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I Erjefält

Publications and source records attributed to I Erjefält.

49 records · Page 3Linked to original sources
PubMed1986

Leakage of macromolecules from guinea-pig tracheobronchial microcirculation. Effects of allergen, leukotrienes, tachykinins, and anti-asthma drugs.

The tracheobronchial mucosa of anaesthetized guinea-pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min-1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelled in vivo with 99Tcm, and analysing for FITC-dextran, MW = 70,000, that had been given i.v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC-dextran. Capsaicin 0.1 nmol extravasated 223 micrograms of FITC-dextran per g wet weight of airway tissue (P less than 0.001). Substance P 0.1 nmol, 41 micrograms g-1 (P greater than 0.05); substance P 0.3 nmol, 142 micrograms g-1 (P less than 0.001); eledoisine 0.1 nmol, 101 micrograms g-1 (P less than 0.01); ovalbumin 0.1 microgram, 179 micrograms g-1 (P less than 0.001); LTC4 0.2 pmol, 180 micrograms g-1 (P less than 0.001); LTD4 0.2 pmol 223 micrograms ml-1 (P less than 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion (0.02 ml min-1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extravasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vascular permeability to macromolecules is subject to physiological and pharmacological control.

Adrenergic beta-Agonists↗
PubMed1985

Anti-asthma drugs and capsaicine-induced microvascular effects in lower airways.

Substance P, capsaicine and bicervical vagal stimulation may increase microvascular permeability to macromolecules in lower airways. In previous studies techniques were employed that could have adversely affected the microvasculature. An atraumatic method of exposing the guinea-pig trachea to constant concentrations of drugs followed by quantitation of the blood-pool (in vivo 99Tcm-labelled erythrocytes) and extravasated macromolecules (Fitc.-dextran) has now been developed. Capsaicine produced marked extravasation of Fitc.-dextran while substance P in the concentration tested merely had vasodilator properties. Pretreatment with lidocaine, the beta-receptor agonist, terbutaline, or the adenosine non-blocking xanthine, enprofylline, inhibited the capsaicine induced inflammatory response.

Animals↗
PubMed1982

Tracheal relaxant and cardiostimulant actions of xanthines can be differentiated from diuretic and CNS-stimulant effects. Role of adenosine antagonism?

Theophylline (1, 3-dimethylxanthine) and enprofylline (3-propylxanthine) have been examined for effects in the rat. Enprofylline was 3.8 times as potent as theophylline as a tracheal relaxant in vitro, and 1.3 times as potent as theophylline to increase the rate of isolated perfused hearts. An oral dose (5 mg/kg) of enprofylline to rats was almost completely recovered in the urine as unchanged drug, showing that this xanthine is well absorbed and negligibly metabolised. Theophylline (10 and 30 mg/kg p.o.) significantly and dose-dependently increased locomotor activity in rats whereas the same doses of enprofylline were without effect on behaviour. Theophylline ( 5-20 mg/kg p.o.) produced significant and dose-dependent natriuretic and volume diuretic effect with little augmentation of potassium excretion. Enprofylline up to 10 mg/kg was without diuretic effects. At the large dose of 20 mg/kg enprofylline decreased sodium excretion and produced some volume diuresis. It is suggested that lack of diuretic and CNS-stimulant behavioural effects by enprofylline is due to its low ability to antagonise adenosine receptor stimulation. Pharmacodynamic differences between enprofylline and the potent adenosine antagonist theophylline may indicate a functional importance of endogenous adenosine.

Adenosine↗
PubMed1982

Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives.

Relaxant effects and adenosine-antagonism of 3-propyl-xanthine (enprofylline) and 10 different methyl-xanthines were examined in isolated guinea-pig tracheas. The chemical structural requirements for tracheal relaxation were found to be different from those for adenosine antagonism by the xanthine derivatives. All xanthines produced relaxation: Enprofylline was about 5 times more potent than theophylline. However, only xanthines with a methyl in the 1-position consistently antagonized the relaxant effect of adenosine. --Theophylline over a wide range of concentrations (30-900 microM) produced a concentration dependent and surmountable antagonism at nervous adenosine receptors (isolated guinea-pig myenteric-plexus preparations). The same concentrations of enprofylline were almost devoid of antagonism at these adenosine receptors. In mice theophylline (6-24 mg/kg given intraperitoneally) dose-dependently increased locomotor activity while enprofylline (2-48 mg/Kg) was without effect on behaviour. "Non-blocking" xanthines such as enprofylline may be potent bronchodilators but lack many theophylline-like actions. We, therefore, forward the hypothesis that universal adenosine antagonism is both unnecessary and undesirable with xanthine antiasthmatics.

Adenosine↗
PubMed1982

Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action.

