Role of the cholinergic pathway in mediating platelet-activating factor-induced pulmonary dysfunctions in unsedated calves.

The purpose of this study was to investigate the possible role of the cholinergic pathway in mediating platelet-activating factor (PAF)-induced pulmonary dysfunctions in unsedated calves. In a placebo group, PAF infusion challenge induced significant dysfunctions in the pattern of breathing [a significant increase in respiratory rate (RR) and a significant decrease in tidal volume (VT)], the mechanics of breathing [a significant increase in total lung resistance (RL) and a significant decrease in dynamic lung compliance (CLdyn)] and gas exchange, whereas in atropine pre-treated calves, PAF infusion challenge induced a significant increase in RR, VT and HR and a significant decrease in CLdyn. The RL increase was prevented by atropine pre-treatment. On the basis of our findings, we suggest that, in cattle, the PAF-induced pattern of breathing dysfunctions and the diffuse bronchoconstriction and microvascular leakage of small airways are not mediated through the cholinergic pathway. By contrast, our data suggest that PAF-induced bronchoconstriction of upper airways is at least partly mediated through muscarinic receptors.

Ketoprofen and phenylbutazone attenuation of PAF-induced lung inflammation in calves.

The purposes of this study were: (1) to investigate which arachidonic acid metabolites contributed to platelet-activating factor (PAF) induced pulmonary dysfunction; and (2) to compare the effect of two non-steroidal anti-inflammatory drugs, phenylbutazone and ketoprofen in a model of PAF-induced reversible lung inflammation in six calves. In placebo and phenylbutazone groups, PAF infusion induced significant dysfunctions in the pattern of breathing, mechanics of breathing and gas exchange. These dysfunctions were prevented by ketoprofen pretreatment, except for the mechanics of breathing which was moderately but significantly altered by the PAF challenge. In all calves, leukotriene (LT) B4 plasma concentrations did not significantly increase above baseline values at any time. Prostaglandin (PG) E2 plasma concentrations showed a minor significant increase in phenylbutazone pretreated calves (55.8 +/- 25.8 pg/mL from 36.7 +/- 16.13 pg/mL). Thromboxane (TX) B2 plasma concentration was significantly increased during PAF challenge in placebo- and phenylbutazone-pretreated groups, but not in ketoprofen-pretreated calves (1580.0 +/- 1370 from 42.7 +/- 10.7 pg/mL; 2340 +/- 477 from 63 +/- 32 pg/mL; and 36.5 +/- 4.12 from 39.3 +/- 12.0 pg/mL, respectively). These data suggest that TXA2 is an important cyclooxygenase metabolite of arachidonic acid produced in response to PAF and that ketoprofen (intramuscular injection, 3 mg/kg) is more effective than phenylbutazone (intramuscular injection, 10 mg/kg) in preventing respiratory dysfunctions induced by the PAF challenge 30 min after drug administration. Ketoprofen did not suppress totally the PAF-induced changes in mechanics of breathing, which suggests that PAF or a secondary release of mediators could have a direct action on airway smooth muscle.

Effect of platelet-activating factor on bovine pulmonary function.

The objectives of this study were to determine whether the infusion of platelet-activating factor would modify bovine pulmonary function, heart rate and platelet count and whether any such modifications could be antagonised by the prior intravenous injection of a specific antagonist (WEB 2086). In saline-pretreated calves, the respiratory rate, total lung resistance (RL) and maximal changes in transpulmonary pressure (delta Ptp) were significantly increased whereas lung dynamic compliance (CLdyn), tidal volume (VT), platelet count and heart rate were significantly decreased. The changes in RL, CLdyn, VT and delta Ptp were abolished by pretreatment with WEB 2086, whereas respiratory rate remained significantly increased to 125 per cent of the baseline value, but less than in the saline-pretreated calves in which it was 250 per cent of the baseline value.

Effect of serotonergic blockade on calf pulmonary function after the intravenous administration of 3-methylindole.

This study was designed to investigate whether 3-methylindole (3-Mi), a tryptamine analogue, could cause pulmonary injury in calves other than by cytotoxicity. Injection of 3-Mi resulted in a marked increase of respiratory rate, decrease of tidal volume and increase in minute ventilation. Pulmonary mechanics values were also profoundly affected, lung dynamic compliance being reduced to approximately one-third of its baseline value and total pulmonary resistance being increased two-fold. Arterial oxygen partial pressure was dramatically reduced. Successive challenges with 3-Mi after physiological saline pretreatment resulted in quantitatively identical alterations of pulmonary function values. Conversely, all these ventilatory, mechanical and gas exchange changes were abolished by pretreatment with serotonergic antagonists. It was concluded that intravenous administration of 3-Mi to healthy calves induced immediate and reversible bronchoconstriction which affected both central and peripheral airways. Because the effect was abolished by pretreatment with antiserotonin drugs, it is suggested that 3-Mi acts either directly by stimulating serotonergic receptors or indirectly through the release of serotonin from platelets. Current concepts of the physiopathological cascade underlying the toxicity of 3-Mi should, therefore, be re-evaluated in the light of this pharmacological mechanism.