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Structural and functional assessment of an experimental model of takotsubo cardiomyopathy (648.8)
Author(s) -
Sachdeva Jaspreet,
Dai Wangde,
Kloner Robert
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.648.8
Subject(s) - edema , medicine , cardiomyopathy , cardiology , infiltration (hvac) , necrosis , lipid droplet , histology , endocrinology , pathology , heart failure , physics , thermodynamics
Objective: The purpose of our study was to assess the characteristics and time course of functional and histological abnormalities in an experimental model of Takotsubo Cardiomyopathy (TC). Methods: Male Sprague‐Dawley rats were injected subcutaneously with either a single or two doses (at 24hrs interval) of isoproterenol (ISO; 25‐300 mg/kg). Echocardiographic and morphological changes were assessed either 24hrs or 7days after the last ISO dose. Results: On day 2‐3 rats demonstrated apical akinesis蠅10% of the LV circumference (n=13), apical akinesis<10% (n=17) or no‐akinesis (n=10); the basal function was preserved. The apical fractional shortening (FS) on day 2‐3 was reduced at 16±3% (p<0.05) in the Akinesis蠅10% subgroup compared to sham‐controls at 47±4%. Apical wall motion abnormality completely resolved on day 8. Histology on day 2‐3 revealed sub‐endocardial necrosis, monocyte infiltration, interstitial edema, vacuoles and lipid droplets. Semiquantitative scoring showed a significant increase in necrotic lesions to 2.8±0.3 in the akinesis蠅10%, 2.1±0.2 in the akinesis<10% and 2±0 in the no‐akinesis subgroups vs 0.4±0.1 in the sham‐controls (p<0.05) on day 2‐3. On day 8, extensive fibrosis along with necrotic lesions was present. Ultrastructural analysis on day 2‐3 showed disrupted myofibrils, abundant lipid droplets, interstitial edema and mitochondria with dissolved cristae, calcium phosphate deposits and dense bodies. Conclusion: TC can be mimicked in a rat model of ISO exposure that demonstrates apical ballooning on days 2‐3 with full recovery of systolic regional wall motion abnormality despite the presence of persistent foci of necrosis and fibrosis on day 8.