Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat

VanHoose, Lisa; Sawers, Youssef; Loganathan, Rajprasad; Vacek, James L.; Stehno‐Bittel, Lisa; Novikova, Lesya; Al-Jarrah, Muhammed; Smirnova, Irina V.

doi:10.1186/1475-2840-9-56

Cited by 36 publications

(23 citation statements)

References 51 publications

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“…In addition, QRS prolongation, which may occur due to decreased CV, is found in both STZ treated rats [36] and ZDF rats [27], as well as in diabetic humans [37]. This indicates that decreased CV may be an independent risk factor for development of ventricular arrhythmias in both type 1 and 2 diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

“…Along with these systemic alterations, ZDFs also demonstrate cardiac changes such as altered myocyte contraction and Ca 2+ signaling at 9 to 13 weeks of age [23], mild diastolic dysfunction and increased collagen content at 45 weeks of age [24], as well as increased cardiac levels of triacylglycerol at 6 and 7 weeks of age [25,26]. Alterations in the ECG with the onset of diabetes in ZDF rats have also been demonstrated [27]. These alterations include widening of the QRS intervals, which may indicate decreased ventricular CV.…”

Section: Introductionmentioning

confidence: 99%

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Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

Olsen

Axelsen

Braunstein

et al. 2013

Cardiovasc Diabetol

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BackgroundDiabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown.MethodsWe used Zucker Diabetic Fatty (ZDF) rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL) rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson`s Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining.ResultsCV was significantly slower in ZDF rats (56±1.9 cm/s) compared to non-diabetic controls (ZDL, 66±1.6 cm/s), but AAP10 did not affect CV in either group. The total amount of Connexin43 (C×43) was identical between ZDF and ZDL rats, but the amount of lateralized C×43 was significantly increased in ZDF rats (42±12 %) compared to ZDL rats (30±8%), p<0.04. Judged by electrophoretic mobility, C×43 phosphorylation was unchanged between ZDF and ZDL rats. Also, no differences in cardiomyocyte size or histomorphometry including fibrosis were observed between groups, but the volume of intracellular lipid droplets was 4.2 times higher in ZDF compared to ZDL rats (p<0.01).ConclusionCV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of C×43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

Olsen

Axelsen

Braunstein

et al. 2013

Cardiovasc Diabetol

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“…In a diff erent study, VanHoose et al [ 23 ] investigated the eff ect of exercise training in obese rats using a velocity of 15 m.min − 1 for 40 min, 5 days per week for 7 weeks. These authors described signs of fatigue among the obese animals, which may suggest that those animals were in an intensity domain above their anaerobic threshold.…”

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confidence: 99%

Exercise Training at MLSS Decreases Weight Gain and Increases Aerobic Capacity in Obese Zucker Rats

et al. 2013

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This study aimed to identify the aerobic capacity enhancement and subsequent body weight (BW) status of obese Zucker rats (OZRs) after 4 weeks of treadmill running exercise at the maximal lactate steady state (MLSS). In addition to obese Zucker rats (OZRs), lean Wistar Kyoto rats (WKYs) were used, and both species were divided into control and exercise groups as follows: obese exercise (OZR-EX, n=5), obese control (OZR-CON, n=5), lean exercise (WKY-EX, n=5) and lean control (WKY-CON, n=5). The OZR and WKY exercise groups trained 5 days per week at 12.5 m.min-1 and 20 m.min-1, respectively. After 4 weeks of training, MLSS was ascertained to evaluate the animals' aerobic capacity using 3 different velocities (12.5, 15 and 17.5 m.min-1 for OZRs and 25, 30 and 35 m.min-1 for WKYs). The MLSS of OZR-EX was identified at the velocity of 15 m.min-1, representing a 20% increase in aerobic capacity after the exercise program. The MLSS of WKY-EX was identified at 30 m.min-1 with a 50% increase of in aerobic capacity. Obese animals that exercised showed reduced weight gain compared to the non-exercise obese control group (p <0.05). Our results thus show that exercise training at MLSS intensity increased the aerobic capacity in both obese and non-obese animals and also reduced BW gain.

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“…These fi ndings are of great interest since they may serve as a basis for studies involving obese animal models and physical exercise. A valuable example of the importance of MLSS in obese rats (Zucker fa/fa) is the recent study of VanHoose et al [ 19 ] , which reported that these rats showed signs of fatigue, when they were allowed to rest for a few minutes. In this study, a velocity of 15 m.min − 1 during 40 min was used.…”

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Determination of the Maximal Lactate Steady State in Obese Zucker Rats

et al. 2012

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This study aims to identify the maximum lactate steady state (MLSS) in obese rats in order to provide a more effective tool in the exercise training prescription for this important animal model. To make such determination, obese (Zucker, n=5) (390.0±18.8 g) and lean (Wistar, n=5) (227.3±26.2 g) rats were studied. After adaptation of animals to treadmill, the MLSS was determined by using 3 different velocities (10 m.min⁻¹, 12.5 m.min⁻¹ and 15 m.min⁻¹ for Zucker and 15 m.min⁻¹, 20 m.min⁻¹ and 25 m.min⁻¹ for Wistar). The MLSS was defined as the highest blood lactate concentration that increased up to 1 mmol.L⁻¹ during constant exercise. In obese rats, the MLSS was found in a velocity considerably lower than in lean controls (12.5 m.min⁻¹ and 20 m.min⁻¹), respectively (p<0.05). Therefore, the identification of MLSS in obese Zucker rats is an important tool for exercise prescription and evaluation in obese rat models.

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Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat

Cited by 36 publications

References 51 publications

Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

Exercise Training at MLSS Decreases Weight Gain and Increases Aerobic Capacity in Obese Zucker Rats

Determination of the Maximal Lactate Steady State in Obese Zucker Rats

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