Resistance of the myocardium to ischemia and the efficacy of ischemic preconditioning in experimental diabetes mellitus

Galagudza, M. M.; Nekrasova, M K; Syrenskii, A. V.; Nifontov, E. M.

doi:10.1007/s11055-007-0040-5

Cited by 25 publications

(17 citation statements)

References 13 publications

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“…Furthermore, these data corroborate the concept of metabolic preconditioning based on the still paradoxical increase of myocardial tolerance to ischemia-reperfusion in the animals with both T1DM and T2DM [11]. …”

Section: Discussionsupporting

confidence: 81%

The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

Кравчук

Grineva

Bairamov

et al. 2011

Experimental Diabetes Research

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In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM). Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P < .01), indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s) may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.

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Section: Discussionsupporting

confidence: 81%

The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

Кравчук

Grineva

Bairamov

et al. 2011

Experimental Diabetes Research

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“…Previous data suggests that mTOR signaling might be elevated while autophagy is diminished in the hearts of hyperlipidemic Yucatan pigs [14], and we have shown that in mice diet-induced obesity results in disturbed cardiac autophagy which is accompanied by increased myocardial injury after ischemia/reperfusion [15]. Cardioprotective effects of ischemic conditioning are attenuated in the presence of cardiovascular risk factors such as aging [16, 17], diabetes [18, 19] and hyperlipidemia [20, 21]. Similarly, our previous studies demonstrated that cardioprotection by various forms of ischemic conditioning is impaired in cholesterol-fed rats [22–25].…”

Section: Introductionmentioning

confidence: 89%

Hypercholesterolemia downregulates autophagy in the rat heart

et al. 2017

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BackgroundWe have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart.MethodsMale Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot.ResultsIsolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments.ConclusionsThis is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the loss of cardioprotection reported in hypercholesterolemic animals.

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“…Alloxan was also shown to induce diabetes in fasting male Wistar (W) rats weighing 200–250 g that were given subcutaneously 125 mg/kg alloxan [94]. Galagudza et al have found that diabetic rats for six weeks were more resistant to ischemic damage compared to the myocardium of healthy animals, and ischemic preconditioning in animals with diabetes mellitus was much less effective in limiting infarct size than in control animals [94].…”

Section: Diabetes and Cardioprotective Strategiesmentioning

confidence: 99%

“…Galagudza et al have found that diabetic rats for six weeks were more resistant to ischemic damage compared to the myocardium of healthy animals, and ischemic preconditioning in animals with diabetes mellitus was much less effective in limiting infarct size than in control animals [94]. However, diabetes mellitus induced by alloxan interferes with the protective effect of postconditioning in other species [95–97].…”

Section: Diabetes and Cardioprotective Strategiesmentioning

confidence: 99%

Experimental Diabetes Mellitus in Different Animal Models

Al-awar

Kupai

Veszelka

et al. 2016

Journal of Diabetes Research

236

217

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Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

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Resistance of the myocardium to ischemia and the efficacy of ischemic preconditioning in experimental diabetes mellitus

Cited by 25 publications

References 13 publications

The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

Hypercholesterolemia downregulates autophagy in the rat heart

Experimental Diabetes Mellitus in Different Animal Models

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