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Biomedical subjects

I W Rodger

Publications and source records attributed to I W Rodger.

At least 91 records · Page 5Linked to original sources
PubMed1986

Effect of verapamil and sodium cromoglycate on leukotriene D4 induced bronchoconstriction in patients with asthma.

Leukotriene D4 (LTD4) may be an important mediator in asthma. The effect of verapamil and sodium cromoglycate on LTD4 induced bronchoconstriction has been examined in seven patients with asthma. The bronchoconstrictor response to increasing concentrations of inhaled LTD4 (0.0032-50 micrograms/ml) was assessed by measuring changes in FEV1, specific airways conductance, and flow rate at 30% of vital capacity (V30(p)). Results were expressed as the provocation concentration (PC) producing a 10% fall in FEV1 (PC10FEV1), a 35% fall in specific airways conductance (PC35SGaw), and a 30% fall in flow at 30% of vital capacity (PC30 V30(p)). Neither verapamil nor cromoglycate inhibited LTD4 induced bronchoconstriction in asthmatic subjects. These results suggest that in asthmatic patients LTD4 induced bronchoconstriction is not mediated via verapamil or cromoglycate sensitive mechanisms.

Adult↗
PubMed1985

Airway responsiveness to histamine in man: effect of atropine on in vivo and in vitro comparison.

Airway responsiveness to histamine in man may be determined by the smooth muscle sensitivity to histamine or to the interaction between vagal nerve input and smooth muscle sensitivity. We have compared in vivo responsiveness to histamine with in vitro smooth muscle sensitivity to histamine in 20 non-asthmatic patients and one asthmatic patient undergoing thoracic surgery. Histamine responsiveness was assessed in the first 10 non-asthmatics without atropine pretreatment, in the second 10 after atropine pretreatment, and in the asthmatic patient both with and without atropine. In vivo responsiveness was also measured in 10 normal subjects and 10 asthmatic patients not undergoing surgery. Results were expressed as the provocation concentration (PC) causing a decrease in FEV1 of 20% (PC20FEV1) and in specific airways conductance of 35% (PC35SGaw), and in terms of maximal expiratory flow at 35% vital capacity, measured from the partial (V35(P] and complete (V35(C] flow volume curves of 35% (PC35V35(P); PC35V35(C]. In vitro smooth muscle sensitivity to histamine of bronchial tissue obtained at thoracotomy was expressed as the concentration causing a 50% maximum contraction (EC50) and as the maximum tension generated. There was considerable variation between patients in the in vivo responsiveness but a relatively narrow range for in vitro responses. There was no significant correlation between in vivo responsiveness, either with or without atropine pretreatment, and in vitro results. The asthmatic patient showed hyperresponsiveness in vivo but but not in vitro. These results suggest that in vitro airway smooth muscle sensitivity to histamine is not the sole determinant of in vivo airway responsiveness and that this lack of relationship is not explained by the influence of vagal nerve input on in vivo measurements. The results in the asthmatic patient suggest that airway hyperresponsiveness may be an in vivo phenomenon which is not related to a primary abnormality of airway smooth muscle.

Adult↗
PubMed1985

The relationship between coronary artery occlusion-induced arrhythmias and myocardial cyclic nucleotide levels in the anaesthetized rat.

