have a small direct coronary vasodilator action. The low dose vasoconstrictor response may be produced by inhibition of the coronary vasodilator action of locally produced adenosine.

Adrenergic alpha-Antagonists↗

PubMed2005

Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.

BACKGROUND: Intravenous aminophylline is commonly used in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD), despite limited evidence for its efficacy and known risks of toxicity. We hypothesised that adding intravenous aminophylline to conventional treatment would not produce clinically important changes in the speed of spirometric or symptomatic recovery or shorten hospital stay in patients with exacerbations of COPD. METHODS: Eighty patients admitted to hospital with non-acidotic exacerbations of COPD were recruited at admission to a randomised, double blind, placebo controlled study comparing intravenous aminophylline 0.5 mg/kg/hour after an appropriate loading dose with an equivalent volume of 0.9% saline. The primary outcome was the change in post-bronchodilator forced expiratory volume in 1 second (FEV(1)) over the first 5 days of the admission. Secondary end points were changes in self-reported breathlessness, arterial blood gas tensions, forced vital capacity (FVC), and length of hospital stay. RESULTS: There was no difference in the post-bronchodilator FEV(1) over the first 5 days between the aminophylline and placebo groups. In the aminophylline group, 2 hours of treatment produced a small but significant rise in arterial pH (p = 0.001) and a fall in arterial carbon dioxide tension (p = 0.01) compared with placebo treatment. There were no differences in the severity of breathlessness, post-bronchodilator FVC, or length of hospital stay between the groups. Nausea was a more frequent side effect in the aminophylline group (46% v 22%; p<0.05), but palpitations and headache were noted equally in both groups. CONCLUSIONS: Although intravenous aminophylline produced small improvements in acid-base balance, these did not influence the subsequent clinical course. No evidence was found for any clinically important additional effect of aminophylline treatment when used with high dose nebulised bronchodilators and oral corticosteroids. Given its known toxicity, we cannot therefore recommend the use of intravenous aminophylline in the treatment of non-acidotic COPD exacerbations.

Aged↗

PubMed1989

Aminophylline enhances contractility of frog skeletal muscle: an effect dependent on extracellular calcium.

The effects of aminophylline (10-500 microM) on isometric twitch and tetanic forces were studied in vitro on frog semitendinosus muscle. Two hypotheses were tested: 1) that micromolar concentrations of aminophylline enhanced contractility of isolated skeletal muscle and 2) that the potentiating effect of aminophylline was dependent on the presence of extracellular calcium ions. Muscles were removed, placed in aerated Ringer solution at 20 degrees C, attached to a force transducer, and stimulated directly. Muscles in normal Ringer and aminophylline Ringer were compared throughout the frequency-force relationship from twitches to maximum tetanic force. Aminophylline increased twitch force significantly at concentrations as low as 25 microM. Over a range of stimulation frequencies, but especially at 10 and 20 Hz, aminophylline increased tetanic force. The potentiating effect of aminophylline (100 microM) was reduced or eliminated in calcium-free Ringer containing 10 mM magnesium. We conclude that aminophylline, at therapeutic concentrations, enhances muscle contractility, and the enhancement is dependent on the presence of extracellular calcium. These findings support the concept that aminophylline is effective in improving respiration in humans with airway obstruction by enhancing diaphragmatic contractility.

Aminophylline↗

PubMed1985

Comparative effects of aminophylline on diaphragm and cardiac contractility.

