L-Arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibiting inositol-1,4,5-triphosphate Tomohiro Mizuno, MD, Masazumi.

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l-Arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibiting inositol-1,4,5-triphosphate Tomohiro Mizuno, MD, Masazumi Watanabe, MD, Tohru Sakamoto, MD, Makoto Sunamori, MD The Journal of Thoracic and Cardiovascular Surgery Volume 115, Issue 4, Pages 931-936 (April 1998) DOI: 10.1016/S0022-5223(98)70376-9 Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 1 Experimental protocol: A time line is given for the study as conducted in each heart. After 5 minutes of Langendorff perfusion (L-P) with normal modified Krebs-Henseleit bicarbonate buffer (KHB), baseline myocardial functions were carried out. After this, L-P with drugs buffered in KHB was established for a total of 10 minutes and then the heart was replaced for 30 minutes of normothermic global ischemia and reperfused with normal KHB for 30 minutes. Biopsy specimens for cGMP and calcium were taken at the baseline point, 30 minutes after ischemia, 10 minutes after reperfusion, and 30 minutes after reperfusion. In addition, separate hearts were perfused for 45 minutes with 50 ml KHB containing 20 μCi of [3H] myo-inositol for the measurements of inositol-1,4,5-monophosphate. In the C group no drug was used, whereas the L group had l-arginine administered for 10 minutes before ischemia. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 931-936DOI: (10.1016/S0022-5223(98)70376-9) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 2 Cyclic GMP content. cyclic GMP (cGMP) contents in the myocardium were measured by radioimmunoassay at baseline (Base), after 30 minutes of ischemia (I30), after 10 minutes reperfusion (R10), and after 30 minutes reperfusion (R30). In the L group, cGMP contents were significantly higher than the C group after ischemia and reperfusion. *p = 0.02, C group versus L group; #p = 0.01 compared with the values of baseline. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 931-936DOI: (10.1016/S0022-5223(98)70376-9) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 3 The content of inositol-1,4,5-monophosphate (IP3). IP3 significantly increased 10 minutes and 30 minutes after reperfusion in the C group. However, in the L group there was no differences between the value of baseline and after reperfusion. *p = 0.03, C group versus L group; #p = 0.01, compared with the values of baseline. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 931-936DOI: (10.1016/S0022-5223(98)70376-9) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 4 Cytosolic Ca2+ content. Cytosolic Ca2+ content significantly increased after ischemia and reperfusion in both groups. However, in the C group, the absolute values were significantly higher in the L group after reperfusion. *p = 0.01, C group versus L group; #p = 0.02, compared with the values of baseline. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 931-936DOI: (10.1016/S0022-5223(98)70376-9) Copyright © 1998 Mosby, Inc. Terms and Conditions