Reflex circulatory collapse following intrapulmonary entrapment of activated platelets: mediation via 5-HT3 receptor stimulation.
1. The role of 5-HT2 and 5-HT3 receptors in the mediation of direct and reflex vascular responses to intrapulmonary platelet activation was investigated. 2. Anaesthetized rabbits were challenged intravenously with an emulsion of autologous bone marrow that produced a sharp increase in pulmonary blood pressure, a fall in systemic blood pressure, platelet consumption and death. 3. Platelet depletion before the challenge nearly abolished all the cardiovascular effects and prevented death. Bilateral vagotomy prevented the fall in systemic blood pressure and death but did no prevent the increase in pulmonary pressure. The intravenous administration of the 5-HT2 antagonist, ketanserin, only reduced the increase in pulmonary pressure without affecting the systemic response or mortality. 4. The effects of intravenous 5-HT and of electrical stimulation of the cephalic ends of the cut vagi nerves were also explored. 5-HT injection increased the pulmonary vascular pressure but its effects on systemic blood pressure were variable. These response were modified by the 5-HT antagonists in a manner that resembles their effects on bone marrow embolism. Afferent vagal stimulation produced a fall in systemic blood pressure that was not prevented by MDL-7222. 5. This study indicates that a centrally mediated reduction of peripheral vascular tone is the cause of the potentially lethal circulatory collapse that follows the intrapulmonary entrapment of activated platelets. This reflex is initiated by the action of 5-HT on 5-HT3 receptors in the lung.
Leaños
O L
OL
Military Graduate School for the Health Sciences, Mexico City, Mexico.
Hong
E
E
Amezcua
J L
JL
D000818:Animals; D016026:Bone Marrow Transplantation; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011817:Rabbits; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D014326:Tropanes / Q000008:administration & dosage / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D014326:Tropanes; C042253:bemesetron