The mechanisms by which aminophylline increases inspiratory muscle contractility are unclear. The present study compared the effects of aminophylline on cardiac as well as on diaphragm contractility and examined the interaction of aminophylline with verapamil, a calcium channel-blocking agent, on both types of muscle. Experiments were performed in mongrel dogs anesthetized with pentobarbitone. Diaphragm contractility was assessed from transdiaphragmatic pressure (Pdi) developed during supramaximal electrical stimulation of the cervical phrenic rootlets, and cardiac contractility was assessed from peak left ventricular (LV) pressure and its rate of rise (dPv/dt). Measurements were made before and after each of 3 sequential IV infusions of aminophylline (6 mg/kg) and subsequent IV infusions of verapamil (0.1 mg/kg bolus and 0.02 mg/kg/min for 5 to 7 min.). Transient decreases in Pdi were frequently observed immediately after aminophylline infusion in association with decreases in mean arterial blood pressure. With recovery of mean blood pressure, Pdi increased above baseline values. Aminophylline increased Pdi in a dose-dependent fashion over the entire frequency range studied (1 to 40 Hz). Aminophylline increased the rate of rise of Pdi (dPd/dt) without affecting the period over which pressure was developed or dissipated during single twitches. Aminophylline increased both peak LV pressure and dPv/dt. The magnitude of the cardiac response was greater than the diaphragmatic response. Subsequent verapamil infusion completely reversed the effects of aminophylline on LV contractility but had only a small effect on diaphragm contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗

PubMed1992

Compatibility of ceftazidime and aminophylline admixtures for different methods of intravenous infusion.

OBJECTIVE: Aminophylline and ceftazidime are sometimes used concurrently in patients with respiratory disorders. Parenteral aminophylline usually is administered as a constant infusion, and ceftazidime is given intermittently or less commonly as a constant infusion. We evaluated the stability and compatibility of the two drugs when aminophylline is given as a constant intravenous infusion and ceftazidime is administered simultaneously either through a y-site (piggyback method) or as a continuous infusion (constant infusion method). DESIGN: The chemical stability of intravenous aminophylline and ceftazidime in dextrose 5% and NaCl 0.9% for both methods was studied. Three different formulations of ceftazidime from the same manufacturer were studied (minibag using reconstituted ceftazidime, premixed minibag, and ceftazidime arginine). For the piggyback and constant infusion methods, samples were collected at 0, 1, and 2 hours; and 0, 6, and 24 hours, respectively. All experiments were conducted in triplicate. Samples were analyzed in duplicate by a stability-indicating HPLC assay method. OUTCOME MEASURE: Ceftazidime and aminophylline were considered stable if concentrations remained above 90 percent of the original concentrations over the time periods studied. RESULTS: Ceftazidime was determined to be compatible with aminophylline in the piggyback method. In contrast, when aminophylline and ceftazidime were admixed in the same intravenous container (constant infusion method), the two drugs were not stable. CONCLUSIONS: These data indicate that aminophylline and ceftazidime admixtures are incompatible when prepared in the same intravenous container, which may occur if both are given as a constant infusion. The two drugs are compatible when the ceftazidime is piggybacked into a primary intravenous set in which aminophylline is administered as a constant infusion.

Aminophylline↗

PubMed2006

Effects of dexamethasone and aminophylline on survival of Jurkat and HL-60 cells.

The effects of dexamethasone and aminophylline on survival of Jurkat T-lymphocytic leukemia cells and HL-60 promyelocytic leukemia cells were investigated. Dexamethasone (10, 1000 nM) and aminophylline (1, 100 microM) induced apoptosis in Jurkat and HL-60 cells in a concentration-dependent manner. Treatment with a combination of dexamethasone (10 nM) and aminophylline (1 microM) significantly increased the number of apoptotic HL-60 cells, but not that of Jurkat cells, compared with dexamethasone (10 nM) or aminophylline (1 microM) treatment alone. Dexamethasone and aminophylline also increased the number of phospho-histone H2B (Ser(14))-positive Jurkat and HL-60 cells. Phospho-histone H2B (pH2B)-positive HL-60 cells were significantly increased by treatment with a combination of dexamethasone (10 nM) and aminophylline (1 microM), although no such effect was observed in Jurkat cells. On the other hand, simultaneous treatment with 10 nM dexamethasone and 1 muM aminophylline activated the 36-kDa MBP kinase, pro-apoptotic protein kinase in HL-60 cells. The activation of 36-kDa MBP kinase by dexamethasone and aminophylline was supported by studies showing an increase in the number of pH2B-positive and apoptotic Jurkat and HL-60 cells upon exposure to these drugs. Thus treatment with a combination of dexamethasone and aminophylline accelerates apoptosis of HL-60 cells via activation of 36-kDa MBP kinase and H2B phosphorylation.

