Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution Alasdair J. Watson, BMed.

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Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution Alasdair J. Watson, BMed (Hons), Ling Gao, PhD, Lin Sun, MBBS, Jireh Tsun, BSc (Med) (Hons), Andrew Jabbour, MBBS, PhD, Min Ru Qiu, MBBS, FRCPA, Paul C. Jansz, BMed, PhD, Mark Hicks, PhD, Peter S. Macdonald, MD, PhD The Journal of Heart and Lung Transplantation Volume 32, Issue 6, Pages 633-640 (June 2013) DOI: 10.1016/j.healun.2013.03.014 Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Figure 1 Experimental timeline and groups. The Journal of Heart and Lung Transplantation 2013 32, 633-640DOI: (10.1016/j.healun.2013.03.014) Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Figure 2 Myocardial functional recovery in response to increasing concentrations of erythropoietin (units/ml, denoted on x-axis) when added to Celsior cardioplegia: (A) aortic flow; (B) coronary flow; (C) cardiac output; and (D) heart rate. Data presented as mean ± SEM. *p < 0.05 vs control; #p < 0.05 vs EPO (0.3U/ml); and +p < 0.05 vs EPO (0.6U/ml). The Journal of Heart and Lung Transplantation 2013 32, 633-640DOI: (10.1016/j.healun.2013.03.014) Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Figure 3 Lactate dehydrogenase (LDH) concentration in coronary effluent after 45 minutes of reperfusion in response to increasing doses of erythropoietin (units/ml, denoted on x-axis) when added to Celsior cardioplegia. Box-and-whisker plot shows median, interquartile range and maximum and minimum values, Kruskal–Wallis test, p = 0.024. The Journal of Heart and Lung Transplantation 2013 32, 633-640DOI: (10.1016/j.healun.2013.03.014) Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Figure 4 Cardiac output recovery in response to timing of administration of 5 units/ml erythropoietin relative to ischemia. Data presented as mean ± SEM. Hearts that received no erythropoietin (CON) compared with those that received erythropoietin during baseline perfusion (PRE), as an additive to Celsior (DURING) and during reperfusion (POST). *p < 0.05 vs CON; and #p < 0.05 vs POST. The Journal of Heart and Lung Transplantation 2013 32, 633-640DOI: (10.1016/j.healun.2013.03.014) Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Figure 5 The protective effects of erythropoietin appear to be mediated via enhanced STAT3 signaling. Pre-treatment with stattic abrogated the effects of EPO 5U/ml on cardiac output recovery (A), lactate dehydrogenase concentration in coronary effluent after 45 minutes of reperfusion (B), and STAT3 phosphorylation (C). Neither EPO treatment nor stattic pre-treatment had any effect on Akt phosphorylation (D). Column graphs show mean ± SEM, *p < 0.05 vs control; #p < 0.05 vs STAT; +p < 0.05 vs WORT (A, C, D). Box-and-whisker plot shows median, interquartile range and maximum and minimum values. Kruskal–Wallis test, p = 0.036 (B). The Journal of Heart and Lung Transplantation 2013 32, 633-640DOI: (10.1016/j.healun.2013.03.014) Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Figure 6 Myocardial functional recovery after 10 hours of hypothermic ischemia in hearts arrested using Celsior supplemented with combinations of erythropoietin 5 units/ml (E), GTN 100 mg/liter (G) and zoniporide 1mmol/liter (Z). Data presented as mean ± SEM. *p < 0.05 vs Groups E, G, Z and EZ; #p < 0.05 vs all other groups. The Journal of Heart and Lung Transplantation 2013 32, 633-640DOI: (10.1016/j.healun.2013.03.014) Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions