[Show abstract][Hide abstract] ABSTRACT: In order to investigate if decompression sickness involves platelet activation an animal model was evaluated.
Twenty-four thiopentone-midazolam-fentanyl-anaesthetized pigs in four groups received 5-min infusions of adenosine diphosphate (25 mg/kg) or platelet activating factor (0.4 microg/kg). Groups 1 and 2 (adenosine diphosphate, n=6 and platelet activating factor, n=6) were studied for 30 min and then sacrificed. Groups 3 and 4 (adenosine diphosphate, n=6 and platelet activating factor, n=6) were sacrificed immediately afterwards to study short-term changes. Haemodynamics, platelet counts and post mortem lung platelet aggregates were registered. Groups 1 and 2 also had indium platelet labelling, lung scintigraphy and platelet accumulation index calculations performed.
Adenosine diphosphate induced immediate and more profound transient shocks. Platelet and leukocyte count decreases and occurrences of post mortem lung platelet aggregates were significantly more profound in the 5-min adenosine diphosphate group (Group 3) than in the platelet activating factor group (Group 4). With platelet labelling there were positive platelet accumulation index trends in the 30-min adenosine diphosphate group (Group 1). Adenosine diphosphate also produced platelet aggregation in platelet-rich porcine plasma. Only adenosine diphosphate (an intermediate platelet agonist) showed signs of platelet activation when considering all platelet parameters. The model should be further evaluated with different bolus doses of adenosine diphosphate, but may be used to evaluate if gas bubbles introduced into the circulation (as with decompression sickness), or possibly if clinical drugs, might produce platelet activation in vivo.
Full-text · Article · Feb 2006 · Thrombosis Research
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of decompression illness (DCI) is uncertain. DCI involves all parts of the organism where gas bubbles are produced. They have both primary and secondary effects and have been classified as an agonist aggregating human platelets. In vitro effects of N2 bubbles on porcine platelets were investigated. Comparative studies using two different anticoagulants and three different sampling methods were performed. A disappearance of single platelets interpreted as platelet aggregation was observed in the presence of N2 bubbles in all studied groups. Aggregatory responses were more profound with platelets in heparinized plasma than in citrated plasma. In citrated plasma the aggregatory responses were more profound when blood was obtained from nonanaesthetized (awake) animals than from slaugtherhouse animals. Adrenaline (1 microM) had an inhibitory effect on N2 bubble induced platelet aggregation in vitro. The pig could be useful to investigate possible gas bubble effects in vivo.
Full-text · Article · Nov 1994 · Thrombosis Research
[Show abstract][Hide abstract] ABSTRACT: The effect of nitrogen (N(2))-microbubbles on human platelets resembles that of common agonists in terms of aggregation, but displays one unusual feature in that cyclooxygenase-inhibitors (e.g. aspirin) poorly inhibit the reaction. In the present study, we have investigated the cyclooxygenase-dependence of microbubble-induced platelet secretion of β-thromboglobulin (β-TG) and (14)C-serotonin. The effect of microbubbles in stirred platelet-rich plasma (PRP) was compared with that of collagen and of polystyrene microspheres. The reduction in the number of single platelets induced by microbubbles was continuous with time and reached 60% after 30 min and was accompanied by secretion of (14)C-serotonin and β-TG. While 50% of the secretion of β-TG persisted in spite of aspirin treatment, secretion of (14)C-serotonin was completely abolished. The enhancing effect of epinephrine on microbubble-induced platelet secretion appeared to be prostanoid dependent. Platelet secretion of β-TG and (14)C-serotonin induced by a high dose of collagen was significantly reduced by aspirin, while a low dose of collagen induced a cyclooxygenase-independent secretion of β-TG and (14)C-serotonin. The reduction in single platelets when PRP was stirred with microspheres reached a mean value of 27% after 10 min but did not increase further with time. Microspheres caused a small but significant secretion of β-TG but no secretion of (14)C-serotonin. Aspirin did not reduce the loss in single platelets nor the secretion of β-TG. The present study suggests that cyclooxygenase independent α-granule secretion may facilitate and, at least in part, sustain the reaction between microbubbles and platelets. The difference in agonistic effect of polystyrene microspheres on platelets shows that polystyrene spheres are not suitable substitutes for microbubbles in in vitro or in vivo experiments.
[Show abstract][Hide abstract] ABSTRACT: The effect of nitrogen-(N2-)microbubbles on platelets resembles that of common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This paper reports the effect of microbubbles on platelet phospholipase C activity in gelfiltered human platelets prelabelled with [32P]Pi ([32P]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADP. Stimulation of [32P]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p < 0.0004) and a significant increase in 32P-activity in the phosphatidic acid (PA) fraction (p < 0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p < 0.05), but did not enhance the amount of 32P in the platelet [32P]PA fraction. The 32P-radioactivity in the PI-fraction increased with time to a similar extent when [32P]-GFP was stirred for 30 min in absence of microbubbles as it did after 30 min of agonist exposure. There were no significant changes in the [32P]PIP and [32P]PIP2 fractions. Aspirin abolished the microbubble-induced increase in 32P-activity in the PA fraction, but had no significant effect on the reduction in single platelets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles (p < 0.05). With epinephrine, however, aspirin did not completely abolish the increase in [32P]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates independent of cyclooxygenase-dependent arachidonic acid metabolites and phospholipase C activation.
No preview · Article · Apr 1993 · Thrombosis and Haemostasis