Key result
Coronary autologous-aggregated platelet injection reliably induces myocardial infarction with troponin peaking at ~297 μg/mL in sheep.
Why the study?
There is a paucity of a biological large animal model of myocardial infarction that closely mimics the human pathophysiology of MI.
Absolute Event Rate: 297.4% vs 0%
Provides a catheter-based ovine thrombotic MI model for preclinical testing; leaves open human translation pending further validation.
OBJECTIVE: There is a paucity of a biological large animal model of myocardial infarction (MI). We hypothesized that, using autologous-aggregated platelets, we could create an ovine model that was reproducible and more closely mimicked the pathophysiology of MI. METHODS: Mepacrine stained autologous platelets from male sheep (n = 7) were used to create a myocardial infarction via catheter injection into the mid-left anterior descending (LAD) coronary artery. Serial daily serum troponin measurements were taken and tissue harvested on post-embolization day three. Immunofluorescence microscopy was used to detect the mepacrine-stained platelet-induced thrombus, and histology performed to identify three distinct myocardial (infarct, peri-ischemic "border zone," and remote) zones. RESULTS: Serial serum troponin levels (μg/mL) measured 0.0 ± 0.0 at baseline and peaked at 297.4 ± 58.0 on post-embolization day 1, followed by 153.0 ± 38.8 on day 2 and 76.7 ± 19.8 on day 3. Staining confirmed distinct myocardial regions of inflammation and fibrosis as well as mepacrine-stained platelets as the cause of intravascular thrombosis. CONCLUSION: We report a reproducible, unique model of a biological myocardial infarction in a large animal model. This technique can be used to study acute, regional myocardial changes following a thrombotic injury.
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Spata et al. (2013) studied Myocardial Infarction (n=7). Autologous-aggregated platelets vs. Baseline (pre-embolization) was evaluated on Peak serum troponin level (μg/mL) on post-embolization day 1. Injection of autologous-aggregated platelets into the mid-LAD coronary artery successfully created a reproducible myocardial infarction in an ovine model, with peak troponin levels reaching 297.4 μg/mL on day 1.
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