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Background/aim: Epileptic seizure leads to sudden unexpected death in epilepsy (SUDEP) among affected patients. The causes of SUDEP are still unclear. The aim of this study was to research the effect of epilepsy on myocardial injury and arrhythmias during experimentally induced acute myocardial ischemia. Materials and methods: Wistar albino rats were divided into four groups: sham, pentylentetrazole (PTZ) + sham, ischemia, and PTZ + ischemia groups. PTZ (65 mg/kg, ip) was given 2 h before ischemia. Seizure scoring was conducted by evaluating the PTZ-induced behavioral changes in the rats. The left main coronary artery was ligated in anesthetized rats for 30 min. The incidence and the number of ventricular arrhythmias were determined. Histopathological scoring was performed for tissue injury by using a microscope. Results: Seizure scores were not different among the groups (P > 0.05). The incidence and number of ventricular tachycardia (VT) episodes were significantly higher in the PTZ + ischemia group than in the ischemia group (P Ë 0.05). More prominent myocardial damage was observed in the PTZ + ischemia group than in the other groups (histopathological scores: PTZ + ischemia; 2.5 ± 0.5 versus ischemia; 1.2 ± 0.4, P Ë 0.05). Conclusion: PTZ-induced seizure in rats increased myocardial injury and the incidence and number of VT episodes in myocardial ischemia. These results reveal that seizure in epilepsy patients may increase ventricular arrhythmia and myocardial injury during heart attack.
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Reperfusion of the ischemic myocardium causes the myocardial injury and life-threatening ventricular arrhythmias in human. This study aimed to investigate the effects of thymoquinone (TQ) on myocardial ischemia/reperfusion (I/R) injury and ischemia- and reperfusion-induced ventricular arrhythmias in anaesthetized rats. Adult male Wistar albino rats were divided into two groups, each containing a control and TQ-treated subgroups. In group I, the myocardial infarct size was determined by triphenyl tetrazolium chloride staining following 2-h reperfusion preceded by 30 min of ischemia. In group II, a 6-min myocardial ischemia was followed by a 10-min reperfusion. TQ-treated subgroups were treated with TQ (10 mg/100 µl/kg, i.p.) and the control subgroups were treated with the vehicle (100 µl/kg, i.p.) 20 min prior to the ischemic period. Ischemia was induced by ligating the left main coronary artery, followed by reperfusion. TQ treatment reduced the infarct size (15 ± 4% versus 69 ± 6%, P<0.01). Pretreatment with TQ decreased arrhythmia scores, as well as the incidence of ventricular tachycardia and the incidence of ventricular fibrillation during the reperfusion period (arrhythmia scores: 1.4 ± 0.3 versus 4.4 ± 0.3, P<0.01). These results suggest that TQ confers protection against myocardial I/R injury and suppresses reperfusion-induced arrhythmias.
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Benzoquinonas/farmacologia , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Nigella sativa/química , Taquicardia Ventricular/prevenção & controle , Animais , Hemodinâmica/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: 5-Lipoxygenase is an enzyme involved in the synthesis of leukotriene eicosanoids from arachidonic acid. The therapeutic potential of zileuton, an inhibitor of 5-lipoxygenase, and montelukast, a cysteinyl leukotriene receptor antagonist, for the treatment of ischemia/reperfusion (I/R) injury of the heart has been proposed in a few studies. However, the effects of zileuton and montelukast on I/R-induced arrhythmias have not been determined. OBJECTIVE: We assessed the possible protective effects of zileuton and montelukast against I/R-induced arrhythmias. METHODS: Forty-five male Wistar albino rats were divided into 5 groups, each containing 9 rats. Group 1: control, Groups 2 and 3: rats treated with montelukast (10 and 30 mg/kg IP); and Groups 4 and 5: rats treated with zileuton (1 and 3 mg/kg IV) 15 minutes before the induction of ischemia. Ischemia and reperfusion were induced by occluding the left main coronary artery of anesthetized rats for 6 minutes followed by reopening the artery for 6 minutes. RESULTS: Both doses of zileuton decreased the mean [SE] arrhythmia score (zileuton 1 mg/kg: 1.4 [0.8]; zileuton 3 mg/kg: 1.3 [0.5] vs control: 2.9 [0.3]; P < 0.05), the duration of ventricular tachycardia, and the total length of arrhythmias, but montelukast was not effective to decrease the ventricular arrhythmias during the 6 minutes of reperfusion. CONCLUSIONS: The results indicate for the first time that zileuton exerts an antiarrhythmic effect at different doses and that montelukast is not effective against I/R-induced arrhythmias. These results indicate that zileuton may be a candidate for drug treatment of I/R-induced arrhythmias.
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BACKGROUND: In the present study, we describe and show the efficacy of a lateral approach to stellate ganglion block (SGB) in rats. METHODS: Twenty-one rats were randomized into three groups: the posterior technique group (n = 7), the lateral technique group (n = 7), and the control group (n = 7). Thiopental was administered intraperitonally as 5 mg per 100 g of each rat's weight for sedation during the procedure. In the posterior technique group, SGB was performed by a posterior percutaneous approach as described previously. In the lateral technique and control groups, the cervical vertebrae was fixed between the left first and third fingers of the physician's left hand while palpating the C7 process with the second finger. The study drug was 0.2 mL 0.25% plain bupivacaine for the two percutaneous treatment groups, and 0.2 mL saline in the controls. RESULTS: Two animals in the posterior technique group died immediately after local anesthetic injection (P < 0.01). There were no deaths in the new technique group or in the controls. Ptosis appeared at 300 +/- 120 s in the posterior group, whereas it was seen almost immediately after withdrawing the needle in the lateral technique group (6 +/- 4 s) (P < 0.001). Ptosis did not occur in the control group. There was no statistically significant difference in heart rate among groups (P > 0.069). CONCLUSION: The lateral approach to SGB does not require the induction of general anesthesia. The approach is associated with early development of ptosis and may be associated with a lower mortality rate compared to the conventional posterior approach.
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Anestésicos Locais/administração & dosagem , Bloqueio Nervoso Autônomo/métodos , Bupivacaína/administração & dosagem , Bloqueadores Ganglionares/administração & dosagem , Gânglio Estrelado/efeitos dos fármacos , Animais , Blefaroptose/induzido quimicamente , Vértebras Cervicais , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Injeções Intraperitoneais , Masculino , Ratos , Ratos Sprague-Dawley , Tiopental/administração & dosagem , Fatores de TempoRESUMO
BACKGROUND: Preconditioning might protect the myocardium against ischemia/ reperfusion injury by reducing infarct size and preventing arrhythmias. Dexmedetomidine (DEX) is a highly selective α2-agonist used for sedoanalgesia in daily anesthetic practice. The cardioprotective effects of DEX on infarct size and on the incidence of arrhythmias observed after regional ischemia/reperfusion injury in vivo have not been reported. OBJECTIVE: The aim of this study was to determine whether DEX exhibits a preconditioning effect and reduces infarct size and the incidence and duration of arrhythmias in a regional cardiac ischemia/reperfusion model in rats. METHODS: Adult male Sprague-Dawley rats were anesthetized with sodium thiopental and mechanically ventilated (0.9 mL/100 g at 60 strokes/min) through a cannula inserted into the trachea after tracheotomy. Cardiac ischemia was then produced by ligating the left main coronary artery for 30 minutes, followed by a reperfusion period of 120 minutes. Blood pressure (BP) and heart rate (HR) were monitored and echocardiograms (ECGs) were performed. Arrhythmia was scored based on incidence and duration. The animals were randomly divided into 3 groups. The ischemic preconditioning (IPC) group underwent 5 minutes of ischemia followed by 5 minutes of reperfusion before the 30-minute ischemia/120-minute reperfusion period. In the DEX group, intraperitoneal (IP) DEX 1 mL (100 µg/kg) was administered 30 minutes before the ischemia/ reperfusion period. In the control group, IP saline 1 mL was administered 30 minutes before the ischemia/reperfusion period. After reperfusion, the heart was excised, demarcated with saline and ethanol to identify the occluded and nonoccluded myocardium, and cut into slices ~2 mm thick, that were then stained and placed between 2 glass plates. The risk zone and the infarct zone were compared between groups. The investigator assessing the infarcts was blinded to the study group. RESULTS: Twenty-one adult (aged 4-6 months) male Sprague-Dawley rats weighing 280 to 360 g were included in the study; 7 rats were assigned to each group. BP, HR, and ECG readings were not significantly different between groups and did not change during the study. Arrythmias occurred during ischemia and reperfusion in all groups. The duration of the arrhythmias was significantly shorter and the arrhythmia score was significantly lower in the IPC group (all, P<0.05), compared with the control group; however, they were not significantly different in the DEX group. During the ischemic period, duration of ventricular tachycardia (VT) and ventricular premature contractions (VPC) in the DEX group was significantly longer than that observed in the IPC group (all, P<0.05). The duration of VPC was also significantly shorter than that observed in the control group (both, P<0.05). Duration of VT during the reperfusion period in the DEX group was significantly longer than that observed in both IPC and control groups (both, P<0.05). The mean (SD) percentage of damage was significantly lower in the IPC group (44.1% [2.0%]) and the DEX group (26.7% [2.0%]) compared with the control group (69.0% [3.0%]; both, P<0.05). The percentage of damage in the DEX group was also significantly lower compared with the IPC group (P<0.05). CONCLUSIONS: This small, experimental in vivo study found that DEX was associated with reduced infarct size in ischemia/reperfusion injury in regional ischemia in this rat model but had no effect on the incidence of arrhythmias. Future studies are needed to clarify these findings.
