In Vivo Fluorometric Assessment of Cyclosporine on Mitochondrial Function During Myocardial Ischemia and Reperfusion  Muneaki Matsubara, MD, Mahsa Ranji,

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In Vivo Fluorometric Assessment of Cyclosporine on Mitochondrial Function During Myocardial Ischemia and Reperfusion  Muneaki Matsubara, MD, Mahsa Ranji, PhD, Bradley G. Leshnower, MD, Mio Noma, MD, Sarah J. Ratcliffe, PhD, Britton Chance, PhD, Robert C. Gorman, MD, Joseph H. Gorman, MD  The Annals of Thoracic Surgery  Volume 89, Issue 5, Pages 1532-1537 (May 2010) DOI: 10.1016/j.athoracsur.2010.01.065 Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Comparison of area at risk (AR) and infarct sizes (IS) among the untreated (UnT), cyclosporine A (CsA) preinfarction (CsAp), and CsA reperfusion (CsAr) groups. Mean values are shown with the standard error of the mean (error bars). The area at risk is expressed as a percentage of the left ventricle, and the infarct size is expressed as a percentage of the area at risk. The area at risk was not significantly different between groups. Infarct size was significantly greater in the untreated group than in either of the CsA groups (*p < 0.01). Infarct size was the same in both CsA groups. The Annals of Thoracic Surgery 2010 89, 1532-1537DOI: (10.1016/j.athoracsur.2010.01.065) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Comparison of mean redox ratio (RR) between the untreated (UnT; black circle), cyclosporine A (CsA) preinfarction (CsAp; white circle) and CsA reperfusion (CsAr; black triangle) groups throughout the time course of the experiment. There were no significant differences among the groups during the baseline or infusion phases. During ischemia, the CsAp curve is significantly different from the UnT and CsAr groups. During reperfusion, all three curves were significantly different. The average rate of increase of the redox ratio during the first 70 minutes of reperfusion, as assessed by a best-fit line through all the data points, was significantly greater in the UnT and CsAr groups than it was in the CsAp group (0.005 min−1 vs 0.003 min−1; p < 0.001). After 90 minutes of reperfusion, the CsAr curve began to deviate from the UnT curve. Error bars represent standard error of the mean. The Annals of Thoracic Surgery 2010 89, 1532-1537DOI: (10.1016/j.athoracsur.2010.01.065) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Representative transmission electron photomicrographs of rabbit myocardium images (original magnification ×30,000) compare the differences among the mitochondria of the (A) normal, (B) untreated, (C) cyclosporine A (CsA) preinfarction, and (D) CsA reperfusion groups. The mitochondria of the normal myocardium are tightly packed and possess an intact mitochondrial membrane and well-organized cristae, unlike the untreated group, that is characterized by swollen, loosely packed, vacuolated, and completely disrupted mitochondria. Although the CsA preinfarction and reperfusion groups demonstrate mitochondria with dilated cristae, their general morphology is much closer to normal than was the untreated group. The Annals of Thoracic Surgery 2010 89, 1532-1537DOI: (10.1016/j.athoracsur.2010.01.065) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions