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Autonomic neuropathy in streptozotocin diabetic rats: effect of acetyl-L-carnitine
Authors:Lo Giudice Pietro  Careddu Antonia  Magni Giuseppina  Quagliata Teresa  Pacifici Licia  Carminati Paolo
Institution:Department of Pharmacology, Research and Development, Sigma Tau, Pomezia 00040, Italy. guidicepietro.lo@sigma-tau.it
Abstract:The present study was designed to characterize cardiac autonomic neuropathy in streptozotocin-induced (45 mg/kg i.v.) diabetic rat by analysis of heart rate variability (HRV), and to assess, in this model, the effects of treatment with acetyl-L-carnitine (ALC). Heart rate was reduced in diabetic rats (332+/-22 vs. 411+/-35 beat per min; P<0.0001). This bradycardia was partly reversed with ALC (369+/-52 beat per min; P<0.05 vs. untreated). Both time- and frequency-domain parameters of HRV were significantly reduced in diabetic rats. The reduction of spectral power was around 50% at high frequencies and about 70% at low frequencies, suggesting a decrease of parasympathetic activity. Low/high frequency ratio was significantly decreased in diabetic rats suggesting decreased sympathetic tone, while nonlinear analysis indicated a reduction of the chaotic complexity of heart rate dynamics in diabetic rats. Standard deviation of heart rate in ALC-treated rats was significantly higher than in untreated diabetic rats (P<0.0001). ALC counteracts the reduction of the power spectrum observed in diabetic animals (P<0.0005) normalizing the spectra profile. ALC restored chaotic complexity of heart rate dynamics. These results on the whole indicate that both sympathetic and parasympathetic cardiac tone were reduced significantly in diabetic rats and that ALC treatment prevents the development of autonomic neuropathy in streptozotocin-induced diabetes in rats.
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