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OBJECTIVE: Bupivacaine, a local anaesthetic substance, is used as a regional-anaesthesia agent. Lidocaine, a sodium channel blocker, is used in combination with epinephrine for regional anaesthesia. We aimed to evaluate the effects of lidocaine with epinephrine (LE) at different doses on bupivacaine-induced cardiotoxicity in rats. METHODS: In our study, 24 Wistar albino rats were divided into four groups: I) Control; II) LE, 1 mg kg-1; III) LE, 3 mg kg-1 and IV) LE, 6 mg kg-1. Intravenous bupivacaine was administered at a dose of 3 mg kg-1 min-1 to the anaesthetized rats in all groups until cardiac asystole was achieved. LE was administered at the doses of 1, 3 and 6 mg kg-1 min-1 using infusion, simultaneously with bupivacaine. The asystole time and 75% decrement time in mean arterial blood pressure (MABP) were determined. P-Q, Q-T and QRS intervals were measured using electrocardiography (ECG) recordings. RESULTS: LE significantly increased the asystole time and 75% decrement time in MABP at the doses of 3 and 6 mg kg-1 compared to the control group (p<0.05) and significantly increased these values at the dose of 1 mg kg-1 compared to the control and other treatment groups (p<0.05). LE abolished the prolongation of P-Q, Q-T and QRS intervals in ECG recordings at the dose of 1 mg kg-1 (p<0.05). CONCLUSION: These results reveal that LE has a protective effect against bupivacaine cardiotoxicity. In clinical application, the simultaneous application of LE and bupivacaine may reduce the risk of cardiotoxicity due to bupivacaine.
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'Compound A' (4(i)-(N-(4-acetamidobenzyl))-2,2-dimethyl-2,3-dihydro-5(i)H-spiro[chromene-4,2(i)-[1,4]oxazinan]-5(i)-one) is a new spiro-cyclic benzopyran activator of the mitochondrial ATP-dependent potassium channels (mitoKATP). We researched the effect of compound A on ischemia/reperfusion (I/R)-induced ventricular arrhythmias. We also tested the hypothesis that the application of the activation of mitoKATP in combination with the inhibition of sarcolemmal ATP-dependent potassium channels (sarcKATP) may produce a stronger antiarrhythmic effect. In anesthetized rats, myocardial ischemia was performed by ligating the left main coronary artery followed by reperfusion. At a dose of 10 mg/kg, compound A significantly decreased arrhythmia scores and the total length of arrhythmias, whereas this was found to be ineffective at a dose of 3 mg/kg. Pre-treatment with 5-HD, a selective mitoKATP blocker, abolished the antiarrhythmic effect of compound A. Both diazoxide, a selective mitoKATP opener and HMR 1098, a selective sarcKATP blocker, significantly decreased the total length of arrhythmias. However, the combination of neither diazoxide nor compound A with HMR 1098 showed no additional therapeutic benefit. These results reveal that compound A may have a dose-dependent antiarrythmic effect, which is more pronounced than the antiarrhythmic effect of diazoxide. The antiarrhythmic effect of compound A may possibly depend on mitoKATP activation.
