2024-03-29T14:03:08Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00014867
2023-01-16T04:28:09Z
499:960:1165
A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome
Ishiguro, Hisaaki
Horiba, Mitsuru
Takenaka, Hiroharu
Sumida, Arihiro
Opthof, Tobias
Ishiguro, S. Yuko
Kadomatsu, Kenji
Murohara, Toyoaki
Kodama, Itsuo
open access
midkine
ischemia/reperfusion injury
intracoronary injection
acute coronary syndrome
Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigated the cardioprotective effect of midkine (MK) in swine subjected to ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT). Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller than in CONT. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher left ventricular (LV) fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow) compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we demonstrate that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.
名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成24年2月29日 石黒久昌氏の博士論文として提出された
Frontiers Media SA
2011-06
eng
doctoral thesis
http://hdl.handle.net/2237/16801
https://nagoya.repo.nii.ac.jp/records/14867
https://doi.org/10.3389/fphys.2011.00027
1664-042X
Frontiers in Physiology
2
27
乙第6962号
博士(医学)
2011-06-01
13901
名古屋大学
Nagoya University
https://nagoya.repo.nii.ac.jp/record/14867/files/o6962.pdf
application/pdf
1.1 MB
2018-02-20