Aminophylline↗

PubMed1980

Increased hypoxic ventilatory drive due to administration of aminophylline in normal men.

We evaluated the effects of intravenous administration and five days of oral administration of aminophylline on hypoxic and hypercapnic ventilatory drives in seven normal men. Serum levels of theophylline were 13.2 micrograms/ml +/- 1.0 micrograms/ml (mean +/- SD) after intravenous administration of aminophylline and 8.8 micrograms/ml +/- 1.7 micrograms/ml after oral administration of aminophylline. Aminophylline had no effect on the slope of the line for carbon dioxide response or on hypoxic ventilatory drive, measured at resting alveolar carbon dioxide tension (PACO2). Hypoxic ventilatory drive was significantly increased (P < 0.025) after intravenous administration of aminophylline when the PACO2 was raised to the control level before aminophylline. Intravenously administered aminophylline shifted the intercept of the line for carbon dioxide response from 40.7 +/- 2.3 to 32.9 +/- 4.6 mm Hg (P < 0.005) and lowered the resting PACO2 from 38.3 +/- 1.8 to 33.7 +/- 2.1 mm Hg (P < 0.005). Similar but smaller changes were seen after oral administration of aminophylline. There was a significant correlation between end-tidal carbon dioxide tension and the serum level of theophylline (P < 0.001), indicating that aminophylline stimulates ventilation in a dose-dependent fashion. This increase in ventilation is due in part to an increase in hypoxic ventilatory drive.

Administration, Oral↗

PubMed2005

Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators.

BACKGROUND: Since the advent of inhaled beta2-agonists, anticholinergic agents and glucocorticoids, the role of aminophylline in paediatric acute asthma has become less clear. There remains some consensus that it is beneficial in children with acute severe asthma, receiving maximised therapy (oxygen, inhaled bronchodilators, and glucocorticoids). OBJECTIVES: To determine if the addition of intravenous aminophylline produces a beneficial effect in children with acute severe asthma receiving conventional therapy. SEARCH STRATEGY: The Cochrane Airways Group register of trials was used to identify relevant studies. The latest search was carried out in December 2004 SELECTION CRITERIA: Randomised-controlled trials comparing intravenous aminophylline with placebo in addition to usual care in children met the inclusion criteria. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies and extracted data. Disagreement in the selection of trials was resolved by consensus. Attempts were made to contact authors to verify accuracy of data. MAIN RESULTS: Seven trials met the inclusion criteria (380 participants). Methodological quality was high. All studies recruited children with acute severe asthma and requiring hospital admission. Six studies sought participants who were unresponsive to nebulised short-acting beta-agonist and administered systemic steroids to study participants. In two studies where some children were able to perform spirometry, baseline FEV1 was between 35 and 45% predicted. The addition of aminophylline to steroids and beta2-agonist significantly improved FEV1% predicted over placebo at 6-8 hours, 12-18 hours and 24 hours. Aminophylline led to a greater improvement in PEF% predicted over placebo at 12-18 hours. There was no significant difference in length of hospital stay, symptoms, frequency of nebulsations and mechanical ventilation rates. There were insufficient data to permit aggregation for oxygenation and duration of supplemental oxygen therapy. Aminophylline led to a three-fold increase in the risk of vomiting. There was no significant difference between treatment groups with regard to hypokalaemia, headaches, tremour, seizures, arrhythmias and deaths. AUTHORS' CONCLUSIONS: In children with a severe asthma exacerbation, the addition of intravenous aminophylline to beta2-agonists and glucocorticoids (with or without anticholinergics) improves lung function within 6 hours of treatment. However there is no apparent reduction in symptoms, number of nebulised treatment and length of hospital stay. There is insufficient evidence to assess the impact on oxygenation, PICU admission and mechanical ventilation. Aminophylline is associated with a significant increased risk of vomiting.

