Inhaled nitric oxide does not influence bleeding time or platelet function in healthy volunteers

SummaryThe platelet inhibitory effect of 0-40 ppm inhaled nitric oxide (NO) was investigated in healthy men and women. In both groups, ADPand collagen-induced platelet aggregation was significantly inhibited 20 (T20) and 40 min (T40) after the beginning of inhalation of 5, 10, and 40 ppm. Moreover, in both men and women, the in vitro bleeding time was significantly prolonged at T20 and T40 during inhalation of 40 ppm. Inhalation of NO also inhibited P-selectin expression at 5, 10, and 40 ppm and fibrinogen binding to the GPIIb/IIIa-receptor at 40 ppm. In conclusion, in healthy volunteers, the platelet inhibitory effect of inhaled NO was not dose-related, since it was significant at 5 and 10 ppm but did not increase during the administration of higher NO concentrations. In addition, gender-related differences were only observed in ADP-induced platelet aggregation at 10 ppm and in bleeding time prolongation at 40 ppm.

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Effects of Inhaled Nitric Oxide Compared with Aspirin on Platelet Function in Vivo in Healthy Subjects

Clinical Science ◽

10.1042/cs0910225 ◽

1996 ◽

Vol 91 (2) ◽

pp. 225-231 ◽

Cited By ~ 23

Author(s):

Johanna Albert ◽

N. Håkan Wallén ◽

Anders Bröijersén ◽

Claes Frostell ◽

Paul Hjemdahl

Keyword(s):

Nitric Oxide ◽

Platelet Function ◽

Healthy Subjects ◽

Bleeding Time ◽

Ex Vivo ◽

Inhaled Nitric Oxide ◽

Platelet Aggregability ◽

Nitric Oxide Inhalation ◽

Platelet Secretion

1. Nitric oxide has platelet-stabilizing effects. Inhaled nitric oxide is used to treat pulmonary disorders, and may prolong bleeding times, suggesting that it has effects on haemostasis. We therefore examined if inhaled nitric oxide influences platelet function in vivo in healthy subjects. 2. Platelet aggregability (filtragometry ex vivo, which reflects aggregability in vivo), bleeding time and platelet secretion products and cGMP in plasma were studied during inhalation of two different doses of nitric oxide (30 and 80 p.p.m.; 15 min at each dose level; n = 19) and during prolonged (55 min; n = 18) inhalation of 30p.p.m. nitric oxide. For comparison, studies were also performed before and after ingestion of 640 mg aspirin in 13 of the healthy subjects. 3. Plasma cGMP increased dose dependently during nitric oxide inhalation, suggesting guanylate cyclase activation in vivo. Platelet aggregability was, however, little affected and platelet secretion was not attenuated by nitric oxide inhalation. Bleeding time tended to increase (by 16–33%), but was significantly increased only after prolonged inhalation of nitric oxide at 30 p.p.m. 4. Aspirin (640 mg orally) caused pronounced and significant prolongations of filtragometry readings and bleeding time. Thus, the methods used were able to reveal platelet stabilization. 5. We conclude that nitric oxide inhalation causes only mild, if any, attenuation of platelet function in healthy subjects with a normal endogenous nitric oxide production. The effects may be different in disease states.

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Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers

Clinical Science ◽

10.1042/cs0970345 ◽

1999 ◽

Vol 97 (3) ◽

pp. 345-353 ◽

Cited By ~ 9

Author(s):

Johanna ALBERT ◽

N. Håkan WALLÉN ◽

Nailin LI ◽

Claes FROSTELL ◽

Paul HJEMDAHL

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Heart Rate ◽

Healthy Volunteers ◽

Thrombin Generation ◽

Bleeding Time ◽

Flow Cytometric ◽

Fibrinogen Binding ◽

Inhaled No

Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by NG-monomethyl-⌊-arginine (⌊-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, ⌊-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of ⌊-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma β-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin–antithrombin complexes) in plasma, and bleeding time. l-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P < 0.001). Neither ⌊-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma β-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by ⌊-NMMA compared with placebo, but was increased by ≈ 25% during NO inhalation (P < 0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.

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Inhibition of Platelet Aggregation by Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome

Anesthesiology ◽

10.1097/00000542-199507000-00007 ◽

1995 ◽

Vol 83 (1) ◽

pp. 56-65. ◽

Cited By ~ 146

Author(s):

Charles Marc Samama ◽

Mohamed Diaby ◽

Jean-Luc Fellahi ◽

Ayoub Mdhafar ◽

Daniel Eyraud ◽

...

Keyword(s):

Nitric Oxide ◽

Acute Respiratory Distress Syndrome ◽

Platelet Aggregation ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Bleeding Time ◽

Distress Syndrome ◽

Inhaled Nitric Oxide ◽

Arterial Oxygenation ◽

Inhibition Of Platelet Aggregation

Background Nitric oxide inhibits platelet adhesion and aggregation in vitro. The aim of this prospective study was to assess the platelet antiaggregating activity of nitric oxide administered to patients with acute respiratory distress syndrome (ARDS) at increasing concentrations. Methods In six critically ill patients (mean age 37 +/- 16 yr) with ARDS (lung injury severity score > or = 2.2), the lungs were mechanically ventilated with inhaled nitric oxide (1, 3, 10, 30, and 100 ppm) randomly administered. Patients with cardiac dysrhythmias, septic shock, an underlying hemostasis disorder (constitutive or acquired), a platelet count less than 100 Giga/l, or a decreased platelet aggregation and those treated with antiplatelet or anticoagulant agents were excluded. Platelet aggregation was measured without nitric oxide and at each nitric oxide concentration in platelet-rich plasma issued from radial artery. Ivy bleeding time using a horizontal incision was simultaneously performed. Results After nitric oxide, a non-dose-dependent but statistically significant decrease in ex vivo platelet aggregation induced by three aggregating agents was observed: adenosine diphosphate = -56 +/- 18%, collagen = -37 +/- 18%, and ristocetin = -45 +/- 18% (P < 0.05). In each individual, Ivy bleeding time remained within normal values measured in healthy volunteers, and variations after nitric oxide did not correlate with changes in platelet aggregation. Simultaneously, arterial oxygenation improved significantly and pulmonary artery pressure decreased significantly. Conclusions In patients with ARDS and without preexisting coagulation disorders, the beneficial effects of inhaled nitric oxide on arterial oxygenation and pulmonary circulation are associated with a significant inhibition of platelet aggregation. This antithrombotic effect is not associated with a significant prolongation of the bleeding time.

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