MYOCARDIAL ISCHEMIA AND INFARCTION

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A115.E1079 JACC March 9, 2010 Volume 55, issue 10A

MYOCARDIAL ISCHEMIA AND INFARCTION

DOWNREGULATION OF CARDIAC MYOGLOBIN MAY LIMIT THE CARDIOPROTECTIVE EFFECTS OF NITRITE THERAPY FOLLOWING EXERCISE

ACC Poster Contributions Georgia World Congress Center, Hall B5 Monday, March 15, 2010, 9:30 a.m.-10:30 a.m.

Session Title: Mechanisms of Ischemic Injury and Protection Abstract Category: Myocardial Ischemia/Infarction--Basic Presentation Number: 1157-293

Authors: Chad K. Nicholson, Juan Pablo Aragon, David Bennett Grinsfelder, Marah Elston, David J. Lefer, John W. Calvert, Emory University School of Medicine, Atlanta, GA

Background: Dietary nitrite supplementation provides robust protection against acute myocardial ischemia-reperfusion (MI/R) injury in animal models by increasing systemic nitrite and nitrosothiols levels. Here, we investigated if the combination of nitrite supplementation and exercise training could provide a synergistic effect to reduce infarction in a murine model of MI/R.

Methods: A group of mice were allowed to exercise voluntarily for 4 wks (VE), whereas control mice remained sedentary (SED) for 4 wks. Additionally, groups of SED and VE mice were supplemented with sodium nitrite (NO2, 25 mg/L) in their drinking water for 4 wks. Following 4 wks of VE and nitrite supplementation, mice were subjected to 45 min of in vivo myocardial ischemia followed by 24 hr of reperfusion, at which time myocardial area-at-risk (AAR) per left ventricle (LV) and infarct size per AAR (INF/AAR) were evaluated.

Results: VE reduced the INF/AAR by 18% (p < 0.05 vs. SED), whereas nitrite alone reduced INF/AAR by 53% (p < 0.05 vs. SED). Surprisingly, the combination of VE and nitrite (VE+NO2 4 wks) only reduced INF/AAR to same extent as VE alone (18%; p < 0.05 vs. SED). Interestingly, the protein expression of the nitrite reductase, myoglobin, was decreased in the heart of VE mice, suggesting that there is dysfunction in the ability to reduce nitrite to nitric oxide.

Conclusions: These data suggest that the potential cardioprotective effects of nitrite during exercise training may be limited by the downregulation of myoglobin.

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