| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology2 College Requirements Unit, Faculty of Engineering3 Department of Pharmacology, Faculty of Medicine & Health Sciences4 Department of Anatomy, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
(Received 10 June 2005;
accepted after revision 2 August 2005; first published online 9 August 2005)
Corresponding author F. C. Howarth: Department of Physiology, Faculty of Medicine & Health Sciences, PO Box 17666, Al Ain, United Arab Emirates. Email: chris.howarth{at}uaeu.ac.ae
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In this study, a biotelemetry system was employed to further investigate the progressive long-term effects of STZ-induced diabetes on the ECG. The relationship between changes in HR, physical activity and body temperature in diabetic rats was also investigated.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Heart biopotential, physical activity and body temperature were monitored using a biotelemetry 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 personal computer for system configuration, control, acquisition and storage. The transmitter devices were surgically implanted in 10 young adult male Wistar rats (220–230 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 the Einthoven bipolar lead II configuration (right foreleg and left hindleg). Animals were allowed to recover from surgery and the effects of anaesthesia for a period of 1 week, after which the transmitters in the animals were activated by use of a magnet switch. Data recording was started 1 week before the induction of diabetes. Ethical approval for the project was obtained from the Faculty of Medicine & Health Sciences Ethics Committee for Animal Research, United Arab Emirates University.
Induction of diabetes
After 10 days of biotelemetry data collection, diabetes was induced in five of the 10 rats by a single intraperitoneal injection of STZ (60 mg (kg body weight)–1; Sigma, St Louis, MO, USA). The STZ was dissolved in a citrate buffer solution (0.1 mol l–1 citric acid, 0.1 mol l–1 sodium citrate; pH 4.5). Five age-matched controls received an equivalent volume of the citrate buffer solution alone. Body weight and blood glucose were measured periodically throughout the study.
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 22 week study. Data recording commenced 1 week before the administration of STZ (pretreatment period) and continued thereafter for the remainder of the experimental period. 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 0.05 were considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The general characteristics of STZ-treated rats included reduced body weight gain (Fig. 1A) and elevated blood glucose levels (Fig. 1B) compared to age-matched controls. At 4 weeks after STZ treatment, the blood glucose level in diabetic rats was 292 ± 36 mg dl–1 compared to 76 ± 6 mg dl–1 in controls and at 24 weeks, blood glucose level in diabetic rats was 252 ± 9 mg dl–1 (n = 5) compared to 66 ± 6 mg dl–1 (n = 5) in controls. The initial weight of the experimental animals prior to transmitter implantation was 235 ± 2 g (n = 10). The rate of body weight gain in diabetic rats was significantly less than in age-matched controls. At 4 weeks after STZ treatment, the body weight in diabetic rats was 248 ± 12 g (n = 5) compared to 305 ± 20 g (n = 5) in controls and at 24 weeks, the body weight in diabetic rats was 308 ± 14 g (n = 5) compared to 410 ± 20 g (n = 5) in controls.
|
The HR was determined from the 5-min average of all normal R–R intervals in the ECG. The effects of STZ treatment on HR are shown in Fig. 2A. HR fell rapidly and dramatically after administration of STZ (Fig. 2A). At 4 weeks after induction of diabetes, HR was 268 ± 5 beats min–1 (n = 5) in STZ-treated rats compared to 347 ± 12 beats min–1 (n = 5) in age-matched controls, and at 22 weeks HR was 266 ± 5 beats min–1 (n = 5) in diabetic rats compared to 316 ± 6 beats min–1 (n = 5) in controls (Fig. 2B). The effects of short-term STZ treatment on various cardiac cycle intervals are shown in Fig. 3. The QRS interval is the time from the Q-point to the S-point of the QRS complex and the QT interval is the time from the Q-point to the end of the T-wave. QRS (Fig. 3A and B) and QT (Fig. 3C and D) intervals were longer in diabetic rats compared to controls at all measured time points between 4 and 22 weeks; however, the differences did not reach statistical significance (P > 0.05).