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Antiarrítmicos/farmacologia , Benzopiranos/agonistas , Mitocôndrias Cardíacas/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio , Animais , Antiarrítmicos/química , Benzopiranos/química , Relação Dose-Resposta a Droga , Masculino , Mitocôndrias Cardíacas/fisiologia , Bloqueadores dos Canais de Potássio/química , Canais de Potássio/fisiologia , Ratos , Ratos WistarRESUMO
BACKGROUND/AIM: To investigate the influence of thiopental (85 mg/kg, intraperitoneally (ip)), and ketamine+xylazine (ketamine 75 mg/kg and xylazine 8 mg/kg, ip) anesthesia on the incidence and duration of ischemia/reperfusion-induced arrhythmias. MATERIALS AND METHODS: Myocardial ischemia was induced by a 6-min ligation of the left anterior descending coronary artery, followed by a 6-min reperfusion. Measurements were taken of the incidence and duration of ventricular arrhythmias, the mean arterial blood pressure and heart rate, and the pressure rate-product (as an.index of myocardial oxygen consumption). RESULTS: The arrhythmia score and the incidence of ventricular fibrillation and tachycardia were significantly decreased in the ketamine+xylazine-anesthetized rats compared with the thiopental-anesthetized group (arrhythmia score: 2.0 ± 2.1 versus 3.7 ± 1.2, P < 0.05). The heart rate was significantly lower in the ketamine+xylazine group during the entire experiment, whilst the pressure-rate product was also significantly lower in the ketamine+xylazine group at different time points of the ischemia and reperfusion periods. CONCLUSION: Ketamine+xylazine anesthesia has a strong antiarrhythmic effect and an apparent depressive action on the heart rate and the myocardial oxygen consumption index. Therefore, ketamine+xylazine anesthesia is not appropriate for the evaluation of possible antiarrhythmic agents. Thiopental anesthesia is preferable to ketamine+xylazine anesthesia in the in vivo ischemia-reperfusion arrhythmia model.
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Anestésicos Combinados/farmacologia , Arritmias Cardíacas/prevenção & controle , Ketamina/farmacologia , Tiopental/farmacologia , Xilazina/farmacologia , Anestésicos Intravenosos/farmacologia , Animais , Arritmias Cardíacas/etiologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/complicações , Consumo de Oxigênio/efeitos dos fármacos , Ratos WistarRESUMO
Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid with anti-inflammatory activity mediated by enhancing adenosine signaling. As the adenosine A1 receptor activation confers protection against ischemia/reperfusion (I/R)-induced ventricular arrhythmias, we hypothesized that CBD may have antiarrhythmic effect through the activation of adenosine A1 receptor. Cannabidiol has recently been shown to suppress ischemia-induced ventricular arrhythmias. We aimed to research the effect of CBD on the incidence and the duration of I/R-induced ventricular arrhythmias and to investigate the role of adenosine A1 receptor activation in the possible antiarrhythmic effect of CBD. Myocardial ischemia and reperfusion was induced in anesthetized male rats by ligating the left anterior descending coronary artery for 6 minutes and by loosening the bond at the coronary artery, respectively. Cannabidiol alone was given in a dose of 50 µg/kg, 10 minutes prior to coronary artery occlusion and coadministrated with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) in a dose of 100 µg/kg, 15 minutes prior to coronary artery occlusion to investigate whether the antiarrhythmic effect of CBD is modified by the activation of adenosine A1 receptors. The experimental groups were as follows: (1) vehicle control (n = 10), (2) CBD (n = 9), (3) DPCPX (n = 7), and (4) CBD + DPCPX group (n = 7). Cannabidiol treatment significantly decreased the incidence and the duration of ventricular tachycardia, total length of arrhythmias, and the arrhythmia scores compared to control during the reperfusion period. The DPCPX treatment alone did not affect the incidence and the duration of any type of arrhythmias. However, DPCPX aborted the antiarrhythmic effect of CBD when it was combined with it. The present results demonstrated that CBD has an antiarrhythmic effect against I/R-induced arrhythmias, and the antiarrhythmic effect of CBD may be mediated through the activation of adenosine A1 receptor.