Acute Disease↗

PubMedDate not supplied

Aminophylline reduces hypoxic ventilatory depression without increasing catecholamines.

Aminophylline reduces hypoxic ventilatory depression in newborn piglets and can enhance the release of catecholamines (CATs), which in turn may stimulate ventilation. To determine if the effect of aminophylline on ventilation was due to the release of CATs, we measured plasma CATs and ventilation in two groups of spontaneously breathing newborn piglets less than 4 days old, treated with either aminophylline (n = 7) or normal saline solution (n = 6) during both normoxia and hypoxia. The piglets were anesthetized with ketamine and xylazine and intubated, and the femoral artery was catheterized. Epinephrine and norepinephrine were measured before and 30 minutes after treatment with aminophylline (15 mg/kg) or normal saline. The animals were exposed to 10% oxygen and the CATs again measured after 5 minutes of hypoxia. Respiratory rate, expiratory flow integrated to minute ventilation (VE), heart rate, and blood pressure were continuously recorded. CATs were assayed by high-pressure liquid chromatography with electrochemical detection. Treatment with aminophylline during normoxia was associated with an increase in tidal volume. During hypoxia, treatment with aminophylline prevented a fall in VE and respiratory rate seen in the normal saline group. Epinephrine and norepinephrine increased during hypoxia, but there was no difference between the groups at 5 minutes. In our model the increase in CATs observed during hypoxia was not enhanced by aminophylline. This is consistent with the hypothesis that some mechanism other than catecholamine release is responsible for the effect of aminophylline in reducing neonatal hypoxic respiratory depression.

Aminophylline↗

PubMed1989

Improved exercise capacity with acute aminophylline administration in patients with syndrome X.

The efficacy of the adenosine receptor blocker aminophylline on exercise capacity in patients with effort ischemia and documented coronary artery disease has been previously documented. In this study the effect of aminophylline on effort electrocardiographic (ECG) alterations and chest pain was tested in eight patients with syndrome X (anginal chest pain on effort, ischemic ECG changes during exercise, positive dipyridamole test, normal epicardial coronary arteries on angiography and absence of coronary spasm after ergonovine). After double-blind, randomized intravenous infusion of aminophylline (6 mg/kg body weight over 15 min) or placebo (20 ml of saline solution over 15 min), the eight patients with syndrome X underwent an upright bicycle exercise stress test on 2 consecutive days. After aminophylline, there was an increase in effort tolerance (aminophylline 7.7 +/- 1.2 min of exercise versus placebo 5.6 +/- 0.9, p less than 0.01) paralleled by an increase of the rate-pressure product (mm Hg x beats/min x 1/100) at 0.1 mV of ST segment depression or at peak exercise (aminophylline 278 +/- 55 versus placebo 230 +/- 24, p less than 0.05). Aminophylline provoked the abolition of ECG signs of ischemia in all eight patients. Thus, at a dosage that should effectively inhibit adenosine receptors, aminophylline infusion exerts a beneficial effect on exercise-induced chest pain and ischemia-like ECG changes in syndrome X. This effect occurs possibly through the prevention of myocardial flow maldistribution elicited by inappropriate adenosine release during effort in the presence of increased coronary resistance at the level of small intramural coronary arteries. This study, however, does not document the ischemic nature of effort-induced pain and ECG alterations in syndrome X.

Adult↗

PubMed2006

Pretreatment with aminophylline reduces release of Troponin I and neutrophil activation in the myocardium of patients undergoing cardioplegic arrest.

