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This Article Abstract Full Text (PDF) All Versions of this Article: 90/2/237    most recent expphysiol.2004.029439v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Howarth, F. C Articles by Adeghate, E Search for Related Content PubMed PubMed Citation Articles by Howarth, F. C Articles by Adeghate, E Related Collections Heart/Cardiac Muscle

Departments of ¹ Physiology³ Pharmacology⁴ Anatomy, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates² College Requirements Unit, Faculty of Engineering, United Arab Emirates University, Al Ain, United Arab Emirates

	Abstract

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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.

(Received 27 October 2004; accepted after revision 14 December 2004; first published online 7 January 2005)
Corresponding author F. C. Howarth: Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. Email: chris.howarth{at}uaeu.ac.ae

	Introduction

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Impairment of contractile force generation, abnormal filling and delayed relaxation of cardiac muscle are defects that have been reported in diabetic patients and are features that are also observed in the experimental setting (Dhalla et al. 1985; Ren & Davidoff, 1997; Choi et al. 2002). Altered amplitude of contraction and prolonged time course of contraction and relaxation have been frequently reported in myocytes from STZ-treated rat (Yu et al. 1994; Okayama et al. 1994; Ren & Davidoff, 1997; Howarth et al. 2001; Choi et al. 2002) Defects in Ca²⁺ transport including L-type Ca²⁺ channels, Na⁺–Ca²⁺ exchanger and sarcoplasmic reticulum Ca²⁺ uptake and release mechanisms may partly underlie contractile defects in the STZ-treated rat (Lagadic-Gossmann et al. 1996; Ishikawa et al. 1999; Chattou et al. 1999; Choi et al. 2002). Rhythmicity of the heart is also altered in the STZ-treated rat. Reductions in HR after weeks or months of STZ treatment have been demonstrated in vivo and in various isolated heart preparations (Kofo-Abayomi & Lucas, 1988; Li et al. 1989; Hicks et al. 1998; De Angelis et al. 2000; Nemeth et al. 2001; Lo et al. 2002). Reports on the continuous recording of vital signs such as HR, physical activity and body temperature in experimental diabetes are few. In this study a telemetry system was employed to investigate the effects of short-term STZ-induced diabetes on the ECG and in particular on HR, HRV and QRS and QT intervals on a continuous basis. The relationship between changes in HR, physical activity and body temperature in diabetic rats was also investigated for comparison.

	Methods

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Telemetry system

Heart biopotential, physical activity and body temperature were monitored using a telemetry system (Data Sciences Int., St. Paul, MN, USA). The system comprised the transmitter devices (TA11CTA-F40, Data Sciences Int.), the receivers (RPC-1), a data exchange matrix (20CH) and a PC for system configuration, control, acquisition and storage. The transmitter devices were surgically implanted in 13 young adult male Wistar rats (250–260 g) under general anaesthesia (sodium pentobarbitone, 45 mg kg^–1, I.P.). The devices were inserted into the peritoneal cavity and electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration (right foreleg and left hindleg). Animals were allowed to recover from surgery and the effects of anaesthetics for a period of 1 week when the transmitters in the animals were activated by use of a magnet switch. Data recording was started 10 days before the induction of diabetes. Ethical approval for the project was obtained from the Faculty of Medicine & Health Sciences Ethics Committee for Animal Research.

Induction of diabetes

After 10 days of telemetry data collection, diabetes was induced in seven of the 13 rats by a single intraperitoneal injection of STZ (60 mg (kg body weight)^–1; Sigma). The STZ was dissolved in a citrate-buffered solution (0.1 mol l^–1 citric acid, 0.1 mol l^–1 sodium citrate; pH 4.5). Six age-matched controls received an equivalent volume of the citrate-buffered solution alone. Body weight was measured 1 day before and 30 days after STZ treatment. Blood glucose concentration was measured 3 days and 30 days after STZ treatment.