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Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Canabidiol/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptor A1 de Adenosina/fisiologia , Animais , Antiarrítmicos/farmacologia , Arritmias Cardíacas/metabolismo , Canabidiol/farmacologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
AIM: this study was performed to assess the effect of selective sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) channel (K(ATP)) inhibition and the mitochondrial K(ATP) channel activation on ischemia and reperfusion (I/R)-induced arrhythmias in different gender of rats. We compared the effect of a selective sarcolemmal K(ATP) channel blocker HMR 1098, a selective mitochondrial K(ATP) channel opener diazoxide, a nonselective K(ATP) channel opener pinacidil, and the combination of pinacidil with HMR 1098 on the incidence and duration of ventricular arrhythmias in 2 groups: anesthetized males (n = 31) and females (n = 31). MAIN METHODS: ischemia and reperfusion was produced by occluding the left main coronary artery of Sprague-Dowley rats for 6 minutes followed by re-opening of the artery for 6 minutes. KEY FINDINGS: the arrhythmia score and the duration of arrhythmias were significantly reduced by HMR 1098, diazoxide, and pinacidil in male rats. The combination of the pinacidil with HMR 1098 did not change the antiarrhythmic effect of pinacidil. The duration of arrhythmas was shorter in females than that in the corresponding males. Drug treatments were not effective in decreasing arrhythmias in female groups to the same extent as in the male group. However, the mitochondrial K( ATP) channel activation that is provided by the combination of pinacidil with HMR 1098 significantly decreased the total length of arrhythmias in females. SIGNIFICANCE: results of the current study indicate that both mitochondrial K(ATP) channel activation and sarcolemmal K(ATP) channel inhibition exert antiarrhythmic action in male rats. The antiarrhythmic effect of pinacidil is not depend on the sarcolemmal K(ATP) channel opening. These results also indicate that K(ATP) channel modulators show no discernable effect in female rats due to the already low incidence of arrhythmias in females.
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Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Canais KATP/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Benzamidas/farmacologia , Diazóxido/farmacologia , Feminino , Canais KATP/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Pinacidil/farmacologia , Ratos , Ratos Sprague-Dawley , Sarcolema/efeitos dos fármacos , Sarcolema/metabolismo , Caracteres SexuaisRESUMO
OBJECTIVE: To investigate the role of stellate ganglion blockade (SGB) in cardio-protection against ischemia reperfusion injury. METHODS: This prospective randomized, experimental study was carried out between August and October 2008 in the Department of Anesthesia, Abant Izzet Baysal University, Bolu, Turkey. Twenty-one rats were randomly divided into 3 groups; group 1--SGB group (rats with percutaneous ganglion blockade), group 2--preconditioned (P) group (rats that were subjected to ischemia and then reperfusion periods for 5 minutes), and group 3--control group (rats that were injected with normal saline). RESULTS: During the ligation period, the length of arrhythmia was significantly shorter in group 2 compared with group 3 (p<0.001). The arrhythmia score in groups 1 and 2 was significantly lower compared with group 3 (p<0.001). In the reperfusion period, the length of arrhythmia was not significantly different in all study groups (p>0.05). But the arrhythmia score was significantly lower both in group 1 and group 3, compared with group 2 (p<0.02). Both in the ischemic and reperfusion periods, the incidence of arrhythmia was lowest in group 1. The infarct size was measured significantly less in groups 1 and 2 compared with group 3 (p<0.001). CONCLUSION: Pretreatment with the left SGB leads to lower arrhythmia scores and reduced infarct size in the Langendorff-perfused rat hearts compared with group 3, but not with group 2.
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Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/prevenção & controle , Gânglio Estrelado , Animais , Masculino , Infarto do Miocárdio/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Thiol-modifying agents induce the release of nitric oxide (NO) from endothelial epithelium and the release of reactive oxygen free radicals in the vascular system. Moreover, thiol groups are essential for the functioning of the ATP dependent potassium channel (K-ATP). The effects of thiol-modifying agents and their molecular mechanisms on arrhythmia have not been widely studied. In this study, we investigated the effect of the hydrophilic SH-group-oxidizing substance thimerosal on the arrhythmia induced by reperfusion/ischemia after coronary artery ligation in rats. We studied the possible involvement of the K-ATP and NOS on the effect of thimerosal. Thimerosal pretreatment (3, 30 mg/kg dose iv. 10 minutes before coronary occlusion) significantly decreased the length of total arrhythmia, ventricular tachycardia, and the arrhythmia score. This effect of thimerosal was reversed by the K-ATP opener pinacidil but not by the K-ATP blocker glibenclamide. The inhibition of iNOS by L-NAME did not alter the antiarrhythmic effect of thimerosal. These data clearly suggest that the antiarrhythmic effect of thimerosal is dependent upon the blockage of K-ATP.