[Role of serotonin in impaired gas exchange during pulmonary embolism].
Although serotonin has been reported to play a substantial role in cardiopulmonary dysfunction, the quantitative effects of serotonin, released from activated platelets, on the development of alveolar flooding and on impaired gas exchange in pulmonary embolism have not been systematically investigated. To elucidate the effects of serotonin on pulmonary hemodynamics, accumulation of edema fluid in alveolar space, and impairment of gas exchange in acute pulmonary embolism, 20 mongrel dogs were given 0.4-0.6 g/kg of glass beads with a diameter of 100 microns, via the internal jugular vein. Before and after embolization, pulmonary hemodynamics, systemic hemodynamics, blood gases, and the distribution of ventilation-perfusion ratios (VA/Q) in the lung were measured, with and without a newly developed selective antagonist of the serotonin S2 receptor, DV-7028. VA/Q distribution was determined by applying the multiple inert gas elimination technique. After glass-bead embolization, the animals that did not receive DV-7028 showed significant increases in pulmonary arterial pressure and in extravascular lung water, widened alveolar-arterial O2 tension differences, and appreciable development of low VA/Q areas (0 < VA/Q < or = 0.1). These changes were prevented in the animals that received DV-7028. However, DV-7028 did not affect the formation of high VA/Q areas (VA/Q > 10). In conclusion, in acute canine pulmonary embolism serotonin not only induces pulmonary hypertension and pulmonary edema, but also worsens gas exchange through the formation of low VA/Q areas.
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
A
A
Kawai
A
A
Umeda
M
M
Mori
T
T
Takasugi
K
K
Asano
T
T
Tanaka
M
M
Yasuoka
K
K
Yamaguchi
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D015633:Extravascular Lung Water / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011655:Pulmonary Embolism / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
D010880:Piperidines; D012702:Serotonin Antagonists; D014227:Triazines; C073727:DV 7028; D012701:Serotonin