Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion.
OBJECTIVE
The purpose of this study was to test if nitric oxide (NO) could improve microvascular perfusion and decrease tissue injury in a porcine model of myocardial ischemia and reperfusion (I/R).


BACKGROUND
Inhaled NO is a selective pulmonary vasodilator with biologic effects in remote vascular beds.


METHODS
In 37 pigs, the midportion of the left anterior descending coronary artery was occluded for 50 min followed by 4 h of reperfusion. Pigs were treated with a saline infusion (control; n = 14), intravenous nitroglycerin (IV-NTG) at 2 microg/kg/min (n = 11), or inhaled nitric oxide (iNO) at 80 parts per million (n = 12) beginning 10 min before balloon deflation and continuing throughout reperfusion.


RESULTS
Total myocardial oxidized NO species in the infarct core was greater in the iNO pigs than in the control or IV-NTG pigs (0.60 +/- 0.05 nmol/mg tissue vs. 0.40 +/- 0.03 nmol/mg tissue and 0.40 +/- 0.02 nmol/mg tissue, respectively; p < 0.01 for both). Infarct size, expressed as percentage of left ventricle area at risk (AAR), was smaller in the iNO pigs than in the control or IV-NTG pigs (31 +/- 6% AAR vs. 58 +/- 7% AAR and 46 +/- 7% AAR, respectively; p < 0.05 for both) and was associated with less creatine phosphokinase-MB release. Inhaled NO improved endocardial and epicardial blood flow in the infarct zone, as measured using colored microspheres (p < 0.001 vs. control and IV-NTG). Moreover, NO inhalation reduced leukocyte infiltration, as reflected by decreased cardiac myeloperoxidase activity (0.8 +/- 0.2 U/mg tissue vs. 2.3 +/- 0.8 U/mg tissue in control and 1.4 +/- 0.4 U/mg tissue in IV-NTG; p < 0.05 for both) and decreased cardiomyocyte apoptosis in the infarct border zone.


CONCLUSIONS
Inhalation of NO just before and during coronary reperfusion significantly improves microvascular perfusion, reduces infarct size, and may offer an attractive and novel treatment of myocardial infarction.
Liu
Xiaoshun
X
Department of Cardiology, University of Leuven, Leuven, Belgium.
Huang
Yanming
Y
Pokreisz
Peter
P
Vermeersch
Pieter
P
Marsboom
Glenn
G
Swinnen
Marc
M
Verbeken
Eric
E
Santos
Jose
J
Pellens
Marijke
M
Gillijns
Hilde
H
Van de Werf
Frans
F
Bloch
Kenneth D
KD
Janssens
Stefan
S
D000280:Administration, Inhalation; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D009195:Peroxidase