Impact of inhaled nitric oxide on platelet aggregation and fibrinolysis in rats with endotoxic lung injury. Role of cyclic guanosine 5'-monophosphate.
As inhaled nitric oxide (iNO) may differently increase bleeding time (BT) and inhibit platelet aggregation in normal and lung-injured patients or experimental models, we studied the effects of iNO on hemostasis in presence and absence of an endotoxic lung injury in the rat. Eight hours after intratracheal administration of endotoxin (lipopolysaccharide [LPS]) or its solvent (phosphate-buffered solution [PBS]), four groups of rats were randomized according to the presence or absence of 15 ppm iNO added for an additional 10 h. We measured BT, ex vivo platelet aggregation, plasma fibrinogen, euglobulin clot lysis time (ECLT), and platelet and aortic cyclic guanosine 5'-monophosphate (cGMP) contents. Acute lung inflammation did not influence BT, but increased platelet aggregability, fibrinogen levels, and platelet and aortic cGMP. In control and endotoxic rats, iNO increased BT, reduced platelet aggregability, and increased platelet cGMP. iNO increased aortic cGMP only in healthy rats. ECLT was increased by LPS and unchanged with iNO. These results suggest that the extrapulmonary "systemic" effects induced by iNO on hemostasis were not strictly similar in healthy and LPS rats, inflammation inducing proper changes in coagulation parameters. However, iNO attenuated the procoagulant activity induced by acute lung inflammation, suggesting a potentially beneficial effect of this therapy.
Kermarrec
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N
Department of Anesthesiology and Critical Care Medicine, and Department of Hematology, Unité d'Enseignement et de Recherche de Médecine Lariboisière-Saint-Louis, Université Paris VII, Paris, France.
Zunic
P
P
Beloucif
S
S
Benessiano
J
J
Drouet
L
L
Payen
D
D
D000280:Administration, Inhalation; D000818:Animals; D001011:Aorta / Q000737:chemistry; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000737:chemistry; D002021:Buffers; D006152:Cyclic GMP / Q000032:analysis / Q000097:blood / Q000502:physiology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000009:adverse effects*; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006487:Hemostasis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D002021:Buffers; D004731:Endotoxins; D005343:Fibrinolytic Agents; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D005340:Fibrinogen; D006152:Cyclic GMP