Document Detail


Therapeutic benefits of 5-hydroxytryptamine inhibition following pulmonary embolism.
MedLine Citation:
PMID:  6824376     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The smooth muscle-constricting, platelet amine, serotonin (5-hydroxytryptamine; 5-HT) is theorized to play an important role in the cardiopulmonary dysfunction that accompanies embolization. The present study was designed to examine this hypothesis. Autologous clot, 0.75 g/kg, was injected IV into 14 dogs. After 30 minutes, one half of the animals were randomly assigned to the treatment group and received a bolus infusion of 0.15 mg/kg ketanserin, a quinazoline derivative known to be a selective 5-HT receptor antagonist. Five minutes after embolization there were increases in mean pulmonary arterial pressure (MPAP) from 12 mm to 48 mmHg (p less than 0.001); pulmonary vascular resistance (PVR) from 2.2 mm to 12.2 mmHg X min/L (p less than 0.001); physiologic shunt (QS/QT) from 12% to 44% (p less than 0.01); and physiologic dead space (VD/VT), calculated from end tidal and arterial PCO2, from 8% to 39% (p less than 0.001). Within 15 minutes platelet counts decreased from 186,000/mm3 to 134,800/mm3 (p less than 0.05); 5-HT contained in circulating platelets fell from 1.71 micrograms/ to 1.44 micrograms/10(9) platelets (p less than 0.05). Five minutes after ketanserin, MPAP declined to 27 mmHg and was lower than the control value of 41 mmHg (p less than 0.05); PVR decreased to 6.2 mmHg X min/L, lower than 12 mmHg X min/L in controls (p less than 0.01); QS/QT fell to 26% in contrast to 47% in controls (p less than 0.05); and VD/VT declined moderately to 32% (p less than 0.05), although this value was not different from 38% in control animals. Cardiopulmonary function continued to improve in treated animals until termination of the experiment at four hours when pulmonary angiograms and perfusion scans demonstrated vascular recruitment compared with untreated embolized control dogs. These data demonstrate that the cardiopulmonary consequences of experimental embolization are primarily determined by the vasoconstrictive and bronchoconstrictive actions of 5-HT.
Authors:
W V Huval; M A Mathieson; L I Stemp; B M Dunham; A G Jones; D Shepro; H B Hechtman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Annals of surgery     Volume:  197     ISSN:  0003-4932     ISO Abbreviation:  Ann. Surg.     Publication Date:  1983 Feb 
Date Detail:
Created Date:  1983-03-11     Completed Date:  1983-03-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  220-5     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Dogs
Female
Ketanserin
Male
Piperidines / therapeutic use*
Platelet Count
Prostaglandins / blood
Pulmonary Embolism / drug therapy*,  physiopathology
Pulmonary Wedge Pressure / drug effects
Receptors, Serotonin / drug effects
Respiratory Dead Space / drug effects
Serotonin / blood
Serotonin Antagonists / therapeutic use*
Vascular Resistance / drug effects
Grant Support
ID/Acronym/Agency:
GM24891-05/GM/NIGMS NIH HHS; HL16715-06/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Piperidines; 0/Prostaglandins; 0/Receptors, Serotonin; 0/Serotonin Antagonists; 50-67-9/Serotonin; 74050-98-9/Ketanserin
Comments/Corrections

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