1. Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.
- Author
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Spaulding, Kimberly, Takaba, Kiyoaki, Collins, Alexander, Faraji, Farshid, Wang, Guanying, Aguayo, Esteban, Ge, Liang, Saloner, David, Wallace, Arthur W, Baker, Anthony J, Lovett, David H, and Ratcliffe, Mark B
- Subjects
Animals ,Sheep ,Myocardial Infarction ,Disease Models ,Animal ,Reactive Oxygen Species ,Doxycycline ,Magnetic Resonance Imaging ,Myocardial Contraction ,Matrix Metalloproteinase 2 ,Real-Time Polymerase Chain Reaction ,Disease Models ,Animal ,General Science & Technology - Abstract
Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p
- Published
- 2018