OBJECTIVE: Cardioplegic arrest and subsequent reperfusion results in myocardial injury partly related to local inflammation in the heart. It has been proven that aminophylline has numerous anti-inflammatory effects. This study has been designed to evaluate the effects of aminophylline used as a cardioprotective agent for patients undergoing cardiopulmonary bypass (CPB) for valve replacement. METHODS: Thirty patients undergoing elective valve replacement were randomized to receive either aminophylline (n=15), or normal saline (control n=15). Administration of aminophylline (5mg/kg) was injected intravenously after induction of anesthesia. The cardiac Troponin I (cTnI), myocardial myeloperoxidase (MPO) activity, atrial cyclic AMP, and a coronary sinus neutrophil count were measured before and after cardioplegic arrest. RESULTS: There were no differences between the two groups with regard to clinical variables. The cTnI concentration increased significantly after aortic declamping in both groups. However, it was significantly lower, 8h after aortic declamping, in aminophylline group (1.00+/-0.41 vs 2.37+/-1.35 ng/ml p=0.038). The atrial cAMP was significantly higher before aortic cross-clamping in aminophylline group (42.5+/-6.7 pmol/g tissue vs 30.6+/-12.4 pmol/g tissue p=0.04). In addition, we found that the aminophylline group had a significantly lower MPO after reperfusion (1.50+/-0.58 U/g tissue vs 0.86+/-0.24 U/g tissue p=0.003), and a significantly lower neutrophil count 30 min after aortic declamping (0.68+/-0.11x10(3) cell/ml vs 0.32+/-0.16x10(3) cell/ml, p=0.023). CONCLUSIONS: Pretreatment with intravenous aminophylline reduces the subclinical myocardial injury and neutrophil activation in patients undergoing CPB for valve replacement.

Adult↗

PubMed2002

Aminophylline exacerbates status epilepticus-induced neuronal damages in immature rats: a morphological, motor and behavioral study.

Adenosine is an endogenous modulator that has an inhibitory effect on neuronal activity. The aim of this work was to investigate the role of aminophylline, an adenosine receptor antagonist, on the long-term effects of status epilepticus (SE) in the developing brain. Four groups of rats at the postnatal age of 12 days were intraperitoneally administered with saline, aminophylline (50 mg/kg), lithium-pilocarpine (Li-PC) (3 mEq/kg-60 mg/kg), and Li-PC plus aminophylline, respectively. The four groups were tested for spatial memory using the Morris water maze task at P80 and motor performance by the Rotarod test at P100. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. At the acute stage, all rats subjected to Li-PC developed SE and no seizures were elicited in the saline-treated or aminophylline-treated rats. The seizure duration was longer in the Li-PC plus aminophylline group (346.9+/-32.7 min) as compared with that in the Li-PC group (265.2+/-9.8 min). The difference of mortality was not significant. Rats without seizures exhibited no motor imbalance, spatial deficits, or morphological changes. The rats with Li-PC-induced SE demonstrated spatial memory deficits without motor incoordination or morphological changes. However, the rats subjected to Li-PC plus aminophylline exhibited motor impairment and morphological changes, including neuronal cell loss in CA1 area and increased mossy fiber sprouting in CA3 area. In addition, the rats of Li-PC plus aminophylline had greater spatial memory deficits than that seen in rats with Li-PC. We concluded that an adenosine receptor antagonist, such as aminophylline, had synergistic effects on the SE-induced long-term deficit of cognition and motor performance in the developing brain. The present study may provide experimental evidence and lead to novel therapeutic interventions.

Aging↗

PubMed1981

Aminophylline improves diaphragmatic contractility.

