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Ishiguro H, Horiba M, Takenaka H, et al. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome. Front Physiol. 2011;2:27doi: 10.3389/fphys.2011.00027.
Ishiguro, H., Horiba, M., Takenaka, H., Sumida, A., Opthof, T., Ishiguro, Y. S., Kadomatsu, K., Murohara, T., & Kodama, I. (2011). A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome. Frontiers in physiology, 227. https://doi.org/10.3389/fphys.2011.00027
Ishiguro, Hisaaki, et al. "A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome." Frontiers in physiology vol. 2 (2011): 27. doi: https://doi.org/10.3389/fphys.2011.00027
Ishiguro H, Horiba M, Takenaka H, Sumida A, Opthof T, Ishiguro YS, Kadomatsu K, Murohara T, Kodama I. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome. Front Physiol. 2011 Jun 23;2:27. doi: 10.3389/fphys.2011.00027. eCollection 2011. PMID: 21738508; PMCID: PMC3125584.
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Front Physiol. 2011 Jun 23;2:27. doi: 10.3389/fphys.2011.00027. eCollection 2011.

A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome.

Frontiers in physiology

Hisaaki Ishiguro, Mitsuru Horiba, Hiroharu Takenaka, Arihiro Sumida, Tobias Opthof, Yuko S Ishiguro, Kenji Kadomatsu, Toyoaki Murohara, Itsuo Kodama

Affiliations

  1. Research Institute of Environmental Medicine, Nagoya University Nagoya, Japan.

PMID: 21738508 PMCID: PMC3125584 DOI: 10.3389/fphys.2011.00027

Abstract

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.

Keywords: acute coronary syndrome; intracoronary injection; ischemia/reperfusion injury; midkine

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