Inhaled nitric oxide inhibits the release of matrix metalloproteinase-2, but not platelet activation, during extracorporeal membrane oxygenation in adult rabbits.
OBJECTIVE
In neonates receiving extracorporeal membrane oxygenation (ECMO), platelet activation and dysfunction occur with the release of matrix metalloproteinase (MMP)-2, which stimulates platelet aggregation. Because inhaled nitric oxide (NO) reduces pulmonary hypertension and inhibits platelet aggregation, the authors examined the effects of inhaled NO on platelet activation induced by ECMO.


METHODS
Ten adult white New Zealand rabbits were instrumented for ECMO and assigned randomly to receive either inhaled NO at 40 ppm or 30% oxygen for 1 hour before ECMO and continued for 4 hours after starting ECMO. Platelet counts, collagen-induced platelet aggregation ex vivo, plasma MMP-2, and MMP-9 activities were measured.


RESULTS
(1) ECMO caused thrombocytopenia, decreased platelet aggregation, and increased plasma MMP-2 and MMP-9 activities in controls. (2) Inhaled NO inhibited platelet aggregation before ECMO but did not affect the ECMO-induced thrombocytopenia and platelet activation. (3) Inhaled NO significantly abolished the ECMO-induced increase in plasma MMP-2 but not MMP-9 activities.


CONCLUSIONS
Although inhaled NO did not inhibit the platelet activation during ECMO in adult rabbits, it attenuated the increase in plasma MMP-2 activity that may be important for neonates treated with ECMO.
Cheung
P-Y
PY
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Sawicki
G
G
Peliowski
A
A
Etches
P C
PC
Schulz
R
R
Radomski
M W
MW
D000280:Administration, Inhalation; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010100:Oxygen / Q000097:blood / Q000494:pharmacology; D010313:Partial Pressure; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012131:Respiratory Insufficiency / Q000628:therapy; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology
D002245:Carbon Dioxide; D009569:Nitric Oxide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010100:Oxygen