Nitric oxide synthase inhibitors decrease coronary sinus-free radical concentration and ameliorate myocardial stunning in an ischemia-reperfusion model
Yi Zhang, MD, PhDa,
Jeffrey W. Bissing, DOa,
Linjing Xu, MSa,
Alan J. Ryan, PhDa,
Sean M. Martin, BAa,
Francis J. Miller, Jr, MDa,
Kevin C. Kregel, PhDa,
Garry R. Buettner, PhDa and
Richard E. Kerber, MD, FACCa
a the Cardiovascular Center, University of Iowa, Iowa City, Iowa, USA
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Figure 1 Coronary sinus concentration of ascorbate free radical (Asc·–) after ischemia-reperfusion sequences. The rise in Asc·– concentration is significantly lower in the animals receiving the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA).
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Figure 2 Fractional area shortening by echocardiography after ischemia and reperfusion. A significant decline in fractional area shortening by echocardiography occurs during ischemia in both animal groups. In animals receiving saline a further decline in fractional area shortening (FAS) is seen after reperfusion, indicating "stunning"; in the NG-nitro-L-arginine (L-NNA) animals, FAS after reperfusion returns to baseline levels—a cardioprotective effect.
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Figure 3 Representative photomicrograph of myocardium subjected to an occlusion-reperfusion sequence without receiving NG-nitro-L-arginine and stained as described (see text), but not incubated in antinitrotyrosine antibody. No nitrotyrosine is demonstrated. Compare to Figure 4.
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Figure 4 Representative photomicrograph of myocardium subjected to a coronary occlusion-reperfusion sequence and incubated with antinitrotyrosine antibody. Heavy nitrotyrosine staining of the cytoplasm (brown stain) is evident. Compare to Figure 3. This dog did not receive the nitric oxide synthase inhibitor NG-nitro-L-arginine.
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Figure 5 Representative photomicrograph of myocardium subjected to an occlusion-reperfusion sequence and incubated with antinitrotyrosine antibody. This dog received the nitricoxide synthase inhibitor NG-nitro-L-arginine during the occlusion-reperfusion sequence. Only minimal nitrotyrosine staining is present. Compare to Figure 4.
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