|
|
The HRV was computed as the standard deviation (STD) of the average of normal-to-normal beats (SDANN). The SDANN was computed by first determining the 5-min average HR for each animal every hour. Then, the STD of 12 previous HR averages and 12 subsequent HR averages was computed in order to determine the 24-h HRV. Figure 4 shows the effects of STZ treatment on SDANN-defined HRV. The HRV during the pretreatment period in rats that were to receive STZ (26 ± 4 beats min–1, n = 5) was not significantly (P > 0.05) different from controls (24 ± 4 beats min–1, n = 5). HRV declined after the administration of STZ (Fig. 4A). At 4 weeks after induction of diabetes, HRV was 18 ± 3 beats min–1 (n = 5) in STZ-treated rats compared to 33 ± 3 beats min–1 (n = 5) in age-matched controls, and at 22 weeks HRV was 20 ± 4 beats min–1 (n = 5) in diabetic rats compared to 25 ± 4 beats min–1 (n = 5) in controls (Fig. 4B).
|
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 period of HRV during the pretreatment period and at 4, 8, 12, 16 and 22 weeks after STZ-treatment (Fig. 5A–F). 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. The most obvious effect was a decrease in HRV PSD at high frequencies (2.5–3.5 Hz) in diabetic rats at 4, 8, 12, 16 and 22 weeks after STZ treatment compared to controls (Fig. 5B–F). The low frequency/high frequency (LF/HF) ratio was increased in diabetic rats compared to controls with significant increases (P < 0.05) at 4 and 8 weeks after STZ treatment (Fig. 5G).
|
Physical activity was assessed by measuring changes in the animal's transmitter signal strength. The transmitter signal strength was sampled at 64 Hz and calibrated to counts min–1. When the animal changes its position, the corresponding transmitter signal strength is changed, which results in a change in counts min–1. Low counts indicate reduced physical activity in the animal. Figure 6A shows the effects of STZ treatment on physical activity. Physical activity declined after administration of STZ (Fig. 6B). At 4 weeks after induction of diabetes, physical activity was 0.49 ± 0.07 counts min–1 (n = 5) in STZ-treated rats compared to 1.48 ± 0.10 counts min–1 (n = 5) in age-matched controls and at 22 weeks, physical activity was 0.69 ± 0.22 counts min–1 (n = 5) in diabetic rats compared to 1.19 ± 0.17 counts min–1 (n = 5) in controls.
|
In addition to ECG and physical activity, the implant transmits the animal's body temperature. As for HR, the temperature was measured and recorded each hour. The effects of STZ treatment on body temperature are shown in Fig. 7. The 24-h computed average body temperature declined after administration of STZ (Fig. 7B). At 4 weeks after induction of diabetes, body temperature was 37.0 ± 0.1°C (n = 5) in STZ-treated rats compared to 37.5 ± 0.1°C (n = 5) in age-matched controls and at 22 weeks body temperature was 37.1 ± 0°C (n = 5) in diabetic rats compared to 37.4 ± 0.1°C (n = 5) in controls.
|
To assess the effects of insulin on HR, physical activity and body temperature, long acting insulin (Ultralente, 5–8 units daily, subcutaneous) was administered to three of the STZ-treated rats at the end of the study for a period of 3 weeks. HR was 329 ± 14 beats min–1 prior to administration of STZ, 266 ± 6 beats min–1 at 22 weeks after STZ treatment and 288 ± 12 beats min–1 after 3 weeks of insulin. This represents a 10% average increase in HR due to insulin administration. Respective values were 0.96 ± 0.12, 0.69 ± 0.29 and 0.84 ± 0.31 counts min–1 for physical activity, and 37.5 ± 0.0, 37.1 ± 0.1 and 37.4 ± 0.1°C for body temperature.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
STZ-induced diabetes was characterized by a 4- to 5-fold increase in blood glucose level and a marked reduction in the rate of body weight gain. Other well documented characteristics include polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinaemia and hyperglycaemia (Hakim et al. 1997). Previous studies have demonstrated that STZ-induced diabetes is associated with an initial hypophagia and then, as animals lose weight, a significant hyperphagia. The increase in food consumption may partly be attributed to STZ-induced hypoinsulinaemia and perhaps more importantly to hypoleptinaemia (Tepper & Kanarek, 1985; Vanderweele, 1993; Hidaka et al. 2001). An inability to metabolize carbohydrate fuel sources leads to a shift in reliance to fatty fuels and this causes a wasting of fat stores and loss of weight, and reductions in the rate of weight gain compared to age-matched controls.