The aims of this study were to determine whether a relationship exists between the occurrence of coronary artery occlusion-induced arrhythmias in the anaesthetized rat and the levels of cyclic AMP and cyclic GMP in both normal and ischaemic myocardium, and to assess whether such arrhythmias were modified by pretreatment with the phosphodiesterase inhibitors, quazodine and isobutyl methylxanthine (IBMX), or with the butyryl derivatives of cyclic AMP and cyclic GMP. At 5 min after coronary artery ligation (when only a few arrhythmias had occurred) both cyclic AMP and cyclic GMP levels were elevated in normal myocardium whereas in ischaemic tissue only cyclic AMP was raised. As the peak of the arrhythmic activity and after cessation of the arrhythmias, i.e. at 10 and 30 min post-ligation respectively, levels of both nucleotides had fallen in ischaemic although not in normal tissue. The severity of these occlusion-induced arrhythmias was exacerbated by pretreatment intravenously with quazodine, IBMX, dibutyryl cyclic AMP and dibutyryl cyclic GMP. Pretreatment with IBMX was also shown to elevate significantly both cyclic AMP and cyclic GMP content of left ventricular tissue before occlusion. None of the drug pretreatments markedly affected mean arterial blood pressure but heart rate was significantly increased following quazodine and IBMX administration. We conclude that in the pentobarbitone-anaesthetized rat the occurrence of occlusion-induced arrhythmias was not accompanied by a rise in cyclic nucleotide content of the ischaemic myocardium but agents which may elevate either myocardial cyclic AMP or cyclic GMP levels exacerbate such arrhythmias.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Cyclic nucleotides and contractility of isolated soleus muscle.

The effects of isoprenaline, terbutaline and forskolin were examined on cyclic nucleotide concentrations and contractile responses in guinea-pig isolated soleus muscles. Isoprenaline and terbutaline induced rapid, concentration-related reductions in the tension and degree of fusion of subtetanic contractions of the soleus muscle. These changes were associated with increases (about 2 fold) in the levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the muscle cells. Propranolol competitively inhibited these responses. Forskolin failed to elicit a sympathomimetic response in the soleus muscles despite increasing (by about 20 fold) the intracellular concentration of cyclic AMP. Forskolin also failed to potentiate the effects induced by isoprenaline. The levels of cyclic GMP in the soleus were increased by isoprenaline (about 1.5 fold) and forskolin (about 2.5 fold). Terbutaline was without effect on cyclic GMP levels. These data suggest either that cyclic AMP is not involved as the mediator underlying beta-adrenoceptor-induced changes in contractility of slow contracting skeletal muscles or that forskolin does not stimulate the particular adenylate cyclase that leads to appropriate increases in cyclic AMP in those functional compartments associated with modulation of intracellular Ca2+ movements. Cyclic GMP is not involved in modifying changes in contractility of the soleus muscle.

Animals↗
PubMed1984

Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit.

The effects of forskolin, isoprenaline, sodium nitroprusside and the frequency of stimulation were examined on cyclic nucleotide levels and tension responses in rabbit isolated right ventricular papillary muscles. Increasing the frequency of stimulation from 0.01 Hz to 1.6 Hz induced positive inotropic responses that were not obviously related to alterations in the level of either cyclic AMP or cyclic GMP. Isoprenaline induced rapid, concentration-related positive inotropic responses that were associated with increases in the levels of both cyclic AMP and cyclic GMP. There existed good correlations between the increases in tension and the concentrations of both cyclic nucleotides measured in the tissues. Forskolin induced concentration-related positive inotropic responses that were slow to develop. These responses were accompanied by concentration-related increases in the levels of cyclic AMP but not cyclic GMP. The tension responses correlated well with the levels of cyclic AMP measured. The cyclic AMP levels produced by forskolin were some 8 fold higher than those induced by isoprenaline for similar increases in tension. Sodium nitroprusside was without inotropic effect either positive or negative; it nevertheless elevated cyclic GMP levels whilst slightly reducing cyclic AMP levels. These data show that the ratio of cyclic AMP to cyclic GMP does not correlate well with changes in mammalian cardiac contractility. The data further suggest that whilst the intracellular concentration of cyclic AMP in rabbit ventricular myocardium may be an important determinant of positive inotropism, the relationship between the two parameters is more complex than simple proportionality between the tension generated and the amount of cyclic AMP measured within the cells.

Animals↗
PubMed1984

Lack of effect of leukotriene D4 on Ca-uptake in airway smooth muscle.

The effects of verapamil on leukotriene D4 (LTD4)- and KCl-induced contractions and 45Ca-uptake were examined in guinea-pig isolated tracheal smooth muscle. Both LTD4 (0.1 to 200 nmol l-1) and KCl (8 to 125 mmol l-1) produced concentration-dependent increases in tension in the tracheal preparations. Verapamil (1 mumol l-1) inhibited the tension responses induced by both LTD4 and KCl. LTD4 failed to increase the lanthanum-resistant Ca content of tracheal smooth muscle at either low (EC25; 3 nmol l-1) or high (EC90; 50 nmol l-1) concentrations. Verapamil did not modify this result. KCl (90 mmol l-1) increased the lanthanum-resistant Ca content of the smooth muscle by approximately 60% over basal levels. This effect was completely inhibited by verapamil (1 mumol l-1). It is concluded that in this tissue, LTD4 utilizes principally an intracellular source of Ca2+ to initiate contraction whereas KCl is dependent upon the uptake of Ca2+ from the extracellular compartment. It is suggested that the inhibitory effects of verapamil may reflect an intracellular mechanism of action directed against Ca2+ release initiated by LTD4.

Animals↗
PubMed1984

Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man.

Airway responsiveness to methacholine varies between normal people and is increased in patients with asthma. The importance of airway smooth muscle sensitivity in determining in vivo responsiveness is unknown. We have examined this question by comparing in vivo airway responsiveness with in vitro airway smooth muscle sensitivity to methacholine in 10 patients undergoing thoracic surgery. In vivo responsiveness was determined by administration of inhalations of doubling concentrations of methacholine. Results were expressed as the provocation concentration (PC) causing a decrease in forced expiratory volume in one second of 20% (PC20FEV1), specific airway conductance of 35% (PC35SGaw), and maximal expiratory flow at 35% vital capacity, measured for the partial (V35(p)) and complete (V35(c)) flow volume curves, of 35% (PC35V35(p); PC35V35(c)). In vitro airway smooth muscle sensitivity was determined from specimens obtained at thoracotomy. Log dose-response curves to methacholine were constructed and the concentration causing a 50% maximum contraction (EC50) was derived. There were differences between patients for both in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine. There were no significant relationships between the in vivo and in vitro measurements. The results suggest that factors other than solely the sensitivity of smooth muscle must determine in vivo airway responsiveness to methacholine.

Adult↗
PubMed1983

The release of prostanoids during the acute pulmonary response to E. coli endotoxin in anaesthetized cats.

1 The administration of E. coli endotoxin (2 mg/kg i.v.) to anaesthetized cats results in a characteristic acute pulmonary response. This consists of increases in pulmonary artery pressure and airways resistance and a reduction in lung compliance. 2 Plasma concentrations of prostaglandin E2 (PGE2), PGF2 alpha, thromboxane B2 and 6-keto PGF1 alpha were measured by radioimmunoassay in aortic and pulmonary arterial blood samples before, during and after the acute pulmonary response to endotoxin. 3 Endotoxin administration resulted in the rapid release of PGF2 alpha and thromboxane B2 from the lungs. The time course of this release was parallel to that of the pulmonary hypertensive and airways responses to endotoxin. PGE2 and 6-keto PGF1 alpha were released more gradually and with greater variations between individual animals. 4 During the delayed shock phase (2 h after endotoxin) the concentrations of PGE2, PGF2 alpha and 6-keto PGF1 alpha were once again elevated in both the aorta and pulmonary artery. Thromboxane B2 concentrations were not increased at this time. 5 These results suggest that PGF2 alpha and thromboxane A2 may be mediators of the acute pulmonary responses to endotoxin.

Anesthesia↗
PubMed1983

The effect of a selective 5-HT2 antagonist, ketanserin, on the pulmonary responses to Escherichia coli endotoxin.

5-Hydroxytryptamine (5-HT, 5-160 microgram kg-1) injected intravenously in pentobarbitone-anaesthetized, open-chest cats caused dose-dependent increases in pulmonary arterial and intratracheal pressures. There was also a marked systemic hypotension and bradycardia. The pulmonary effects were completely prevented by ketanserin (0.2 mg kg-1), a selective 5-HT2 blocking drug. Ketanserin (0.2 mg kg-1) itself lowered arterial pressure (by 30-40 mmHg) but this systemic hypotension was relatively transient. Endotoxin (E. coli) administration resulted in pulmonary hypertension, increases in intratracheal pressure and airways resistance and reductions in lung compliance and in arterial PO2. Only the airways resistance response was modified by ketanserin (0.2 mg kg-1), suggesting a relatively unimportant role for 5-HT in mediating the acute, pulmonary effects of endotoxin in this species. The reductions in arterial (mixed venous) pH and in PO2 that resulted from endotoxin administration were not affected by pretreatment with ketanserin.

Animals↗
PubMed1981

Actions of 4-aminopyridine on the cardiovascular systems of anaesthetized cats and dogs.

The effects of the anti-curare agent 4-aminopyridine on the cardiovascular systems of cats and greyhounds under barbiturate-chloralose anaesthesia have been studied. In both species, 4-amino-pyridine produced a transient atropine-sensitive decrease in arterial pressure followed by a prolonged adrenergically-mediated increase. In the cat, the cardiac responses to vagal stimulation and nictitating membrane responses to sympathetic stimulation were augmented after injection of 4-aminopyridine, and the evidence indicated that these effects were the results of increased release of neurotransmitters. In the greyhound, 4-aminopyridine produced increases in the left ventricular systolic pressure and dP/dt max, right atrial pressure, stroke volume, myocardial blood flow, myocardial oxygen consumption, external cardiac work, arterial oxygen content and blood haemoglobin. These effects were attributable to facilitation of sympathetic transmission to the blood vessels, heart and spleen. Heart rate was not much affected because facilitation of vagal transmission to the S-A node counteracted the increased sympathetic effect. In the greyhound, 4-aminopyridine also produced temporary cardiac arrhythmia which was only partly attributable to facilitated sympathetic transmission. In addition there was evidence of a central stimulant action of 4-aminopyridine and of a stimulant action on visceral activity. It is concluded that, while 4-aminopyridine may be useful in certain relatively rare conditions of neuromuscular transmission failure, its actions are too widespread for routine use as an antagonist to non-depolarizing neuromuscular blocking drugs.

4-Aminopyridine↗
PubMed1979

Actions of two dopamine derivatives at adreno- and cholinoceptors.

Salsolinol (1)and 6,7-dihydroxy-1,1-dimethyl-1,2,3,4-tetrahydroisoquinoline hydrobromide (2) were synthesized and their effects at adreno- and cholinoceptors investigated both in vivo and in vitro. Both 1 and 2 produced agonist effects at cholinoceptors and alpha- and beta-adrenoceptors. Neuromuscular blocking actions were evident in vitro. Compound 2 exhibited anticholinesterase properties both in vivo and in vitro. These results indicate that dopamine derivatives of this type exhibit not only sympathomimetic activity but also complex actions at cholinoceptors.

Animals↗
PubMed1976

Actions of the muscle relaxant chandonium iodide on guinea-pig ileum and vas deferens preparations.

The effects of the newly synthesized neuromuscular blocking agent, chandonium iodide (17a-methyl-3beta-pyrrolidino-17a-aza-D-homo-5-androstene dimethiodide) have been investigated on guinea-pig isolated ileum and vas deferens preparations. On the ileum, chandonium (0-1-10-0 mug ml(-1); 1-6 X 10(-7) M-1-6 X 10(-5) M) had weak muscarinic receptor blocking action (pA2 is 5-7), but no antihistamine properties at the concentration tested. No evidence for anticholinesterase actions was found. On the vas deferens, chandonium (10-50 mug ml(-1); 1-6-8-1 X 10(-5) M) potentiated responses to exogenous noradrenaline; responses to electrical stimulation were potentiated only in the presence of 50 mug ml(-1) chandonium. No adrenoceptor or adrenergic neuron blockade was found. The results provide evidence that chandonium acts selectively at acetylcholine receptors and that it is more active as a nicotinic receptor antagonist than as a muscarinic receptor antagonist.

Acetylcholine↗