The role of platelets in the reflex tachypnoeic response to miliary pulmonary embolism in anaesthetized rabbits

Abstract

SUMMARYExperiments were performed upon twenty-eight male Californian rabbits anaesthetized with sodium pentobarbitone and breathing room air. Successive injections of glass bead emboli (diameter 125,am) caused an increase in respiratory rate, and decreases in tidal volume (tachypnoeic response) and platelet count. The tachypnoeic response was not observed in rabbits that had been rendered thrombocytopaenic by platelet antiserum. Induction of thrombocytopaenia by antiserum was accompanied by tachypnoea which was not significantly different (P > 0 05) from the response to emboli. The tachypnoeic response to antiserum, like that to emboli, was prevented by bilateral cervical vagotomy. Pre-treatment with aspirin (5 mg/kg), which inhibits the platelet-release reaction, also prevented the tachypnoeic response to both emboli and antiserum, although it did not prevent the fall in platelet count which followed injection of antiserum. These data support the hypothesis that the post-embolic reflex tachypnoea is platelet dependent and may be secondary to the platelet-release reaction.

5‐Hydroxytryptamine mediates the post‐embolic increase in respiratory rate in anaesthetized rabbits

“…Certainly, some metabolites of arachidonic acid (e.g. prostaglandin E2) are capable of evoking a vagally mediated tachypnoeic response, but such responses are not inhibited by MDL 72222 at the concentration used in this study (Armstrong et al 1986).…”

“…antagonized by pre-treatment with the selective neuronal 5-HT3 receptor antagonist MDL 72222 (Armstrong & Kay, 1985), we have investigated the effect of this compound on the responses evoked by pulmonary embolization. A preliminary account of this work has been presented to the Physiological Society (Armstrong, Kay & Russell, 1986).…”

MDL 72222 (a selective 5‐HT3 receptor antagonist) prevents stimulation of intrapulmonary C fibres by pulmonary embolization in anaesthetized rabbits

“…Since 5-HT is of primary importance in mediating the reflex tachypnoea evoked with the current model of embolism (Armstrong et al 1986), the effect of embolization on the discharge frequency of intrapulmonary C fibres was investigated. The effect of injection of Sephadex G-25 beads (1 mg min-', fifteen injections per animal) was investigated upon four pulmonary C fibres (conduction velocities 1-0-2-0 m s-1).…”

“…We have previously demonstrated that miliary pulmonary embolism, like the administration of intravenous 5-hydroxytryptamine (5-HT), produces vagally mediated tachypnoea which is virtually abolished by pre-treatment with the selective 5-HT3 receptor antagonist MDL 72222 (Armstrong, Kay & Russell, 1986). The vagally mediated tachypnoea could conceivably arise from stimulation of one or more of the three identified intrapulmonary sensory receptors, i.e.…”

Reflex circulatory collapse following intrapulmonary entrapment of activated platelets: mediation via 5‐HT3 receptor stimulation

“…The site of action of the 5-HT3 antagonism in the prevention of the systemic effects of 5-HT released in the lung is not centrally located, as MDL-72222 did not interfere with the hypotension induced by cephalic vagal stimulation. Indeed, the presence of 5-HT3 receptors in the so called juxta-pulmonary capillarynerve terminals has been reported (McQueen, 1990) and their stimulation is followed by bradycardia and hypotension in rabbits (Thoren, 1979;Armstrong et al, 1986). Although we cannotexclude arole forplateletactivationoutsidethelunginour experiments it is reasonable to assume that the vast majority of activated platelets are trapped in the pulmonary circulation (Hechtman, 1978).…”