Chronic intermittent asphyxia increases platelet reactivity in rats

Abstract

Sleep-disordered breathing is associated with chronic intermittent asphyxia and with a variety of cardiovascular abnormalities. Cardiovascular morbidity and mortality are linked to altered platelet function, and platelet function is affected in sleep-disordered breathing. As there is evidence that chronic continuous hypoxia may alter platelet number and function, the aim of the present study was to test the hypothesis that chronic intermittent asphyxia affects platelet count, activation and aggregation. Rats were treated with a hypercapnic hypoxic gas mixture (minimum of 6-8% O 2 , maximum of 10-14% CO 2 ) for 15 s, twice per minute for 8 h per day for 3 weeks. Blood was analysed for platelet count, platelet activation (CD62p expression using flow cytometry), response to low dose ADP, haematocrit, red cell count and haemoglobin concentration. A platelet function analyser measured the closure time of an aperture, dependent on platelet aggregation. Compared to controls (n = 16), chronic intermittent asphyxia (n = 13) reduced body weight and increased right ventricular weight but had no significant effect on platelet count (control, 880.4 ± 20.1; treated: 914.1 ± 35.2 × 10 3 µl −1 ; mean ± S.E.M.), on the reduction in platelet count in response to ADP (control, reduced to 206.7 ± 49.0; treated, reduced to 193.8 ± 35.9 × 10 3 µl −1 ), or on the percentage of platelets positive for CD62p (control, 5.2 ± 0.7; treated, 6.0 ± 0.8%). Chronic intermittent asphyxia significantly (P = 0.037) reduced the closure time (control, 90.9 ± 7.7; treated, 77.7 ± 3.8 s), indicating greater adhesion and aggregation. There was no significant difference in haematocrit, red cell count and haemoglobin concentration. In conclusion, chronic intermittent asphyxia has no effect on platelet count but does increase platelet aggegation in rats. These data support the idea that chronic intermittent asphyxia alters platelet function in sleep-disordered breathing. Sleep-disordered breathing is characterized by intermittent apnoea caused by intermittent upper airway obstruction, called obstructive sleep apnoea, or by an intermittent reduction in respiratory drive called central sleep apnoea. Each episode of apnoea can result in progressive asphyxia (Alford et al. 1986) which leads eventually to arousal and restoration of upper airway patency (Remmers et al. 1978). As these episodes of apnoea occur many times during the course of sleep, the condition is associated with chronic intermittent asphyxia (CIA). We have developed a rat model which mimics the blood gas changes associated with human sleep-disordered breathing (McGuire & Bradford, 1999, 2001 McGuire et al. 2002a,b;O'Halloran et al. 2002). In the present study, we used CIA whereas we and others have also used chronic intermittent hypoxia (CIH) as a model of sleep apnoea. This is because apnoeic periods are accompanied by either hypoxia with little change in CO 2 levels or by hypoxia along with hypercapnia, i.e. asphyxia. In fact, the CIH model has the disadvantage that the hypoxia is actually a...

Impact of Nasal Continuous Positive Airway Pressure Therapy on Markers of Platelet Activation in Patients with Obstructive Sleep Apnea

“…Taken together, these data suggest that hypoxia may mediate platelet activation. Whether this reaction occurs as a result of increased activation of the sympathetic pathway [27] or as a direct effect of chronic intermittent hypoxia [28], evidence suggests that upon platelet activation, CD40L becomes expressed on the platelet surface which is then cleaved over a period of minutes to hours, generating the soluble fragment sCD40L [29]. Upon binding to CD40, several inflammatory processes are initiated, including the expression of cytokines, chemokines, growth factors and adhesion molecules [30, 31] that are integral components to the progression of atheromas.…”

Possible Role of Lysophosphatidic Acid in Rat Model of Hypoxic Pulmonary Vascular Remodeling

“…Hypoxia per se may accelerate blood coagulation 5 and platelet adhesion and aggregation. 6 The activation of platelets can result in the release of multiple and diverse soluble mediators such as interleukin-1, bioactive lipids, and chemokines with pleiotropic functions in inflammation. 7,8 Platelets play a key role in thrombosis and inflammation, and several studies indicate a survival benefit in anticoagulated idiopathic PH patients.…”

“…Hypoxia per se may accelerate blood coagulation 5 and platelet adhesion and aggregation. 6 The activation of platelets can result in the release of multiple and diverse soluble mediators such as …”

Continuous Positive Airway Pressure and Platelet Activation in Obstructive Sleep Apnoea

“…Chronic continuous hypoxia is known to cause an early thrombocytosis and a subsequent thrombocytopaenia. In just one study, chronic intermittent asphyxia in rats had no effect on platelet number [11] .…”

“…It is well known that chronic continuous hypoxia can cause changes in coagulation and in platelet number and function [9] and that changes in platelet function are associated with adverse cardiovascular effects [10] . Recently, it has been shown in rats that platelet activation can occur also when the hypoxia is intermittent [11] . Taken together, this provides good reason to suspect that alterations in platelet function as a consequence of the intermittent hypoxia of sleep apnoea may underlie some of the adverse cardiovascular effects associated with the condition.…”