1. Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility
- Author
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Arthur W. Wallace, Kimberly A. Spaulding, Mark B. Ratcliffe, David H. Lovett, Liang Ge, Farshid Faraji, Anthony J. Baker, Kiyoaki Takaba, David Saloner, Guanying Wang, Esteban Aguayo, Alexander Collins, and Bader, Michael
- Subjects
0301 basic medicine ,Myocardial Infarction ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Cardiovascular ,Biochemistry ,Diagnostic Radiology ,0302 clinical medicine ,Superoxides ,Medicine and Health Sciences ,Medicine ,Myocardial infarction ,lcsh:Science ,Energy-Producing Organelles ,Doxycycline ,Mammals ,Multidisciplinary ,medicine.diagnostic_test ,Radiology and Imaging ,Ventricular wall ,Eukaryota ,Heart ,Oxides ,Ruminants ,Magnetic Resonance Imaging ,3. Good health ,Mitochondria ,Chemistry ,Heart Disease ,Vertebrates ,Physical Sciences ,Cardiology ,Matrix Metalloproteinase 2 ,Border zone ,Anatomy ,Cellular Structures and Organelles ,Wall thickness ,medicine.drug ,Research Article ,Biotechnology ,medicine.medical_specialty ,Catheters ,General Science & Technology ,Imaging Techniques ,Bioenergetics ,Myofilaments ,Research and Analysis Methods ,Real-Time Polymerase Chain Reaction ,Contractility ,03 medical and health sciences ,Diagnostic Medicine ,Internal medicine ,Animals ,Heart Disease - Coronary Heart Disease ,Sheep ,business.industry ,Animal ,Myocardium ,lcsh:R ,Organisms ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Magnetic resonance imaging ,Cell Biology ,medicine.disease ,Myocardial Contraction ,Cytoskeletal Proteins ,Disease Models, Animal ,030104 developmental biology ,Disease Models ,Amniotes ,Cardiovascular Anatomy ,lcsh:Q ,Medical Devices and Equipment ,business ,Reactive Oxygen Species ,Large animal - 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