In an attempt to explain the clinical efficacy of aminophylline, we studied its effect on diaphragmatic function in eight normal subjects. The relation between the electrical activity of the diaphragm and the pressure generated by the diaphragm was assessed during voluntary contractions before and after aminophylline infusion. Aminophylline shifted the electrical activity/pressure curve to the left; the pressure at a given electrical activity increased an average of 15 per cent (P less than 0.001). In four subjects, pressure was also measured during stimulation of the phrenic nerve at various frequencies before and after diaphragmatic fatigue was produced by resistive breathing, with and without aminophylline infusion. Pressure increased after fatigue at all stimulation frequencies with aminophylline, as compared with the pressure after identical fatigue runs at the same stimulation frequencies without aminophylline. The mean plasma aminophylline concentration associated with these responses was 13 +/- 0.9 mg per liter. We conclude that aminophylline improves the diaphragm's contractility and renders it less susceptible to fatigue.

Adult↗

PubMed1987

Autonomic modulation of aminophylline influence on the electrophysiological effects of adenosine and adenosine triphosphate in the canine heart.

The influence of aminophylline, a competitive antagonist of adenosine, on the chronotropic and dromotropic effects of adenosine and adenosine triphosphate was studied in pentobarbital anaesthetised dogs under various modifications of the autonomic nervous tone. Adenosine and adenosine triphosphate (3 mumol.kg-1 each) were rapidly (greater than or equal to 1 s) injected into the right atrium during both sinus rhythm and right atrial pacing (cycle length 300 ms) before and after infusion of aminophylline (5 mg.kg-1) (n = 21) as well as after increasing doses of aminophylline (n = 10). Some dogs underwent either muscarinic blockade with atropine (0.2 mg.kg-1) (n = 10), or beta adrenergic blockade with propranolol (1 mg.kg-1) (n = 10), or complete autonomic blockade with atropine and propranolol (n = 10). Aminophylline (5 mg.kg-1) antagonised the negative chronotropic and dromotropic effects of adenosine triphosphate and adenosine in dogs pretreated with atropine or atropine plus propranolol but did not affect them in autonomically intact dogs. In addition, the electrophysiological effects of adenosine were antagonised by only the highest doses of aminophylline in autonomically intact dogs and by aminophylline (5 mg X kg-1) in dogs pretreated with propranolol. It was concluded that (a) alteration of the electrophysiological effects of adenosine triphosphate and adenosine by aminophylline is appreciably influenced by the autonomic nervous tone and (b) autonomic blockade is required for the manifestation of the antagonism by aminophylline of the electrophysiological action of adenosine and adenosine triphosphate.

Adenosine↗

PubMed1993

A randomized, controlled trial of aminophylline in ventilatory weaning of premature infants.

OBJECTIVES: To determine whether maximal inspiratory force predicts successful neonatal extubation, and whether aminophylline affects maximal inspiratory force or the success rate of extubation. DESIGN: Double-blind, prospective, randomized, placebo-controlled trial. SETTING: Tertiary level neonatal intensive care unit. PATIENTS: A total of 20 ventilated, preterm, newborn infants: birth weight < 2.5 kg; gestation < 35 wks. INTERVENTIONS: Intravenous aminophylline 4 mg/kg bolus followed by 2.5 mg/kg every 6 hrs x three doses, then 1.5 mg/kg every 6 hrs; or placebo. Drug administration began when infants were receiving an FIO2 of < 0.4 and were progressively weaning from assisted mechanical ventilation. A standardized weaning protocol was instituted, and patients were extubated when they were able to tolerate a mechanical ventilatory rate of < 5 cycles/min. MEASUREMENTS AND MAIN RESULTS: Occlusion pressures, including maximal inspiratory force, were measured before aminophylline and daily until endotracheal extubation. Arterial blood gases were measured every 3 hrs, and 24-hr cardiac and respiratory recordings were performed postextubation. Three of ten aminophylline-treated patients failed extubation compared with two of ten placebo infants (p = nonsignificant). Mean apnea frequency postextubation was 0.02/hr in the aminophylline group compared with 0.3/hr in the placebo group (p < .05). Aminophylline had no effect on successful extubation or on maximal inspiratory force. Maximal inspiratory force was not correlated with the success of extubation. Apnea frequency postextubation was significantly reduced by aminophylline. CONCLUSIONS: Aminophylline is an effective prophylaxis for postextubation apnea in the preterm infant but does not affect maximal inspiratory force or increase the success rate of extubation in this patient population.

