Two months old mice (n=18) received 3 6OH-DA injections (200 mg/kg, ip) or saline (n = 6) at 3 days of interval. 15 and 30 days after first injection, heart rate spectral variability (HRV, FFT) was analyzed in low frequency (LF: 0.15-1.5 Hz) and high frequency (HF: 1.5-5 Hz) ranges and LH/HF ratio was calculated. After sacrifice, blood was withdrawn for catecholamine determination (HPLC). Hearts were fixed (formaldehyde 10 % ) for histology or frozen for western blot analysis (tyrosine hydroxylase, TH).
Indicate that compared to controls (1410¡À145 pg/ml) plasma norepinephrine levels were significantly lower at D15 (766¡À186 pg/ml) and D30 (675¡À288 pg/ml) after 6OH-DA without change in epinephrine. TH expression was absent at D15 and significantly lower than in controls at D30. When compared to controls (48.5¡À6.2 % ), LF HRV was significantly reduced at D15 (31.6¡À5.4 % ) but not at D30 (58.2¡À16.2 % ) without change in HF. LF/HF ratio was lower in 6OH-DA treated mice at D15 (0.5¡À0.1 vs 1.3¡À0.2 in controls) but not at D30 (1.6¡À0.3). At D15, 6-OH-DA hearts exhibited mild structural abnormalities with wavy cardiomyocyte appearance in septum. At D30, histological abnormalities were diffuse with myocytes intersecting at various angles with bundles wavy appearance. Variability in cell size with anisocaryosis, attenuated myocytes with perinuclear halo and shaped nuclei were observed. No inflammation, interstitial fibrosis or necrosis was noticed.
This study suggests that heart denervation induces myocardial tissue disorganization. Relationship between these changes and sympathetic nerve destruction and/or catecholamine depletion remains to be elucidated. Apart from physiological significance, these results also bring new structural basis to explain increased risk of cardiac disease during autonomic failure.