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J Am Coll Cardiol. 2007 Aug 21;50(8):808-17. Epub 2007 Aug 6.

Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion.

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1
Department of Cardiology, University of Leuven, Leuven, Belgium.

Abstract

OBJECTIVES:

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.

PMID:
17707188
DOI:
10.1016/j.jacc.2007.04.069
[Indexed for MEDLINE]
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