Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: biochemical and histological findings

Açıkel, Mahmut; Büyükokuroğlu, Mehmet Emin; Erdoğan, Fazlı; Aksoy, Hülya; Bozkurt, Engin; Senocak, Huseyin

doi:10.1016/j.ijcard.2003.10.054

Cited by 72 publications

(50 citation statements)

References 31 publications

(32 reference statements)

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“…This value is consistent with data found in literature, pointing to the isoproterenol-induced myocardial infarction as a cause of mortality in this experimental model. Acikel et al [10] reported a mortality rate of 33.33% in rats undergone administration of isoproterenol, the approximate value found in this research.…”

Section: Discussionsupporting

confidence: 71%

“…In Figures 1 to 4, generated by this study, we present the histological classification of myocardial injury based on the study of Acikel et al [10].…”

Section: Resultsmentioning

confidence: 99%

“…The pathologist did not know which group each slide corresponded. The findings were classified into the following degrees, to compose a range of histologic myocardial injury: (0) No change: (1) Mild -focal myocyte damage or small multifocal degeneration with slight degree of inflammation, (2) Moderate -extensive myofibrillar degeneration and/or diffuse inflammatory process, (3) Severe -necrosis with diffuse inflammatory process [10].…”

Section: Histopathological Evaluationmentioning

confidence: 99%

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Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos

Filho¹,

Ferreira²,

Sousa³

et al. 2011

Rev Bras Cir Cardiovasc

101

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Objective: To evaluate and validate, in our laboratory, the essay of myocardial infarction induced by isoproterenol in rats by means of analysis of hematological, biochemical, oxidative stress markers and histopathological parameters.Methods: Thirty young, male, Wistar rats (145 to 230 g) were randomly allocated in two groups: Sham group, which underwent a virtual myocardial infarction induction, and the Infarction group, which underwent a myocardial infarction induction with isoproterenol. The administrations for the infarction induction were performed during two consecutive days and a 24-hour interval between them. Twenty-four hours after the last administration, rats from both groups were anesthetized and sacrificed for blood sample collection to evaluate complete blood count (CBC) and biochemical parameters (SGOT, SGPT, troponin I, urea and creatinin), obtain myocardial fragments for oxidative stress markers analyses (catalase activity and glutathione concentrations) as well as histopathological examinations.Results: There were no death cases in the Sham group, while the mortality rate in the Infarction group was 25%. Myocardial infarction induction with isoproterenol raised leukocytes and neutrophils counts, SGOT, troponin I and urea concentrations, reduced catalase enzyme activity and glutathione concentrations in the myocardium and let to histopathological concentrations as well. It did not exert alterations in terms of hemoglobin, SGPT and creatinin concentrations.Conclusion: The isoproterenol-induced myocardial infarction essay in rats was adequately reproduced in our laboratory, causing alterations in hematological, biochemical, oxidative stress markers and histopathological parameters. Rev Bras Cir Cardiovasc 2011;26(3):469-76 In the literature, there is a series of studies using this model, evaluating the effect of different substances on biochemical, oxidative stress markers and histopathological damage resulting from myocardial in rats [8,9]. DescriptorsThis study aims to evaluate and validate, in our environment, the model of isoproterenol inducedmyocardial infarction in rats, given the scarcity of scientific publications using this model in our country METHODS This study, whose data are from a Master

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Section: Discussionsupporting

confidence: 71%

“…In Figures 1 to 4, generated by this study, we present the histological classification of myocardial injury based on the study of Acikel et al [10].…”

Section: Resultsmentioning

confidence: 99%

Section: Histopathological Evaluationmentioning

confidence: 99%

See 1 more Smart Citation

Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos

Filho¹,

Ferreira²,

Sousa³

et al. 2011

Rev Bras Cir Cardiovasc

101

View full text Add to dashboard Cite

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“…Electrical depression and failure in the globally ischemic heart may contribute to adverse outcomes as asystole and ventricular fibrillation (7,41). The observed increased level of serum CK and troponin I in ISO-treated rats in this study was in consonance with an earlier report (1,34). Myocardial ischemia induced by isoproterenol results in deficient oxygen supply that leads to myocardial cell damage and rupture with the leakage of their enzyme content decreasing their activities in the heart of rats (21).…”

Section: Control Groupsupporting

confidence: 90%

Effect of cerebrolysin on oxidative stress-induced apoptosis in an experimental rat model of myocardial ischemia

Boshra¹,

Atwa²

2016

Physiology International

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Apoptosis plays a role in the process of tissue damage after myocardial infarction (MI). This study was designed to investigate the possible effect of cerebrolysin against apoptosis triggered by oxidative cell stress in myocardial ischemia induced by isoproterenol in rat. Rats were pretreated with cerebrolysin 5 mL/kg intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. Hearts were excised and stained to detect the infarction size. Serum levels of cardiotoxicity indices as creatine kinase isoenzyme (CK-MB) and troponin I (cTnI) as well as the cardiac oxidative stress parameters as thiobarbituric acid reactive substances and superoxide dismutase were estimated. The expression of prodeath gene p53 and antideath gene Bcl-2 was also assessed from the excised heart tissues. Leakage of cardiac enzymes, elevated oxidative stress markers, and apoptotic indices confirmed the MI occurring as a consequence of isoproterenol-induced ischemia. Cerebrolysin pretreatment caused significant attenuation of the oxidative stress-induced apoptosis in the ischemic myocardial tissue. These findings provided an evidence that cerebrolysin could protect rat myocardium against ischemic insult that was attributed to its antioxidant as well as its anti-apoptotic properties.

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“…30 It was also reported that dantrolene protects cardiac tissue against injury induced by excess β-receptor stimulation. 31 More recently, it was shown that dantrolene restores cardiac contractility by suppressing diastolic calcium leak from RyR2.…”

Section: Dantrolene Improved Hemodynamic Outcomes Postdefibrillationmentioning

confidence: 99%

Dantrolene Improves Survival After Ventricular Fibrillation by Mitigating Impaired Calcium Handling in Animal Models

et al. 2014

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Background— Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. Methods and Results— VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls ( P =0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21±6 s versus 181±57 s in controls, P =0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P =0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts ( P =0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 μmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024±0.013 versus 0.12±0.02 arbitrary unit [200-ms cycle length], P =0.001). Conclusions— Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.

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Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: biochemical and histological findings

Cited by 72 publications

References 31 publications

Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos

Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos

Effect of cerebrolysin on oxidative stress-induced apoptosis in an experimental rat model of myocardial ischemia

Dantrolene Improves Survival After Ventricular Fibrillation by Mitigating Impaired Calcium Handling in Animal Models

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