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Morphological changes across the border zone of cat hearts subjected to regional ischaemia
G Greve1, S Rotevatn, L Stangeland
1Department of Anatomy, University of Bergen, Norway.
Insights
Myocardial infarction creates a distinct border zone with cellular changes. This border zone shows increased mitochondria and lipid droplets, alongside cell damage, even in areas with blood flow.
Area of Science:
- Cardiovascular Pathology
- Myocardial Ischemia Research
- Cellular Biology
Background:
- Myocardial infarction (MI) leads to complex cellular changes.
- Defining the precise boundaries and characteristics of the ischemic border zone is crucial for understanding tissue damage and potential salvage.
Purpose of the Study:
- To investigate the cellular and ultrastructural changes within the border zone of myocardial ischemia.
- To delineate the spatial extent and morphological features of the border zone using advanced microscopy.
Main Methods:
- Induction of myocardial ischemia by ligating the left anterior descending coronary artery (LAD) in open-chest cats.
- Collection of myocardial biopsies from normal, ischemic, and border zones identified by fluorescein injection and blood flow measurements.
- Detailed ultrastructural analysis using electron microscopy and morphometric analysis of myocytes and micrographs.
Main Results:
- An abrupt increase in sarcolemmal fragmentation, chromatin clumping, and necrosis was observed at the border line.
- The border zone exhibited increased mitochondrial volume and lipid droplet accumulation compared to the ischemic zone.
- Changes in the normal-facing border zone included moderate cytoplasmic edema and sarcolemmal fragility.
Conclusions:
- Myocardial ischemia induces a distinct border zone characterized by specific ultrastructural alterations.
- The border zone displays a gradient of cellular injury, with unique features distinct from both normal and fully ischemic myocardium.
- These findings highlight the complex cellular response to ischemia and the importance of the border zone in tissue fate.
Abstract:
The left anterior descending coronary artery (LAD) was ligated for 3 h in six open chest cats. Six biopsies for electron microscopy were collected from the normal, the ischaemic and the border zones as defined by in vivo injection of fluorescein and as verified by blood flow measurements. Across the fluorescein demarcation line, we collected 3 mm long border zone biopsies, extending 1.5 mm in both the normal and the ischaemic direction. Starting from the normal end twenty subsequent areas (165 microns apart) were studied. By examining a total number of 5280 myocytes we observed an abrupt increase in the number of cells with sarcolemmal fragmentation. This point called border line is accompanied by an abrupt increase in the number of cells with chromatin clumping or margination, and of cells which are mainly necrotic with a massive cytoplasmic oedema. Morphometric analysis of 576 micrographs indicates a border zone on both sides of the border line. The border zone is characterized by a larger fractional volume of mitochondria (extending 1.5-2.0 mm in the normal direction) and by a larger lipid droplet accumulation (extending 1.2 mm or less in the normal direction) than seen in the ischaemic zone. These changes are in the normal part of the border zone accompanied with a moderate cytoplasmic oedema and a fragile sarcolemma with focal disruptions.