1. Therapeutic Effect of Midkine on Cardiac Remodeling in Infarcted Rat Hearts 
Shinya Fukui, MD, Satoru Kitagawa-Sakakida, MD, PhD, Sin Kawamata, MD, PhD, Goro Matsumiya, MD, PhD, Naomasa Kawaguchi, PhD, Nariaki Matsuura, MD, PhD, Yoshiki Sawa, MD, PhD 
The Annals of Thoracic Surgery 
Volume 85, Issue 2, Pages (February 2008)
DOI: /j.athoracsur
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

2. Fig 1
(A) Expression of midkine (MDK) mRNA in infarcted rat hearts. Open symbols represent the infarcted left ventricular myocardium, and closed symbols represent the noninfarcted myocardium of ligated left anterior descending artery (LAD) Lewis hearts. (B) Immunohistochemical staining for MDK protein showed MDK in the surviving cardiomyocytes of the border zone and infarcted area (arrowhead) but not in the noninfarcted area of the heart after myocardial infarction. Left, border-zone area in the hematoxylin-eosin–stained heart; middle, border-zone area in the anti-MDK–stained heart; right, noninfarcted area in the anti-MDK-stained heart.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

3. Fig 2
Echocardiographic assessments of cardiac function after midkine (MDK) treatment. Changes in left ventricular (LV) end-diastolic area (A), LV end-systolic area (B), or ejection fraction (C) from baseline measurements for the groups treated with gel alone (open symbols) or with 25 μg recombinant MDK (closed symbols). Repeated measurement analysis of variance indicated that the two curves were significantly different (A, p < 0.01; B, p < 0.05; C, p < 0.01), and the comparisons at each time point also indicated significant differences (*p < 0.05; **p < 0.01 versus control [Cont.]). This attenuation of LV remodeling was dose dependent, as judged from the change in LV end-diastolic area 6 weeks after treatment (D) (*p < 0.05 versus control).
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

4. Fig 3
Morphometric analysis of infarcted rat hearts after midkine (MDK) treatment. Hearts treated with gel alone or with 25 μg MDK were stained with Masson’s trichrome, and two representative sections from each group are shown. (A) Left, gel-alone treated control; right, MDK treated. Note the smaller left ventricle cavity and thicker infarct scar and left ventricular muscle in the MDK-treated hearts. (B, C) The thickness and the length of the myocardial infarction (MI) area were thicker and shorter in the MDK-treated hearts. (D) The infarct scar area was not significantly affected by any dose of MDK injected. (E) The area of the noninfarcted muscle was dose-dependently increased by the injection of MDK. (Each group, n = 10.) (EF = ejection fraction; LVEDA = left ventricular end-diastolic area; W = weeks.)
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

5. Fig 4
Assessment of the collagen volume fraction (CVF) in the gel-treated control and midkine (MDK)-treated hearts. Sections of heart were stained with picro-sirius red staining. Infarcted area in the MDK-treated hearts showed striking accumulation of collagen (A, upper left: gel-alone treated control; upper right: MDK-treated in the infarcted area). The gel-treated control hearts revealed homogeneous collagen volume fraction in their noninfarcted myocardium (A, lower left: gel-treated control; lower middle: MDK-treated in the noninfarcted area; lower right: age-matched normal rat hearts). (B) Left, the collagen volume fraction in the infarcted area was significantly greater in the MDK-treated hearts than in the gel-treated control hearts. Right, the collagen volume fraction in the MDK-treated hearts was significantly less in the noninfarcted area. (MI = myocardial infarction.)
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

6. Fig 5
Assessment of vascular density in the gel-treated control and midkine (MDK)-treated hearts. (A) Sections of heart were stained with an antibody to von Willebrand factor, and most of the positive vessels were observed in the infarct scar area or the border zone of the MDK-treated hearts (upper: low magnification; lower: high magnification). (B) The vascular density in the MDK-treated hearts was more than twice that in the gel-treated control hearts. Arrowheads indicate von Willebrand factor-positive vessels.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

7. Fig 6
Assessment of cardiac myocyte remodeling in the gel-treated control and midkine (MDK)-treated hearts. (A) Hearts treated with gel alone or 25 μg MDK were periodic acid-Schiff stained. Age-matched normal Lewis hearts were stained for comparison. The cardiomyocyte width (B), length (C), and cell size (D) were measured. The cardiomyocytes of the MDK-treated hearts were significantly less hypertrophic than those of the gel-treated control hearts, although the cells were still significantly hypertrophic compared with the normal cardiomyocytes.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions