Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury

1 Department of Anesthesia and Critical Care, 2 Cardiovascular Research Center, 3 Cardiac Ultrasound Laboratory, Division of Cardiology, Department of Medicine, and 4 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and 5 Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Submitted 7 November 2005 ; accepted in final form 20 January 2006 To learn whether nitric oxide (NO) inhalation can decrease myocardial ischemia-reperfusion (I/R) injury, we studied a murine model of myocardial infarction (MI). Anesthetized mice underwent left anterior descending coronary artery ligation for 30, 60, or 120 min followed by reperfusion. Mice breathed NO beginning 20 min before reperfusion and continuing thereafter for 24 h. MI size and area at risk were measured, and left ventricular (LV) function was evaluated using echocardiography and invasive hemodynamic measurements. Inhalation of 40 or 80 ppm, but not 20 ppm, NO decreased the ratio of MI size to area at risk. NO inhalation improved LV systolic function, as assessed by echocardiography 24 h after reperfusion, and systolic and diastolic function, as evaluated by hemodynamic measurements 72 h after reperfusion. Myocardial neutrophil infiltration was reduced in mice breathing NO, and neutrophil depletion prevented inhaled NO from reducing myocardial I/R injury. NO inhalation increased arterial nitrite levels but did not change myocardial cGMP levels. Breathing 40 or 80 ppm NO markedly and significantly decreased MI size and improved LV function after ischemia and reperfusion in mice. NO inhalation may represent a novel method to salvage myocardium at risk of I/R injury. myocardial infarction; cardiac injury; murine model Address for reprint requests and other correspondence: M. Scherrer-Crosbie, Cardiac Ultrasound Laboratory, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114 (e-mail: marielle{at}crosbie.com )