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 ...

A variety of contractility defects have been reported in the streptozotocin (STZ)-induced diabetic rat heart including alterations to the amplitude and time course of cardiac muscle contraction. 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. Electrocardiogram (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 ). Heart rate (HR), physical activity and body temperature declined rapidly 3-5 days after administration of STZ. The effects became more conspicuous with time and reached a new steady state approximately 10 days after STZ treatment when HR was 255 ± 8 beats min −1 in diabetic rats compared to 348 ± 17 beats min −1 in age-matched controls. Heart rate variability (HRV) was also significantly reduced after STZ treatment (18 ± 3 beats min −1 ) compared to controls (36 ± 3 beats min −1 ). Reduced physical activity and/or body temperature may partly underlie the reduction in HR and HRV. Reductions in power spectral density at higher frequencies (2.5-3.5 Hz) suggest that parasympathetic drive to the heart may be altered during the early stages of STZ-induced diabetes. Short-term diabetes-induced changes in vital signs can be effectively tracked by continuous recording using a telemetry system.

In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data were acquired for 2 weeks each month. Non-fasting blood glucose, glucose tolerance and body weight were measured periodically. In GK rats, growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased compared with age-matched Wistar control animals. Heart rate was significantly lower in GK compared with control rats at 2, 7 and 15 months of age. At 2 months of age, HR was 316 ± 6 beats min −1 in GK rats compared with 370 ± 7 beats min −1in Wistar control animals. There was a progressive age-dependent decline in HRV in Wistar control rats; however, HRV in GK rats did not alter significantly with age. Heart rate variability was significantly reduced in GK compared with Wistar control rats at 2 and 7 months. At 2 months of age, HRV was 28 ± 2 beats min −1 in GK rats compared with 38 ± 3 beats min −1 in Wistar control rats. Reduced HR in GK rats may be an inherited characteristic. The absence of agedependent reductions in HRV in GK rats may be a consequence of an underlying impairment of autonomic control which manifests at early age.

1. Streptozotocin (STZ)-induced diabetic cardiomyopathy is frequently associated with depressed diastolic/systolic function and altered heart rhythm. 2. The effects of insulin treatment on heart rhythm, body temperature and physical activity in STZ-induced diabetic rats were investigated using biotelemetry techniques. 3. 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. Electrocardiogram, physical activity and body temperature data were recorded with a telemetry system for 10 days before STZ treatment, for 20 days following administration of STZ (60 mg/kg) and thereafter, for 30 days while rats received daily insulin. 4. Heart rate, physical activity and body temperature declined rapidly 3-5 days after administration of STZ. Pre-STZ heart rate was 362 +/- 7 b.p.m., falling to 266 +/- 12 b.p.m. 5-15 days after STZ with significant recovery to 303 +/- 14 b.p.m. 10-20 days after commencement of insulin. Pre-STZ body temperature was 37.5 +/- 0.1C, falling to 37.2 +/- 0.2C 5-15 days after STZ with significant recovery to 37.5 +/- 0.1C 10-20 days after commencement of insulin. Physical activity and heart rate variability were also reduced after STZ but there was no significant recovery during insulin replacement. 5. Defective autonomic regulation and/or mechanisms of control that are intrinsic to the heart may underlie disturbances in heart rhythm in the STZ-induced diabetic rat.

Ventricular electrical conduction has been investigated in the streptozotocin (STZ)-induced diabetic rat. Diabetes was induced with a single injection of STZ (60 mg/kg bodyweight, ip). The ECG was measured continuously, in vivo, using a biotelemetry system. Left ventricular action potentials were recorded with an extracellular suction electrode. Expression of mRNA transcripts for selected ion transport proteins was measured in left ventricle with real-time RT-PCR. At 10 weeks after STZ treatment, in vivo heart rate (HR) was reduced (267 +/- 3 vs. 329 +/- 5 BPM), QRS complex duration and QT interval were prolonged in diabetic rats compared to controls. In vitro spontaneous HR was reduced and paced heart action potential repolarization was prolonged in diabetic rats compared to controls. The mRNA expression for Kcnd2 (I (to) channel) and Kcne2 (I (kr) channel) was significantly reduced in diabetic rats compared to controls. Altered gene expression and, in particular, genes that encode K(+) channel proteins may underlie delayed propagation of electrical activity in the ventricular myocardium of STZ-induced diabetic rat.