Inhaled nitric oxide increases coronary artery patency after thrombolysis.
BACKGROUND
Nitric oxide (NO) and nitrosovasodilators that release NO inhibit platelet aggregation. The antithrombotic effect of intravenously infused nitrosovasodilators is usually accompanied by systemic vasodilation. Inhaled NO is a pulmonary vasodilator that does not produce systemic hemodynamic effects. This study examines the antithrombotic effect of inhaled NO in a canine model of platelet-mediated coronary artery reocclusion after thrombolysis.


RESULTS
In 25 anesthetized dogs, a segment of the left anterior descending coronary artery was traumatized and a high-grade stenosis created. Thrombus was injected at this site, and tissue plasminogen activator was administered, producing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency was unchanged in dogs not breathing NO but decreased by 35 +/- 9% (P < .05) and 53 +/- 7% (P < .01) while dogs breathed 20 and 80 parts per million (ppm) NO, respectively. The coronary artery patency ratio (fraction of time during which the coronary artery was patent; CAPR) was unchanged in dogs not treated with NO but increased from 51 +/- 7% to 64 +/- 8% while breathing 20 ppm NO (P < .01) and from 49 +/- 3% to 75 +/- 7% while breathing 80 ppm NO (P < .01). The increased CAPR during 80 ppm NO administration persisted during a 45-minute posttreatment period (70 +/- 7%, P < .05 versus baseline). NO inhalation did not change systemic hemodynamics. In a pharmacological model of coronary vasoconstriction, inhaled NO did not reverse the effect of the thromboxane A2 agonist U-46619. In vitro ADP-induced platelet aggregation was inhibited by NO gas.


CONCLUSIONS
Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and decreases CFV frequency in a canine model of platelet-mediated coronary reocclusion after thrombolysis without producing systemic hemodynamic effects.
Adrie
C
C
Department of Anesthesia, Massachusetts General Hospital, Boston 02114, USA.
Bloch
K D
KD
Moreno
P R
PR
Hurford
W E
WE
Guerrero
J L
JL
Holt
R
R
Zapol
W M
WM
Gold
H K
HK
Semigran
M J
MJ
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D001760:Bleeding Time; D003328:Coronary Thrombosis / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D012008:Recurrence; D015912:Thrombolytic Therapy; D014654:Vascular Patency / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide; D000244:Adenosine Diphosphate