Data collection and analysis

ECG, physical activity and body temperature data were collected for 5 min per hour per animal, 24 h per day, and 7 days per week for the duration of the study. Data recording commenced 10 days before the administration of STZ (pretreatment period) and continued until 20 days after STZ administration. From the collected ECG data, secondary physiological measurements were determined including the average 5-min HR and HRV. Unless otherwise stated, statistical comparisons were made using two-factor, analysis of variance (ANOVA). P values less than 0.01 were considered significant.

	Results

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General characteristics of the STZ-treated rat

The general characteristics of STZ-treated rats included reduced body weight gain and elevated blood glucose levels compared to age-matched controls. At 3 days after STZ treatment blood glucose concentration in diabetic rats was 265 ± 24 mg dl^–1 compared to 70 ± 4 mg dl^–1 in controls and at 30 days blood glucose concentration in diabetic rats was 309 ± 34 mg dl^–1 (n = 7) compared to 77 ± 3 mg dl^–1 (n = 6) in controls. Body weight in diabetic rats declined from 271 ± 5 g before the administration of STZ to 238 ± 14 g (n = 7) at 30 days after STZ treatment, whereas the body weight of control rats increased significantly (P < 0.01) from 247 ± 6 g to 314 ± 13 g (n = 6).

Heart rate

The HR was determined from the 5-min average of all R–R intervals in the ECG. The effects of STZ treatment on HR are shown in Fig. 1. The HR during the pretreatment period was 338 ± 9 beats min^–1 (n = 13). HR fell rapidly after the administration of STZ. At 10 days after the induction of diabetes, HR was 255 ± 8 beats min^–1 (n = 7) in STZ-treated rats compared to 348 ± 17 beats min^–1 (n = 6) in age-matched controls (Fig. 1B). The change in minimum 24-h HR at minimum physical activity after STZ treatment compared to controls are shown in Fig. 1C. At minimum levels of physical activity minimum HR was markedly reduced after STZ treatment (Fig. 1C). The effects of short-term STZ treatment on various cardiac cycle intervals are shown in Fig. 2. The intervals were calculated by first detecting the ECG characteristic points of all normal cardiac cycles, as shown in Fig. 2A. The PQ interval was defined as the time from the peak of the P wave to the Q point, the QRS interval as the time from the Q point to the S point of the QRS complex and the QT interval as the time from the Q point to the end of the T wave. The QRS and QT intervals were significantly (P < 0.05) prolonged in STZ-treated rats compared to controls (Fig. 2B–D).

View larger version (52K): [in this window] [in a new window]   Figure 1.  Effects of STZ treatment (Day 0) on HR A, mean recordings of HR in control (n = 6) and STZ-treated (n = 7) rats. B, graph showing mean HR at pretreatment (Day –5) and at Day 10 after STZ treatment. C, graph showing mean minimum HR at minimum 24-h activity after STZ treatment. Data are mean ± S.E.M., n = 6–7. **P < 0.001.

View larger version (25K): [in this window] [in a new window]   Figure 2.  Effects of STZ treatment (Day 0) on the cardiac cycle A, typical ECG record showing points at which intervals were measured. B and C, show the effects of STZ treatment on QT and QRS intervals, respectively. D, summarizes effects of STZ treatment on QT, QRS and PQ intervals. Values shown in the table are changes in interval times in comparison to the animal's pretreatment values. Data are mean ± S.E.M., n = 6–7. **P < 0.001, *P < 0.01.

The HRV was computed as the standard deviation (S.D.) of the average of normal-to-normal beats (SDANN). Specifically, the SDANN was computed by first determining the 5-minute, average HR for each animal every hour. Then, the S.D. of 12 previous HR averages and 12 subsequent HR averages was computed in order to determine the 24-h HRV. Figure 3 shows the effects of STZ treatment on the HRV. The average HRV during the pretreatment period was 26 ± 2 beats min^–1 (n = 13). Small changes in HRV were observed soon after the administration of STZ and became more conspicuous on day 5. At 10 days after STZ treatment, HRV was significantly (P < 0.01) reduced in diabetic rats (18 ± 3 beats min^–1; n = 7) compared to controls (36 ± 3 beats min^–1; n = 6).