HR and HRV were significantly reduced at 4 weeks after STZ treatment compared to age-matched controls, but were not additionally altered during the remainder of the 22-week study. The mechanisms underlying reduced HR in diabetic rats may include defects in control mechanisms that are either intrinsic and/or extrinsic to the heart. Several studies, including experiments in our own laboratory, have demonstrated reductions of HR in various isolated heart preparations from STZ-treated rats and the magnitude of the negative 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). Reductions in basal spontaneous rate have also been reported in superfused right atrial preparations at 12 weeks after STZ treatment, which may suggest a specific impairment of sinoatrial node function (Kofo-Abayomi & Lucas, 1988; Hicks et al. 1997). Taken together, these data suggest that intrinsic defects may at least partly underlie the reduced HR seen in STZ-induced diabetic rats. 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).
It is worth noting that there was a small progressive decline of HR in age-matched controls which became evident 12 weeks into the experiment. Several previous studies carried out in vivo and in isolated heart preparations have demonstrated age-dependent declines in HR, which may be partly due to changes in pacemaker activity of the heart as well as adrenergic control (Goldberg et al. 1988; Schmidlin et al. 1992; Irigoyen et al. 2000). In diabetic rats, despite the rapid and dramatic reductions in HR, the mean arterial pressure tends to be well maintained by minimizing cardiac output reduction via slight increases in stroke volume and concomitant small increases in total peripheral resistance (Dowell et al. 1986).
The QRS and QT intervals on the ECG were prolonged in STZ-treated rats although the effects did not reach statistical significance. The QT interval provides a measure of the electrical events associated with depolarization and then repolarization of the ventricles. In the clinical setting, prolonged QT interval is considered to be an indicator of increased risk of malignant ventricular arrhythmias and/or sudden death and it has been proposed that autonomic neuropathy in diabetes is related to QT interval prolongation and therefore increased mortality rates (Veglio et al. 2000, 2004; Rossing et al. 2001). Prolongation of the action potential duration has been reported to occur within 4–6 days after the administration of STZ (Shimoni et al. 1994). The underlying causes of the prolongation may include slowed inactivation of the L-type Ca2+ current and/or reductions in Ca2+-independent transient outward K+ current and steady-state outward K+ current (Nobe et al. 1990; Jourdon & Feuvray, 1993; Shimoni et al. 1994, 1995; Casis et al. 2000; Pandit et al. 2003; Raimondi et al. 2004), and the effects of STZ-induced diabetes on different ionic currents may vary in different regions of the heart (Shimoni et al. 1995).
The HRV, an index of sympathovagal modulation of heart function (Aubert et al. 1999; Ferrari et al. 1987; Bootsma et al. 1994), declined rapidly after STZ treatment (Lo et al. 2002; Fazan et al. 1997); this may be indicative of defective autonomic regulation of heart function. Power spectral analysis showed a decrease in power at HF (2.5–3 Hz) in diabetic rats at 4 weeks after STZ treatment suggesting altered parasympathetic drive to the heart. LF/HF ratio was significantly increased at 4 weeks after STZ treatment providing additional evidence for a disturbance in the sympathovagal balance (Chiou & Zipes, 1998). The boundaries for LF and HF are not clearly defined in the literature. The LF and HF bands were set at 0.1–1.0 Hz and 1.0–5.0 Hz, respectively, by Ishii et al. (1996) for studies in mice and voles, and at 0.19–0.74 Hz and 0.78–2.5 Hz, respectively, by Aubert et al. (1999) and 0.38–0.45 Hz and 1.04–1.13 Hz, respectively, by Cerutti et al. (1991) in rat. 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).
