Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury.
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.
Hataishi
Ryuji
R
Department of Anesthesia and Critical Care, Massachusetts General Hospital and Havard Medical School, Boston, MA 02114, USA.
Rodrigues
Ana Clara
AC
Neilan
Tomas G
TG
Morgan
John G
JG
Buys
Emmanuel
E
Shiva
Sruti
S
Tambouret
Rosemary
R
Jassal
Davinder S
DS
Raher
Michael J
MJ
Furutani
Elissa
E
Ichinose
Fumito
F
Gladwin
Mark T
MT
Rosenzweig
Anthony
A
Zapol
Warren M
WM
Picard
Michael H
MH
Bloch
Kenneth D
KD
Scherrer-Crosbie
Marielle
M
D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D009569:Nitric Oxide / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*
D009569:Nitric Oxide