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Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: A pediatric.

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Presentation on theme: "Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: A pediatric."— Presentation transcript:

1 Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: A pediatric animal model  Jonathan R. Egan, MBBS, Tanya L. Butler, PhD, Andrew D. Cole, BAppSc, Avetis Aharonyan, MD, David Baines, MBBS, Neil Street, MBBS, Manchula Navaratnam, MBchB, Oliver Biecker, MEng, Carla Zazulak, BSc, Carol G. Au, BSc, Yee Mun Tan, BSc, Kathryn N. North, MD, David S. Winlaw, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 136, Issue 5, Pages e2 (November 2008) DOI: /j.jtcvs Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

2 Figure 1 Hemodynamic and biochemical variables. In A through F, lambs are grouped as undergoing cardiopulmonary bypass (CPB) without aortic crossclamping (AXC; solid line) and CPB with AXC (dashed line). A shows similar heart rates between groups, but after CPB, the CPB+AXC group have a significantly higher heart rate until the last 30-minute epoch of postoperative analysis (Mann–Whitney U test). B displays systolic blood pressure, which is significantly lower in the CPB+AXC group in the mid epochs after CPB (Mann–Whitney U test). C and D show mean blood pressure and diastolic blood pressure, respectively, being significantly lower in the CPB+AXC group throughout the postoperative period (mixed-model analysis). E demonstrates a higher lactate level in the CPB+AXC group just before the completion of CPB (Mann–Whitney U test). In F there is a corresponding decrease in venous saturation in this group, which remains throughout the postoperative period (Mann–Whitney U test). HR, Heart rate; MBP, mean blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure. ∗P < .05. Data shown are presented as means ± standard error of the mean. The Journal of Thoracic and Cardiovascular Surgery  , e2DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

3 Figure 2 Myocardial water. Proportion of heart as water in non–cardiopulmonary bypass (CPB) control animals (black column), lambs undergoing CPB without aortic crossclamping (AXC; gray column), and lambs undergoing CPB with AXC (white column). Significant myocardial edema was present in lambs undergoing CPB+AXC lambs, and a nonsignificant increase in myocardial water occurred in those undergoing CPB–AXC (Mann–Whitney U test). ∗P < .05. Data shown are presented as means ± standard error of the mean. The Journal of Thoracic and Cardiovascular Surgery  , e2DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

4 Figure 3 Myocardial aquaporin (AQP) 1 transcript expression. RNA was extracted from the myocardium of non–cardiopulmonary bypass (CPB) control animals (black column), lambs undergoing CPB without aortic crossclamping (AXC; gray column), and lambs undergoing CPB+AXC (white column). The quantitative real-time polymerase chain reaction results shown are representative of at least 3 individuals in each group and are representative of 3 independent sets of experiments. AQP1 mRNA was normalized to ribosomal 18S RNA (Mann–Whitney U test). ∗P < .05 versus non-CPB control animals and #P < .05 versus the CPB–AXC group. Data shown are presented as means ± standard error of the mean. The Journal of Thoracic and Cardiovascular Surgery  , e2DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

5 Figure 4 Myocardial aquaporin (AQP) 1 protein expression. AQP1 protein was obtained from the myocardium of non–cardiopulmonary bypass (CPB) control animals (black column), lambs undergoing CPB without aortic crossclamping (AXC; gray column), and lambs undergoing CPB+AXC (white column). It was measured by Western blotting, analyzed by means of densitometry, and normalized to the expression of cardiac actin. Representative results demonstrate no significant differences between groups (Mann–Whitney U test). ∗P < .05. Data shown are presented as means ± standard error of the mean. The Journal of Thoracic and Cardiovascular Surgery  , e2DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

6 Figure 5 Myocardial apoptosis. Representative results of non–cardiopulmonary bypass (CPB) control animals (black column), lambs undergoing CPB without aortic crossclamping (AXC; gray column), and lambs undergoing CPB+AXC (white column). A, Hematoxylin and eosin micrographs of ventricular myocardium taken at ×100 magnification. The CPB+AXC images are suggestive of more tissue edema, and there was no apparent necrosis. Micrographs of TdT-mediated dUTP nick-end labeling (TUNEL)–stained ventricular myocardium are shown at ×100 magnification. Appropriate positive and negative controls were performed (data not shown). No significant differences were seen in TUNEL staining. B, Graph of the results of active caspase 3 densitometry for the 3 groups from Western blot analysis, loading controlled with cardiac actin. The animals undergoing CPB+AXC demonstrated a significant increase active caspase 3 protein, which is suggestive of active early apoptotic pathways (Mann–Whitney U test). ∗P < .05. Data shown are presented as means ± standard error of the mean. The Journal of Thoracic and Cardiovascular Surgery  , e2DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

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