Hypotension caused by extracorporeal circulation: serotonin from pump-activated platelets triggers nitric oxide release.
BACKGROUND
Cardiopulmonary bypass and hemodialysis often cause hypotension. We investigated a possible role of pump-induced platelet activation with consequent serotonin release.


RESULTS
In rats, a heparin-coated extracorporeal shunt was placed between the proximal part of a carotid artery and the distal part of a femoral artery. Autoperfusion did not affect platelets or hemodynamics. Pump perfusion, however, immediately elicited strong platelet aggregation, whereas aortic pressure rapidly fell to 60+/-12% (mean+/-SD) of its prepump value, partially recovered, and then progressively decreased to 70+/-12% at 2 hours. Femoral resistance doubled and then decreased to 59+/-11%. The initial changes in aortic pressure and femoral resistance were proportional to the amount of platelet aggregation, were accompanied by a rise (6-fold) in plasma serotonin levels downstream of the pump, but not in the aorta, and could be mimicked by serotonin-infusion into the leg. All hemodynamic changes were prevented or largely reduced by blockade of 5-hydroxytryptamine (5-HT)2 receptors with pizotifen or ritanserin. The hypotension and femoral resistance decrease could also be prevented or abolished by inhibiting the production of nitric oxide (NO), an intermediate in 5-HT(2B) receptor-induced vasodilation. When the extracorporeal blood was pumped into the aortic arch instead of the femoral artery, the hypotensive effect was similar and also NO dependent, but it was absent with venous return.


CONCLUSIONS
Pump perfusion with arterial return of the blood causes hypotension by endothelial NO-release, which in turn is triggered by serotonin from activated platelets.
Borgdorff
Piet
P
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. p.borgdorff.physiol@med.vu.nl
Fekkes
Durk
D
Tangelder
Geert Jan
GJ
D000818:Animals; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D007022:Hypotension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007260:Infusion Pumps; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014655:Vascular Resistance
D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D012701:Serotonin; D019001:Nitric Oxide Synthase