Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model Nobuyuki Ishibashi, MD, Yusuke.

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Presentation transcript:

Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model Nobuyuki Ishibashi, MD, Yusuke Iwata, MD, Toru Okamura, MD, David Zurakowski, PhD, Hart G.W. Lidov, MD, Richard A. Jonas, MD The Journal of Thoracic and Cardiovascular Surgery Volume 140, Issue 6, Pages 1408-1415.e3 (December 2010) DOI: 10.1016/j.jtcvs.2010.03.008 Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Overall histologic damage and neurologic recovery. A, Ischemia–ULF and ischemia–CA induce the same level of histologic damage. B, Neurologic recovery measured by neurologic deficit score is significantly worse in ischemia–CA compared with ischemia–ULF. Data are shown as standard error of the mean. Two ischemia groups are compared by ANOVA with Bonferroni comparison. ∗P < .01 vs control by ANOVA with Bonferroni comparison. ULF, Ultra–low flow bypass; CA, circulatory arrest; ANOVA, analysis of variance. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1408-1415.e3DOI: (10.1016/j.jtcvs.2010.03.008) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Biomarker of severe histologic damage. A, Animals with severe injury have significantly reduced recovery of functional capillary density in the early postischemic phase. B, The number of adherent leukocytes in animals with moderate injury is decreased after CPB; on the other hand, the number in animals with severe injury is not changed. C, Reduced tissue oxygen index during the ischemic phase and early postischemic phase is a significant predictor of severe injury. D, Tissue oxygen index during rewarming is significantly associated with total histologic score. RW, Rewarming; CPB, cardiopulmonary bypass; CA/LF, circulatory arrest or ultra–low flow bypass; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 by unpaired Student t test. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1408-1415.e3DOI: (10.1016/j.jtcvs.2010.03.008) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Regional neuronal damage. A-B, Cerebral cortex; all neurons necrotic (original magnifications: A, 20×; B, 60×). C, Cerebral cortical neuronal injury is not different between 2 ischemia groups. D, Majority of caudate nucleus neurons ischemic (original magnification 20×). E, All caudate nucleus neurons ischemic (original magnification 60×). F, The caudate nucleus is vulnerable to ischemia–CA compared with ischemia–ULF. G-H, All hippocampus pyramidal cells ischemic (original magnifications: A, 20×; B, 60×). I, Hippocampus is vulnerable to ischemia–ULF compared with ischemia–CA. J-K, Majority of cerebellar Purkinje cells ischemic (original magnifications: A, 20×; B, 60×). L, Purkinje cell damage is not different between 2 ischemia groups. Data are shown as standard error of the mean. Two ischemia groups are compared by ANOVA with Bonferroni comparison. ∗P < .01 versus control by ANOVA with Bonferroni comparison. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1408-1415.e3DOI: (10.1016/j.jtcvs.2010.03.008) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Biomarkers of regional neuronal damage. A, Functional capillary density at 5 minutes after rewarming demonstrated a significant positive relationship with damage to the caudate nucleus (P < .01) by logistic regression. This was consistent with area under the receiver operating characteristic curve (area under the curve = 0.831). The curve shows a decreasing probability of damage (defined by at least 1 point on histology) with higher values after rewarming. Theoretical curve and 95% confidence intervals were determined by logistic regression modeling (n = 32). B, Postbypass number of adherent leukocytes was positively correlated with damage to parietal cortex (at least 1 point) and Purkinje cells (at least 2 points) on histology. Curves for parietal cortex (P < .05) and Purkinje cells (P < .01) were determined using logistic regression (n = 32). Receiver operating characteristic analysis revealed an excellent discrimination of leukocytes in predicting Purkinje cell damage based on area under the curve (area under the curve = 0.864). C, Lower tissue oxygen index values at 5 minutes after rewarming were found to be predictive of greater neuronal damage in each region (all P < .01). Probability of damage for each region is represented by curves derived from logistic regression analysis. Damage was defined as at least 1 point for each region, except for Purkinje cells (n = 48), where damage was defined as 2 or more points. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1408-1415.e3DOI: (10.1016/j.jtcvs.2010.03.008) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Study protocol. The pH-stat strategy was used and 30% hematocrit level was maintained in all animals during CPB. After normothermic full-flow bypass, animals underwent 40 minutes of cooling to a temperature of 25°C or 34°C according to the protocol. After cooling, circulatory arrest or ultra–low flow perfusion was initiated for 60 minutes. Animals were warmed to 37°C over 40 minutes of rewarming with a flow rate of 100 mL · kg−1 · min−1. TOI was recorded using NIRS every 10 seconds after the induction of anesthesia and for 3 hours after weaning from CPB. IVM was performed at baseline; at 10 minutes of normothermic CPB; at 20 and 40 minutes of cooling; at every 15 minutes during circulatory arrest or ultra–low flow period; 5, 15, 30, and 40 minutes of rewarming; and at 30, 60, 120, and 180 minutes after weaning from CPB. CPB, Cardiopulmonary bypass; NT, normothermia; CA/LF, circulatory arrest or ultra–low flow bypass; RW, rewarming; NIRS, near-infrared spectroscopy; IVM, intravital microscopy; NDS, neuronal deficit score; OPC, overall performance category; TOI, tissue oxygen index. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1408-1415.e3DOI: (10.1016/j.jtcvs.2010.03.008) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions