Ml Van de Weerdt

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.

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 (ΔPtp) 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 ΔPtp 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.