Theophylline, that is a potent adenosine receptor antagonist, and enprofylline (3-propylxanthine), that seems to lack antagonism of neuronal depressant effects of adenosine, have been tested for convulsive activity in three animal species. In urethane-anaesthetized guinea-pigs theophylline produced massive generalized convulsions. Enprofylline was without any seizure activity but produced about the same changes as theophylline in heart rate, blood pressure, respiratory rate (less marked) and blood gas status. The lethal infused dose of enprofylline ws about twice as large as that of theophylline. This should be compared with the observation that enprofylline is about 5 times more potent than theophylline as a bronchodilator. Also in conscious guniea-pigs, mice and cats enprofylline was shown to be devoid of theophylline-like seizure activity. The CNS-stimulant effects of lethal doses of theophylline progressed until death occurred. The major behavioral effects of lethal doses of enprofylline in contrast were inhibition of activity and sedation. It is suggested that lack of seizure-activity reflects inability of enprofylline to antagonize neuronal depressant effects of endogenous adenosine.

Animals↗
PubMed1981

Convulsive effect of theophylline in conscious and anaesthetized guinea-pigs.

In urethane-anaesthetized guinea-pigs, the effect of theophylline (theo) on heart rate, arterial blood pressure, respiration rate and limb movements were recorded. Continuous intravenous infusion of theo initially increased the respiratory and heart rates and lowered the arterial blood pressure. After infusion of about 50 mg/kg of theo, the cardiovascular effects reached a maximum and were then only slightly changed until the terminal stage. A tonic stretching of the limbs (at 155 +/- 15 mg/kg) preceded generalized seizures of clonic tonic convulsions which were recorded after infusion of 367 +/- 25 mg/kg of theo. At this stage, respiration was highly irregular. PaO2 started to fall and PaCO2 to rise, while a plasma acidosis developed rapidly. The convulsions progressed in frequency and intensity and were terminally associated with respiratory and cardiovascular collapse. The convulsive effects of theophylline were similar to those observed in conscious guinea-pigs after 250 mg/kg of theo orally. The present findings agree with the view that the convulsive effect is a primary life-threatening action of theophylline. The method described may be of use in the search for new, less toxic xanthine drugs.

Administration, Oral↗
PubMed1979

Terbutaline and adrenaline inhibit leakage of fluid and protein in guinea-pig lung.

The effect of terbutaline (0.3 mg/kg s.c.) and adrenaline (0.1 and 0.3 mg/kg s.c.) on histamine--aerosol-induced increase in lung weight and dye content was studied in conscious guinea pigs, previously given Evans blue dye. Both drugs prevented the effects of histamine. It is concluded that terbutaline and adrenaline have a pronounced anti-permeability effect in guinea-pig lungs inhibiting the histamine-induced microvascular efflux of fluid and protein.

Aerosols↗
PubMed1979

Vascular anti-permeability effects of beta-receptor agonists and theophylline in the lung.

In conscious guinea-pigs the effect of theophylline, terbutaline and isoprenaline on histamine-induced increase in lung weight was examined. Animals exposed to a saline aerosol had a lung weight to body weight ratio of about 0.8%. Exposure to a histamine aerosol raised this value to about 1.1 (P less than 0.001). Theophylline 55 mg/kg and 110 mg/kg was given orally, terbutaline 0.1 mg/kg and isoprenaline 0.01 mg/kg and 0.03 mg/kg subcutaneously before exposure to histamine. The three drugs prevented the lung weight effect produced by histamine aerosol (P less than 0.01, P less than 0.001, P less than 0.001, P less than 0.1, P less than 0.001 respectively). Changes in lung blood content did not contribute to the weight-reducing effects. The potency ratio found between terbutaline and isoprenaline suggests that beta-2-receptors might be involved in the anti-permeability effect. Propranolol-treated animals did not survive in the histamine-aerosol unless they received theophylline; neither bronchodilator nor antipermeability effects of theophylline were antagonized by propranolol. It is concluded that in guinea-pigs theophylline and beta-agonists, in bronchodilating doses have the additional effect of preventing permeability oedema in the lung.

Administration, Oral↗
PubMed1978

Terbutaline preventing permeability effects of histamine in the lung.

In unanaesthetized guinea-pigs the effect of terbutaline on histamine-induced increase in lung weight was studied. Terbutaline 0.1 mg/kg and 0.3 mg/kg was given subcutaneously 5 min. before exposure during 60 min. to a histamine aerosol. Terbutaline markedly prevented the histamine-induced increase in lung weight. This effect is discussed in relation to the mechanism of action of mediator-induced increase in vascular permeability.

Animals↗
PubMedDate not supplied

Positive inotropic and chronotropic effects and coronary vasodilation in vitro by two antiasthmatic xanthines with different abilities to antagonize adenosine.

The direct actions and the ability to antagonize adenosine of theophylline (1,3-dimethylxanthine) and enprofylline (3-propylxanthine) were examined in isolated guinea pig heart preparations. Enprofylline was approximately six times as potent as theophylline in reducing coronary perfusion pressure, and between three and five times more potent in increasing rate and force of contraction in isolated perfused hearts, spontaneously beating right atrias, and electrically stimulated left atrias. Adenosine reduced the coronary perfusion pressure and had negative inotropic and chronotropic actions. Theophylline (5-75 microM) concentration-dependently antagonized the coronary vasodilation and the negative chronotropic and inotropic actions of adenosine, whereas enprofylline (2.5-75 microM) did not antagonize adenosine. Since adenosine may be a protective autacoid in the heart under select stress conditions, the possibility that adenosine nonblocking xanthines, like enprofylline, may offer therapeutic advantages over theophylline should be investigated.

Adenosine↗