Heart function as measured by ECHO and invasive left heart catheterization for FXN KO and controls at ages 30, 45 and 65 days.

<p>Heart function as measured by ECHO and invasive left heart catheterization for FXN KO and controls at ages 30, 45 and 65 days.</p

Abnormal cardiac mitochondria ultrastructure is accompanied by respiratory inhibition in FXN KO hearts.

<p>(a) Representative images from electron micrographs of cardiomyocytes viewed at 11,000x. Mitochondrial ultrastructure abnormalities were apparent in FXN KO sections and progressed from days 30 to 65. Findings included matrix density loss, mitochondrial-to-sarcomere disarrangement, and accumulation and clumping of mitochondria. FXN KO day 65 mitochondria demonstrate cristae collapse and dissolution, and hyperdense inclusions. Arrowhead = collapsed cristae; arrow = electron-dense intramitochondrial inclusions. (b) Myofibril:mitochondria area ratios were significantly decreased at day 65 in FXN KO compared to controls (n = 3–8 micrographs per strain at each age). (c) Mitochondrial functional assays demonstrated significantly decreased respiratory control ratios in FXN KO compared to controls. There were 2–4 assay runs on pooled mitochondria from FXN KO (n = 8–12 hearts), or pooled mitochondria from controls (n = 4–6 hearts), with 2–3 pooled hearts per run.</p

FXN KO hearts exhibit features of maladaptive ventricular remodeling.

<p>(a) Cardiac fibrosis is progressive in the FXN KO heart. Ventricular tissue was stained using Masson’s Trichrome to detect blue-staining fibrous tissue. (b) Percent area collagen was significantly increased in FXN KO hearts at postnatal day 65 compared to controls. (c) Evidence of cardiomyocyte degeneration in the FXN KO at day 65 is demonstrated by vacuolation on H&E staining.</p