INHALED NITRIC-OXIDE INHIBITS PLATELET-AGGREGATION AFTER PULMONARY-EMBOLISM IN PIGS

Background: Inhaled nitric oxide (NO) is reported to prolong bleeding time in animals and humans and to inhibit platelet aggregation in pers ons with acute respiratory distress syndrome. In pulmonary embolism (P E), inhibition of platelet aggregation appears useful because further thrombus formation may lead to right ventricular dysfunction that resu lts in circulatory failure, In the present study, the effect of inhale d NO on platelet aggregation after acute massive PE was investigated. Methods: After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled N O were administered stepwise for 10 min each in 11 animals (NO group), In the control group (n = 14), NO was not administered, Adenosine dip hosphate-induced initial and maximal platelet aggregation were measure d before PE (t0), immediately after induction of PE (PE), at the end o f each 10-min NO inhalation interval (t10-t40), and 15 min after cessa tion of NO inhalation (t55) in the NO group, and at corresponding time s in the control group, respectively. Results: Two animals in the cont rol group and one in the NO group died within 10 min after PE inductio n and were excluded from analysis. Peaking at t40 and t55, respectivel y, initial (+13 +/- 6%; P < 0.05) and maximal (+44 +/- 17%; P < 0.05) platelet aggregation increased significantly after PE in the control g roup. In contrast, NO administration after PE led to a significant dec rease in initial (maximum decrease, -9 +/- 3% at t40; P < 0.05) and ma ximal (maximum decrease, -15 +/- 7% at t30; P < 0.05) platelet aggrega tion, In the NO group, platelet aggregation had returned to baseline l evels again at t55. In addition, NO administration significantly decre ased mean pulmonary artery pressure and significantly increased end-ti dal carbon dioxide concentration and mean systemic blood pressure. Con clusions: Inhaled NO has a systemic and rapidly reversible inhibitory effect on platelet aggregation after acute massive PE in pigs, This ma y be beneficial in treating acute massive PE.