Establishment of Pathological Criteria for Experimental Myocardial Infarction in Animal Model: Assessment of the Early Damage of the Myocardium
| Autor: | He-Shiuan Liang, 梁赫烜 |
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| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Traditionally histological criteria used to interpret necrotic cardiomyocytes on hematoxylin and eosin (H&E) stained tissue sections (designated as “method A” in this study) are: 1) nuclear pyknosis, karyorrhexis, and karyolysis; 2) sarcoplasmic fragmentation, flocculation, and/or the presence of contraction band; 3) inflammatory infiltration. However, these changes are usually unremarkable until at least 6 hours postnecrotic. In this study, myocardial necrosis were experimentally induced by various models: 1) monensin intoxication; 2) ligation of the left anterior descending (LAD) coronary artery for 30 min without reperfusion; 3) ligation of the left circumflex (LCX) branch of coronary artery for 30 min without reperfusion; and 4) application of calcium blocker combined with beta-antagonist to induce functional left heart failure. Three additional criteria (designated as “method B”) were also proposed in this study to interpret early cardiomyocyte necrosis or myocardial injuries on H&E stained tissue sections. They were: 1) wavy or condensed nucleus; 2) hypereosinophilia of sacroplasm with either swelling or atrophy in diameter; 3) perinuclear cloudy vacuolation likely results from swollen organelles such as mitochondria and/or sarcoplasmic reticulum. Immunohistochemistry (IHC) using antibodies against structural proteins, functional proteins, organelle-binding enzymatic proteins together with complement 9 were also employed. The IHC stained section were scored with a known system and compared statistically with methods A and B for their sensitivity or superiority in detecting early MI in tissue specimens. It revealed that method B was as sensitive as cardiac troponin I (cTnI) and telethonin (T-cap), which were more superior to other biomarkers used in detecting early necrotic events in cardiomyocytes. In instances T-cap was slightly superior to cTnI, the current gold standard. The staining for matrix metalloproteinase 2 (MMP2), an intracellular and extracellular proteins, revealed intriguing results and suggested early activation and early diagnostic potential of this molecule for necrotic events. Other biomarkers were either fair or insensitive (such as deposition C9) for detecting early necrosis in the models used here in this study. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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