Reductions in physical activity and body temperature were associated with the reduction in HR. The effects were dramatic and rapid and reached a new low steady state 1–2 weeks after STZ treatment and were not further altered during the remainder of the 22-week study. Further analysis showed that reductions in physical activity in STZ-treated rats preceded reductions in HR and reductions in body temperature. Physical activity began to fall approximately 1 day after STZ treatment and approximately 2–2.5 days after treatment, the HR and body temperature dropped almost simultaneously. These findings suggest that reduced physical activity might partly underlie the early reductions in HR and HRV. Shimomura et al. (1988) demonstrated reductions in ambulatory activity that were inversely correlated with blood glucose levels; they also demonstrated 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 has been reported to occur only 2 days after STZ treatment (Shibata et al. 1987; Zhang et al. 2002).
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 the remainder of the study period. Reduced physical activity may partly underlie the reduction in HR, HRV and body temperature. Increased LF/HF ratio and reductions in HF spectral power suggest the presence of sympathovagal imbalance and in particular that parasympathetic drive to the heart may be altered during the early stages of STZ-induced diabetes. The effects of STZ treatment on HR, physical activity and body temperature were partially normalized by insulin treatment.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Booth RJ & Hodgson WC (1993). Effects of aldose reductase inhibition with epalrestat on diabetes-induced changes in rat isolated atria. Clin Exp Pharmacol Physiol 20, 207–213.[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.
Casis O, Gallego M, Iriarte M & Sanchez-Chapula JA (2000). Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle. Diabetologia 43, 101–109.[CrossRef][Medline]
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.
Choi KM, Zhong Y, Hoit BD, Grupp IL, Hahn H, Dilly KW, Guatimosim S, Lederer WJ & Matlib MA (2002). Defective intracellular Ca2+ signaling contributes to cardiomyopathy in Type 1 diabetic rats. Am J Physiol Heart Circ Physiol 283, H1398–H1408.
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]
Dowell RT, Atkins FL & Love S (1986). Integrative nature and time course of cardiovascular alterations in the diabetic rat. J Cardiovasc Pharmacol 8, 406–413.[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.
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.
Goldberg PB, Tumer N & Roberts J (1988). Effect of increasing age on adrenergic control of heart rate in the rat. Exp Gerontol 23, 115–125.[Medline]
Goyal RK & McNeill JH (1985). Effects of chronic streptozotocin-induced diabetes on the cardiac responses to milrinone. Can J Physiol Pharmacol 63, 1620–1623.[Medline]
Hakim ZS, Patel BK & Goyal RK (1997). Effects of chronic ramipril treatment in streptozotocin-induced diabetic rats. Indian J Physiol Pharmacol 41, 353–360.[Medline]
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]
Hidaka S, Yoshimatsu H, Kondou S, Oka K, Tsuruta Y, Sakino H et al. (2001). Hypoleptinemia, but not hypoinsulinemia, induces hyperphagia in streptozotocin-induced diabetic rats. J Neurochem 77, 993–1000.[CrossRef][Medline]
Howarth
FC, Jacobson
M, Naseer
O
&
Adeghate
E (2005). Short-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats. Exp Physiol
90, 237–245.
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.
Imai M, Chang KS, Tanz RD, Stevens WC & Kemmotsu O (1991). Enhanced myocardial depression from bupivacaine in diabetic rats. Masui 40, 868–872.[Medline]
Irigoyen
MC, Moreira
ED, Werner
A, Ida
F, Pires
MD, Cestari
IA
&
Krieger
EM (2000). Aging and baroreflex control of RSNA and heart rate in rats. Am J Physiol Regul Integr Comp Physiol
279, R1865–R1871.
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.
Jourdon
P
&
Feuvray
D (1993). Calcium and potassium currents in ventricular myocytes isolated from diabetic rats. J Physiol
470
411–429.
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 KJ, Le 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]
Nagamine F, Murakami K, Mimura G & Sakanashi M (1989). Effects of beta-adrenoceptor blocking agents on isolated atrial and papillary muscles from experimentally diabetic rats. Jpn J Pharmacol 49, 67–76.[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]
Nicholl TA, Lopaschuk GD & McNeill JH (1991). Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart. Am J Physiol 261, H1053–H1059.