Airway Resistance↗

PubMed1995

Aminophylline: could it act as an antioxidant in vivo?

Potential antioxidant properties of aminophylline and theophylline were investigated. We have found that these drugs, though ineffective against superoxide anion and hydrogen peroxide, are scavengers of hydroxyl radical (OH.). Indeed, second-order rate constants (k) of aminophylline and theophylline with OH. are about 1.9 x 10(10) mol-1 s-1 and 4.5 x 10(9) mol-1 s-1, respectively. Ethylenediamine, which is present in the aminophylline molecule, significantly contributes to this marked OH. scavenging activity, since it is characterized by a high k value, i.e. about 8 x 10(9) mol-1 s-1. However, when using therapeutically relevant concentrations of the methylxanthines (9 and 13 micrograms mL-1), significant antioxidant effects against OH.-induced oxidant injury are evident only with aminophylline. Although all three substances can apparently bind and inactivate iron, only aminophylline is effective at 9 and 13 micrograms mL-1; also this action is favoured by ethylenediamine. Moreover, therapeutic concentrations of aminophylline, but not of theophylline, are capable of antagonizing hypochlorous acid (HOCl); this effect is entirely due to the presence of ethylenediamine. Oxidant species, such as OH. and HOCl, have been implicated in the pathophysiology of asthma; it could be hypothesized, therefore, that some therapeutic effects of aminophylline may be related to its antioxidant properties, which are partly or totally attributable to ethylenediamine, depending on the chemical identity of the prooxidant antagonized (e.g. iron/OH. or HOCl). Aminophylline antioxidant capacity should be taken into account when investigating the lung epithelial lining fluid antioxidant capacity and oxidative stress indices in humans.

Aminophylline↗

PubMed1993

Effect of aminophylline on respiratory muscle strength after upper abdominal surgery: a double blind study.

BACKGROUND: The effect of aminophylline on maximum respiratory muscle strength in patients undergoing upper abdominal surgery was investigated. METHODS: An open pilot study was performed in which aminophylline was administered continuously for 48 hours after surgery (protocol I). In a second group of subjects aminophylline was given for 24 hours after cholecystectomy in a double blind placebo controlled trial (protocol II). Twelve patients participated in the pilot study (group A) and 25 in protocol II of which 14 received aminophylline (group B) and 11 placebo (control, group C). Respiratory muscle strength was assessed by measuring mouth pressures during maximum static inspiratory and expiratory efforts. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), vital capacity (VC), inspiratory maximum pressures (PImax), expiratory maximum pressures (PEmax) were measured 24 hours preoperatively, PImax and serum theophylline 24 hours postoperatively, and FEV1, FVC, VC, PImax, PEmax, and serum theophylline 48 hours after surgery. RESULTS: FEV1, FVC, and VC decreased in all groups of patients at +48 hours. PImax fell at +24 hours and +48 hours but this decrease was significantly smaller in the two groups who received aminophylline than in the control group. PEmax showed a decrease at +48 hours but this reduction was similar in all three groups studied, independent of the treatment given. These data suggest that either aminophylline had a protective effect only on the inspiratory muscles or, most probably, that the effect of aminophylline was central, reducing the phrenic nerve inhibition induced by cholecystectomy and thus improving diaphragmatic function. CONCLUSIONS: Upper abdominal surgery decreases inspiratory and expiratory muscle strength and aminophylline has a protective effect only on inspiratory muscle function. This may have important clinical applications in minimising pulmonary complications after cholecystectomy.

Abdomen↗