View larger version (29K): [in this window] [in a new window]   Figure 3.  Effects of STZ treatment (Day 0) on HRV A, mean recordings of HRV in STZ-treated and control rats. B, graph showing mean HRV at pretreatment (Day –5) and at Day 10 after STZ treatment. Data are mean ± S.E.M. (n = 6–7). **P < 0.001.

To further characterize the effects of STZ-induced diabetes on autonomic neural control of HR, the 24-h power spectral density (PSD) of the HRV was computed as the average PSD of each short-term, 5-min HRV (Fig. 4D). Specifically, the short-term HRV was computed from the 5-min ECG strips by first determining the R–R interval times. Then, the intervals were analysed in order to remove outlying values due to missed beats and preventricular contractions which cause disruptions to the cardiac rhythm. The resulting intervals were subsequently interpolated to a 10-Hz sampling frequency and the average HR was subtracted in order to highlight the HR variations in the 5-min strip. Next, the PSD was computed using a Burg, 20th-order, auto-regressive estimate. Finally, 24 of the 5-min PSD estimates were averaged in order to estimate the 24-h PSD of the HRV, as shown in Fig. 4A and B. The HRV PSD was slightly increased at low frequencies (LF, 0.5–1.5 Hz) and decreased at high frequencies (HF, 2.5–3.5 Hz) in diabetic rats at 10 days after STZ treatment compared to control rats (Fig. 4B). The low frequency/high frequency (LF/HF) ratio at 10 days after STZ treatment was significantly increased in diabetic rats compared to controls (Fig. 4C).

View larger version (26K): [in this window] [in a new window]   Figure 4.  Effects of STZ treatment (Day 0) on HRV power spectral density A, shows the 24-h PSD estimate of the animals on Day –5 of the pretreatment data. B, shows the 24-h PSD of animals on day 10 after administration of STZ. C, shows the ratio of LF power to HF power bands. D, shows the algorithm to estimate the 24-h PSD. Data are mean ± S.E.M. (n = 6–7). **P < 0.001.

Physical activity was assessed by measuring changes in the animal's transmitter signal strength. Specifically, the transmitter signal strength was sampled at 64 Hz and calibrated in counts min^–1. When the animal changes its position, the corresponding transmitter signal strength is changed, which results in an increase in counts min^–1. Low counts indicate reduced physical activity in the animal. Figure 5 shows the effects of STZ treatment on physical activity. Average activity during the pretreatment period was 0.96 ± 0.14 counts min^–1 (n = 13). At 10 days after STZ treatment physical activity was significantly (P < 0.01) reduced in diabetic rats (0.33 ± 0.07 counts min^–1; n = 7) compared to controls (1.32 ± 0.29 counts min^–1; n = 6).

View larger version (32K): [in this window] [in a new window]   Figure 5.  Effects of STZ treatment (Day 0) on physical activity A, mean recordings of activity in six control and seven STZ-treated rats. B, graph showing mean activity at pretreatment (Day –5) and at Day 10 after STZ treatment. Data are mean ± S.E.M. (n = 6–7). **P < 0.001.

In addition to ECG and physical activity, the implant transmits the animal body temperature. As for HR, the temperature is measured and recorded each hour. In order to display the effects of STZ treatment on the 24-h average body temperature was computed. Figure 6 shows the effects of STZ treatment on body temperature. During the pretreatment period, the temperature was 37.5 ± 0.1°C (n = 13). At 10 days, temperature was significantly reduced in STZ-treated rats (37.1 ± 0.1°C; n = 7) compared to controls (37.5 ± 0.1°C; n = 6).

View larger version (42K): [in this window] [in a new window]   Figure 6.  Effects of STZ treatment (Day 0) on body temperature A, mean recordings of body temperature in six control and seven STZ-treated rats. B, graph showing mean body temperature at pretreatment (Day –5) and at Day 10 after STZ treatment. Data are mean ± S.E.M. (n = 6–7). *P < 0.01.