Nobe
S, Aomine
M, Arita
M, Ito
S
&
Takaki
R (1990). Chronic diabetes mellitus prolongs action potential duration of rat ventricular muscles: circumstantial evidence for impaired Ca2+ channel. Cardiovasc Res
24, 381–389.
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]
Pandit
SV, Giles
WR
&
Demir
SS (2003). A mathematical model of the electrophysiological alterations in rat ventricular myocytes in type-I diabetes. Biophys J
84, 832–841.
Raimondi
L, De Paoli
P, Mannucci
E, Lonardo
G, Sartiani
L, Banchelli
G, Pirisino
R, Mugelli
A
&
Cerbai
E (2004). Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats. Diabetes
53, 1927–1933.
Ramanadham S & Tenner TEJ (1986). Chronic effects of streptozotocin diabetes on myocardial sensitivity in the rat. Diabetologia 29, 741–748.[CrossRef][Medline]
Ravingerova T, Styk J, Pancza D, Tribulova N, Sebokova J, Volkovova K, Ziegelhoffer A & Slezak J (1996). Diabetic cardiomyopathy in rats: alleviation of myocardial dysfunction caused by Ca2+ overload. Diabetes Res Clin Pract 31, S105–S112.
Ren J & Davidoff AJ (1997). Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes. Am J Physiol 41, H148–H158.
Rossing P, Breum L, Major-Pedersen A, Sato A, Winding H, Pietersen A, Kastrup J & Parving HH (2001). Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus. Diabet Med 18, 199–205.[CrossRef][Medline]
Schmidlin O, Bharati S, Lev M & Schwartz JB (1992). Effects of physiological aging on cardiac electrophysiology in perfused Fischer 344 rat hearts. Am J Physiol 262, H97–H105.[Medline]
Sellers DJ & Chess-Williams R (2000). The effects of streptozotocin-induced diabetes and aldose reductase inhibition with sorbinil, on left and right atrial function in the rat. J Pharm Pharmacol 52, 687–694.[CrossRef][Medline]
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, Firek
L, Severson
D
&
Giles
W (1994). Short-term diabetes alters K+ currents in rat ventricular myocytes. Circ Res
74, 620–628.
Shimoni Y, Severson D & Giles W (1995). Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle. J Physiol 488, 673–688.[Medline]
Tepper BJ & Kanarek RB (1985). Dietary self-selection patterns of rats with mild diabetes. J Nutr 115, 699–709.
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.
Vanderweele DA (1993). Insulin and satiety from feeding in pancreatic-normal and diabetic rats. Physiol Behav 54, 477–485.[Medline]
Veglio M, Chinaglia A & Cavallo PP (2000). The clinical utility of QT interval assessment in diabetes. Diabetes Nutr Metab 13, 356–365.[Medline]
Veglio M, Chinaglia A & Cavallo-Perin P (2004). QT interval, cardiovascular risk factors and risk of death in diabetes. J Endocrinol Invest 27, 175–181.[Medline]
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 article has been cited by other articles:
|
|
 |
|
  S. Park, B. J. Bivona, Y. Feng, E. Lazartigues, and L. M. Harrison-Bernard Intact renal afferent arteriolar autoregulatory responsiveness in db/db mice Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1504 - F1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Howarth, M. Jacobson, M. Shafiullah, and E. Adeghate Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat Exp Physiol, March 1, 2008; 93(3): 362 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rouyer, J. Zoll, F. Daussin, C. Damge, P. Helms, S. Talha, L. Rasseneur, F. Piquard, and B. Geny Muscle: Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats Exp Physiol, November 1, 2007; 92(6): 1047 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nygren, M. L. Olson, K. Y. Chen, T. Emmett, G. Kargacin, and Y. Shimoni Propagation of the cardiac impulse in the diabetic rat heart: reduced conduction reserve J. Physiol., April 15, 2007; 580(2): 543 - 560. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
