Long‐term effects of streptozotocin‐induced diabetes on the electrocardiogram, physical activity and body temperature in rats

Abstract

In vivo biotelemetry studies have demonstrated that short-term streptozotocin (STZ)-induced diabetes is associated with a reduction in heart rate (HR) and heart rate variability (HRV) and prolongation of QT and QRS intervals. This study investigates the long-term effects of STZ-induced diabetes on the electrocardiogram (ECG), physical activity and body temperature. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. ECG, physical activity and body temperature data were continuously recorded with a telemetry system before and following the administration of STZ (60 mg kg −1 ) for a period of 22 weeks. HR, physical activity and body temperature declined rapidly 3-5 days after the administration of STZ. The effects became conspicuous with time reaching a new steady state approximately 1-2 weeks after STZ treatment. HR at 4 weeks was 268 ± 5 beats min −1 in diabetic rats compared to 347 ± 12 beats min −1 in age-matched controls. HRV at 4 weeks was also significantly reduced after STZ treatment (18 ± 3 beats min −1 ) compared to controls (33 ± 3 beats min −1 ). HR and HRV were not additionally altered in either diabetic rats (266 ± 5 and 20 ± 4 beats min −1 ) or age-matched controls (316 ± 6 and 25 ± 4 beats min −1 ) at 22 weeks. Reduced physical activity and/or body temperature may partly underlie the reductions in HR and HRV. In addition, the increased power spectral low frequency/high frequency ratio from 4 weeks after STZ treatment may indicate an accompanying disturbance in sympathovagal balance. Treatment of young adult rats with streptozotocin (STZ) produces a diabetic state that is characterized by loss of weight, polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinaemia and hyperglycaemia (Hakim et al. 1997). The pathophysiology of STZ-induced diabetes includes a cardiomyopathy that is frequently associated with contractile dysfunction and heart rhythm disturbances. Contractile dysfunctions, including reduced amplitude of contraction and prolonged time course of contraction and relaxation, have been frequently reported in myocytes from STZ-treated rats (Okayama et al. 1994;Yu et al. 1994;Ren & Davidoff, 1997;Howarth et al. 2001;Choi et al. 2002). Defective Ca 2+ signalling mechanisms, including reductions in L-type Ca 2+ channel current, depressed sarcoplasmic reticulum Ca 2+ uptake and release mechanisms, and reduced rate of Ca 2+ efflux on the Na + -Ca 2+ exchange, partly underlie these contractile defects (Lagadic-Gossmann et al. 1996;Chattou et al. 1999;Choi et al. 2002). Reductions in heart rate (HR) in isolated perfused heart (Li et al. 1989;Nicholl et al. 1991;Imai et al. 1991;Ravingerova et al. 1996;De Angelis et al. 2000;Nemeth et al. 2001) and spontaneous beating rate in right atria (Goyal & McNeill, 1985;Ramanadham & Tenner, 1986;Kofo-Abayomi & Lucas, 1988;Nagamine et al. 1989;Booth & Hodgson, 1993;Hicks et al. 1997;Sellers & Chess-Williams, 2000) from ...

Susceptibility of Diabetic Heart to Catecholamine-induced Arrhythmias is Independent of Contractile Dysfunction

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