	Discussion

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Heart rate declined rapidly in diabetic rats and appeared to reach a new steady state approximately 10 days after the administration of STZ. At 10 days after the onset of diabetes, HR was reduced from 348 ± 17 beats min^–1 in controls to 255 ± 8 beats min^–1 in diabetic rats. The mechanisms underlying reduced HR in diabetic rats may include altered sympathovagal modulation of HR or defects in sinoatrial (SA) node function. Several studies have demonstrated reductions of HR in various isolated heart preparations from STZ-treated rat and the magnitude of the chronotropic effects appears to be dependent on treatment time (Kofo-Abayomi & Lucas, 1988; Li et al. 1989; Hicks et al. 1997; De Angelis et al. 2000; Nemeth et al. 2001). A reduction in basal spontaneous rate has been reported in superfused right atrial preparations at 12 weeks after STZ treatment which may suggest a specific impairment of SA node function (Kofo-Abayomi & Lucas, 1988; Hicks et al. 1997). Previous in vivo and in vitro experiments have demonstrated that reductions in HR seen in STZ-induced diabetic rats compared to controls are reversed by insulin treatment suggesting that it is the diabetes rather than STZ treatment that is responsible for the bradycardia (Li et al. 1989; Hicks et al. 1998; Zhang et al. 2002). The QT interval, which represents the time necessary to complete excitation and recovery of the ventricles, was prolonged after STZ treatment. Prolonged QT interval may be attributed to a prolongation of the action potential duration which has been reported to occur within 4–6 days after the administration of STZ (Shimoni et al. 1994). Prolongation of the action potential may be partly attributed to altered L-type Ca²⁺ current or Ca²⁺-independent transient outward K⁺ current (Shimoni et al. 1994, 1998; Chattou et al. 1999; Choi et al. 2002).

The HRV, an index of sympathovagal modulation of heart function (Ferrari et al. 1987; Bootsma et al. 1994; Aubert et al. 1999) declined rapidly after STZ treatment. At 10 days after the onset of diabetes, HRV was 18 ± 3 beats min^–1 in STZ-treated rats compared to 36 ± 3 beats min^–1 in controls. Reduced HRV after STZ treatment (Fazan et al. 1997; Lo et al. 2002) may be indicative of defective autonomic regulation of heart function. Power spectral analysis, showed a small increase in power at LF, but at HF there was a large reduction in power in diabetic rats compared to controls. The LF/HF ratio has been used as a means to assess the sympathovagal balance (Chiou & Zipes, 1998) and in the current experiments the LF/HF ratio was significantly reduced 10 days after the onset of diabetes. The boundaries for HF and LF are not clearly defined in the literature. Ishii et al. (1996) set the LF and HF bands at 0.1–1.0 Hz and 1.0–5.0 Hz, respectively, for studies in mice and voles. In rat, the boundaries have been set for LF and HF at 0.19–0.74 Hz and 0.78–2.5 Hz (Aubert et al. 1999), and 0.38–0.45 Hz and 1.04–1.13 Hz (Cerutti et al. 1991), respectively. The HF component is generally accepted as a marker of parasympathetic modulation (Cerutti et al. 1991; Aubert et al. 1999) and a reduction in HF power suggests a depression of the parasympathetic regulation of HR. Lo et al. (2002) demonstrated reductions of spectral power of 50% at HF and about 70% at LF and a significant decrease in LF/HF ratio in STZ-treated rats suggesting a decrease in sympathetic tone. Fazan et al. (1999) reported that HRV and HF variability of HR were reduced after chronic STZ treatment. The LF component appears to be a complicated mix of sympathetic and vagal influences and is therefore more difficult to use as a marker for either sympathetic or parasympathetic control (Bootsma et al. 1994).

Associated with the reduction in HR was a reduction in physical activity and body temperature. As was the case with HR the effects on physical activity and body temperature were rapid in onset and appeared to reach a new steady state approximately 10 days after the administration of STZ. At minimum 24-h levels of physical activity, minimum HR was markedly reduced in STZ-treated rats compared to HR in controls. Further analysis of the data shows that reductions in physical activity in STZ-treated rats preceded reductions in HR and reductions in body temperature suggesting that reduced physical activity and an associated reduction in body temperature might partly underlie the reduced HR and HRV. Shimomura et al. (1988) demonstrated reductions in ambulatory activity that was inversely correlated to blood glucose levels, and showed that metabolic abnormalities in the striatal dopaminergic neurones in STZ-treated rats may be associated with decreased ambulatory activity. Reduced body temperature may partly be explained by a reduction in calorigenic response to noradrenaline which is observed only 2 days after STZ treatment but is normalized by insulin treatment (Shibata et al. 1987).

In summary HR, HRV, physical activity and body temperature declined rapidly to a new steady state soon after the administration of STZ and remained at that level for up to 20 days. Reduced physical activity may partly underlie the reduction in HR, HRV and body temperature. Reductions in HF spectral power suggest that parasympathetic drive to the heart may be altered during the early stages of STZ-induced diabetes.

	References

Top Abstract Introduction Methods Results Discussion References

 
Aubert AE, Ramaekers D, Beckers F, Breem R, Denef C, De Van WF & Ector H (1999). The analysis of heart rate variability in unrestrained rats. Validation of method and results. Comput Methods Programs Biomed 60, 197–213.[CrossRef][Medline]

Bootsma M, Swenne CA, Van Bolhuis HH, Chang PC, Cats VM & Bruschke AV (1994). Heart rate and heart rate variability as indexes of sympathovagal balance. Am J Physiol 266, H1565–H1571.

Cerutti C, Gustin MP, Paultre CZ, Lo M, Julien C, Vincent M & Sassard J (1991). Autonomic nervous system and cardiovascular variability in rats: a spectral analysis approach. Am J Physiol 261, H1292–H1299.

Chattou S, Diacono J & Feuvray D (1999). Decrease in sodium-calcium exchange and calcium currents in diabetic rat ventricular myocytes. Acta Physiol Scand 166, 137–144.[CrossRef][Medline]

Chiou C & Zipes D (1998). Selective vagal denervation of the atria eliminates heart rate variability and baroreflex sensitivity while preserving ventricular innervation. Circulation 98, 360–368.[Abstract/Free Full Text]

Choi KM, Zhong Y, Hoit BD, Grupp IL, Hahn H, Dilly KW, Guatimosim S, Lederer WJ & Matlib MA (2002). Defective intracellular Ca(2+) signaling contributes to cardiomyopathy in Type 1 diabetic rats. Am J Physiol Heart Circ Physiol 283, H1398–H1408.[Abstract/Free Full Text]

De Angelis KL, Oliveira AR, Dall'Ago P, Peixoto LR, Gadonski G, Lacchini S, Fernandes TG & Irigoyen MC (2000). Effects of exercise training on autonomic and myocardial dysfunction in streptozotocin-diabetic rats. Braz J Med Biol Res 33, 635–641.[Medline]

Dhalla NS, Pierce GN, Innes IR & Beamish RE (1985). Pathogenesis of cardiac dysfunction in diabetes mellitus. Can J Cardiol 1, 263–281.[Medline]

Fazan R Jr, Ballejo G, Salgado MC, Moraes MF & Salgado HC (1997). Heart rate variability and baroreceptor function in chronic diabetic rats. Hypertension 30, 632–635.[Abstract/Free Full Text]

Fazan R Jr, Dias Da Silva VJ, Ballejo G & Salgado HC (1999). Power spectra of arterial pressure and heart rate in streptozotocin-induced diabetes in rats. J Hypertens 17, 489–495.[CrossRef][Medline]

Ferrari AU, Daffonchio A, Albergati F & Mancia G (1987). Inverse relationship between heart rate and blood pressure variabilities in rats. Hypertension 10, 533–537.[Abstract/Free Full Text]

Hicks KK, Seifen E, Stimers JR & Kennedy RH (1997). Diabetes with and without ketoacidosis on right atrial pacemaker rate and autonomic responsiveness. Am J Physiol 273, H1888–H1893.

Hicks KK, Seifen E, Stimers JR & Kennedy RH (1998). Effects of streptozotocin-induced diabetes on heart rate, blood pressure and cardiac autonomic nervous control. J Auton Nerv Syst 69, 21–30.[CrossRef][Medline]

Howarth FC, Qureshi MA, Bracken NK, Winlow W & Singh J. (2001). Time-dependent effects of streptozotocin-induced diabetes on contraction of ventricular myocytes from rat heart. Emirates Med J 19, 35–41.

Ishii K, Kuwahara M, Tsubone H & Sugano S (1996). Autonomic nervous function in mice and voles (Microtus arvalis): investigation by power spectral analysis of heart rate variability. Lab Anim 30, 359–364.[Abstract/Free Full Text]

Ishikawa T, Kajiwara H & Kurihara S (1999). Alterations in contractile properties and Ca²⁺ handling in streptozotocin-induced diabetic rat myocardium. Am J Physiol 277, H2185–H2194.

Kofo-Abayomi A & Lucas PD (1988). A comparison between atria from control and streptozotocin-diabetic rats: the effects of dietary myoinositol. Br J Pharmacol 93, 3–8.[Medline]

Lagadic-Gossmann D, Buckler KJLE, Prigent K & Feuvray D (1996). Altered Ca²⁺ handling in ventricular myocytes isolated from diabetic rats. Am J Physiol 270, H1529–H1537.

Li XS, Tanz RD & Chang KS (1989). Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats. Br J Pharmacol 97, 1209–1217.[Medline]

Lo GP, Careddu A, Magni G, Quagliata T, Pacifici L & Carminati P (2002). Autonomic neuropathy in streptozotocin diabetic rats: effect of acetyl-L-carnitine. Diabetes Res Clin Pract 56, 173–180.[CrossRef][Medline]

Nemeth J, Szilvassy Z, Oroszi G, Porszasz R, Jakab B & Szolcsanyi J (2001). Impaired capsaicin-induced decrease in heart rate and coronary flow in isolated heart of diabetic rats. Acta Physiol Hung 88, 207–218.[CrossRef][Medline]

Okayama H, Hamada M & Hiwada K (1994). Contractile dysfunction in the diabetic-rat heart is an intrinsic abnormality of the cardiac myocyte. Clin Sci (Colch) 86, 257–262.[Medline]

Ren J & Davidoff AJ (1997). Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes. Am J Physiol 41, H148–H158.

Shibata H, Perusse F & Bukowiecki LJ (1987). The role of insulin in nonshivering thermogenesis. Can J Physiol Pharmacol 65, 152–158.[Medline]

Shimomura Y, Shimizu H, Takahashi M, Sato N, Uehara Y, Suwa K, Kobayashi I, Tadokoro S & Kobayashi S (1988). Changes in ambulatory activity and dopamine turnover in streptozotocin-induced diabetic rats. Endocrinology 123, 2621–2625.[Abstract]

Shimoni Y, Ewart HS & Severson D (1998). Type I and II models of diabetes produce different modifications of K⁺ currents in rat heart: role of insulin. J Physiol 507, 485–496.[Abstract/Free Full Text]

Shimoni Y, Firek L, Severson D & Giles W (1994). Short-term diabetes alters K⁺ currents in rat ventricular myocytes. Circ Res 74, 620–628.[Abstract/Free Full Text]

Yu Z, Tibbits GF & McNeill JH (1994). Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding. Am J Physiol 266, H2082–H2089.

Zhang L, Parratt JR, Beastall GH, Pyne NJ & Furman BL (2002). Streptozotocin diabetes protects against arrhythmias in rat isolated hearts: role of hypothyroidism. Eur J Pharmacol 435, 269–276.[CrossRef][Medline]

	Acknowledgements

 
This project was supported by a grant from the United Arab Emirates University, Al Ain, United Arab Emirates.

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This Article Abstract Full Text (PDF) All Versions of this Article: 90/2/237    most recent expphysiol.2004.029439v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Howarth, F. C Articles by Adeghate, E Search for Related Content PubMed PubMed Citation Articles by Howarth, F. C Articles by Adeghate, E Related Collections Heart/Cardiac Muscle