Nathalie Roy, MD, Ingeborg Friehs, MD, Douglas B

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Dopamine Induces Postischemic Cardiomyocyte Apoptosis In Vivo: An Effect Ameliorated by Propofol Nathalie Roy, MD, Ingeborg Friehs, MD, Douglas B. Cowan, PhD, David Zurakowski, PhD, Francis X. McGowan, MD, Pedro J. del Nido, MD The Annals of Thoracic Surgery Volume 82, Issue 6, Pages 2192-2199 (December 2006) DOI: 10.1016/j.athoracsur.2006.06.086 Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Left ventricular (LV) diastolic pressure recorded from 60 to 360 minutes of reperfusion in vivo in postischemic hearts reperfused without drugs (IR [diamonds]), with dopamine (IR+D [squares]), and with dopamine and propofol (IR+D+P [triangles]). Data are mean ± SE. (*p < 0.01 versus IR and p < 0.05 versus IR+D.) The Annals of Thoracic Surgery 2006 82, 2192-2199DOI: (10.1016/j.athoracsur.2006.06.086) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 (A–F) Representative photomicrographs depicting terminal nick-end labeling (TUNEL) stained (green), DAPI (blue), and desmin stained (red) left ventricular tissue section from (A) control and (B–F) postischemic hearts reperfused in vivo for 6 hours. (Bar scale = 50 microns.) Hearts were exposed to (B) no drugs at reperfusion (IR), (C) dopamine 20 μg · kg−1 · min−1 (IR+D, (D) dopamine 20 μg · kg−1 · min−1 plus propofol 500 to 600 μg · kg−1 · min−1 (IR+D+P), (E) propofol 500 to 600 μg · kg−1 · min−1 (IR+ P), (F) and dopamine 20 μg · kg−1 · min−1 plus lipid emulsion (IR+D+L). (G) Quantitative data are summarized, with the number of TUNEL-positive nuclei expressed as apoptotic nuclei (AN) per 1,000 nuclei. Data are mean ± SE. (*p < 0.01 versus IR+D and p < 0.05 versus IR, IR+D+P, IR+P, and IR+D+L. #p = 0.01 versus IR and IR+D+P. $p < 0.05 versus IR and IR+D+P.) The Annals of Thoracic Surgery 2006 82, 2192-2199DOI: (10.1016/j.athoracsur.2006.06.086) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 (A) Representative DNA laddering on 1% Agarose gel in hearts from control (C) and postischemic hearts reperfused for 6 hours in vivo with no drugs (IR), dopamine (IR+D), dopamine plus propofol (IR+D+P), and propofol only (IR+P). (B) Graph representing the percentage of hearts where positive DNA laddering was observed. The Annals of Thoracic Surgery 2006 82, 2192-2199DOI: (10.1016/j.athoracsur.2006.06.086) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 (A) Representative Western immunoblot (total protein extract) for pro–caspase-3 (32KDa) and the active caspase-3 fragment (17KDa) in control and postischemic hearts reperfused with no drugs (IR), dopamine (IR+D), dopamine plus propofol (IR+D+P), and propofol only (IR+P). (B) Ratio of apoptosis-related cleaved caspase-3 protein/pro–caspase-3 in control and postischemic hearts (laser densitometry data in arbitrary densitometry units [ADU]). (*p < 0.05 IR+D and IR+P versus C, IR, and IR+D+P; n = 4 in each group). The Annals of Thoracic Surgery 2006 82, 2192-2199DOI: (10.1016/j.athoracsur.2006.06.086) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions