Vasodilation by shear-induced platelet aggregation in extracorporeal circuits

Abstract

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.

Migraine: Possible Role of Shear‐Induced Platelet Aggregation With Serotonin Release

“…In this paper, we present an extension of the platelet hypothesis of Hanington, 5 integrating data from previously published literature with observations made in a rat model of shear stress‐induced platelet aggregation 6‐9 . Our hypothesis suggests that in a number of patients, especially those with hyperaggregable platelets, the neural and vascular symptoms of migraine are independently initiated by serotonin (5‐hydroxytryptamine, 5‐HT) released from aggregating platelets.…”

“…In our rat experiments, compression of the extracorporeal tubing caused platelet aggregation and dilation of the femoral bed that were both prevented by blocking the binding of vWf to the platelet glycoprotein Ib receptors with aurintricarboxylic acid. 6 More intense platelet aggregation, induced with aid of a roller pump on the tubing, elicited a triphasic vascular reaction as depicted in Figure 1: an initial vasodilation followed by temporary vasoconstriction and a long-lasting (hours) vasodilation. Of note, measurement of free hemoglobin in blood behind the pump showed no signs of hemolysis.…”

“…In this paper, we present an extension of the platelet hypothesis of Hanington,5 integrating data from previously published literature with observations made in a rat model of shear stress-induced platelet aggregation. [6][7][8][9] Our hypothesis suggests that in a number of patients, especially those with hyperaggregable platelets, the neural and vascular symptoms of migraine are independently initiated by serotonin (5-hydroxytryptamine, 5-HT) released from aggregating platelets.Aggregation might be elicited by increased shear stress at sites of vessel abnormalities, especially when in these patients a migraine trigger has further enhanced platelet aggregability, for example via reduction in circulating platelet antagonists like prostacyclin (PGI2). 10,11…”

Hypotension Caused by Extracorporeal Circulation

“…18 For quantification, the signals were converted to uniform spikes and counted over periods of 10 seconds. Platelet number and volume in systemic blood were determined using a Helios cell counter (ABX Diagnostics), with values being corrected for changes in hematocrit (see below).…”

Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation

“…Importantly, the effects of many of these components on cardiac electrophysiology, especially during the development of infarction, have yet to be characterised. For example, activated platelets are a source of serotonin, which can alter coronary blood flow and increase vascular permeability (Borgdorff et al ., 1994), complement accumulation within infarcting tissue (Rossen et al ., 1985; Crawford et al ., 1988) can trigger mast cell degranulation and histamine release (Frangogiannis et al ., 1998; 2002), mast cells are also a source of leukotrienes and prostaglandins (Gordon et al ., 1990), and there are also a number of other chemoattractant substances, such as leukotriene B 4 (Sasaki et al ., 1988), PAF (Annable et al ., 1985; Flores et al ., 1994) and the interleukin IL‐8 and IL‐6 (Kukielka et al ., 1995a, 1995b), which are present within the infarcting tissue and are putative mediators of phase 2 VF. It is also possible that inflammatory substances shown to predict risk of adverse coronary events, such as C‐reactive protein and Lp‐PLA 2 (Biasucci, 2004; Oei et al ., 2005), may have an arrhythmogenic propensity.…”