Vasodilation by shear-induced platelet aggregation in extracorporeal circuits.
Extracorporeal circulation may have adverse effects on vascular reactivity. To reduce such effects, we recently coated a tube connecting the carotid and the distal femoral artery of rats with albumin. When we partially occluded this perfusion line, the reduction of flow was followed by a marked increase, which seemed not to be caused by autoregulation but by release of a vasodilator at the site of occlusion. In the present study, we investigated whether this vasodilator could originate from platelets aggregating under the influence of increased shear stress at the site of occlusion. Blood distal to the site of occlusion indeed contained numerous platelet aggregates that were not present before occlusion. Continuous recording with a photometric device showed that aggregation in the tube started before flow increased and ended before flow decreased again. Blockade of serotonin S1- and S2-receptors with methiothepin prevented the flow response. Estimated shear stress (231 +/- 17 dyn/cm2) and shear rate (6,370 +/- 478 s-1) at the site of occlusion were of the magnitude known to elicit platelet aggregation. Others have recently demonstrated that shear-induced platelet aggregation is mediated by binding of von Willebrand factor to platelet glycoprotein Ib, which is inhibited by aurintricarboxylic acid. This drug (35 mg/kg iv) completely abolished both platelet aggregation and flow increase in our experiments. These results suggest that the vasodilation during partial tube occlusion is mediated by serotonin released from platelets that aggregate as a result of high shear stress.
Borgdorff
P
P
Laboratory for Physiology, Free University, Amsterdam, The Netherlands.
Kok
W E
WE
Vis
M A
MA
van den Bos
G C
GC
D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002339:Carotid Arteries / Q000502:physiology; D005112:Extracorporeal Circulation; D005263:Femoral Artery / Q000502:physiology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D010974:Platelet Aggregation; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D013314:Stress, Mechanical; D014664:Vasodilation
D012702:Serotonin Antagonists; D001312:Aurintricarboxylic Acid; D008719:Methiothepin