ABSTRACT
Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.
Subject(s)
Antioxidants/therapeutic use , Apoptosis/drug effects , Limonene/therapeutic use , Myocardial Infarction/drug therapy , Reactive Oxygen Species/metabolism , Animals , Apoptosis Regulatory Proteins/drug effects , Apoptosis Regulatory Proteins/metabolism , Electrocardiography/drug effects , Long QT Syndrome/prevention & control , Male , Mice , Molecular Structure , Oxidative Stress/drug effects , Superoxide Dismutase/metabolismABSTRACT
Abstract Introduction: Severe obstructive sleep apnea is associated with increased QT corrected interval dispersion and continuous positive airway pressure is thought to improve this arrhythmogenic marker. Objective: The aim of the study was to determine the decrease of ratio of cardiovascular risk in patients with obstructive sleep apnea. Methods: The study included 65 patients with severe obstructive sleep apnea who had an apnea-hypopnea index score of >30. Each patient underwent 12-channel electrocardiogram monitoring and polysomnography. Patients with an apnea-hypopnea index score of <5 were used as the control group. The control group also underwent electrocardiogram monitoring and polysomnography testing. The QT corrected interval dispersion levels of both groups were calculated. Three months after continuous positive airway pressure treatment, electrocardiogram recordings were obtained from the 65 patients with severe obstructive sleep apnea again, and their QT corrected interval dispersion values were calculated. Results: There were 44 male and 21 female patients with severe obstructive sleep apnea syndrome. The age, gender, body mass index, initial saturation, minimum saturation, average saturation, and desaturation index were determined in both groups. The QT corrected intervals of the obstructive sleep apnea patients (62.48 ± 16.29 ms) were significantly higher (p = 0.001) than those of the control group (29.72 ± 6.30 ms). There were statistically significant differences between the QT corrected values before and after the continuous positive airway pressure treatment, with pretreatment QT corrected intervals of 62.48 ± 16.29 ms and 3-month post-treatment values of 41.42 ± 16.96 ms (p = 0.001). There was a positive and significant correlation between QT corrected interval dispersion periods and the apnea-hypopnea index and hypopnea index in obstructive sleep apnea patients (p = 0.001; r = 0.71; p = 0.001; r = 0.679, respectively). Conclusion: Continuous positive airway pressure treatment reduced the QT corrected interval dispersion in patients with severe obstructive sleep apnea. In addition, shortening the QT corrected interval dispersion periods in patients with severe obstructive sleep apnea may reduce their risk of arrhythmias and cardiovascular disease.
Resumo Introdução: A apneia obstrutiva do sono grave está associada a uma maior dispersão do intervalo QT corrigido e acredita-se que a pressão positiva contínua nas vias aéreas melhore esse marcador arritmogênico. Objetivo: Determinar a diminuição da razão de risco cardiovascular em pacientes com apneia obstrutiva do sono. Método: O estudo incluiu 65 pacientes com apneia obstrutiva do sono grave que apresentavam índice de apneia-hipopneia > 30. Cada paciente foi submetido à monitoração por eletrocardiograma de 12 derivações e polissonografia. Os pacientes com escore de índice de apneia-hipopneia < 5 foram utilizados como o grupo de controle. O grupo de controle também foi submetido à monitoração por eletrocardiograma e teste de polissonografia. Os níveis de dispersão do intervalo QT corrigido dos dois grupos foram calculados. Três meses após o tratamento com pressão positiva contínua nas vias aéreas, os registros de eletrocardiograma foram novamente obtidos dos 65 pacientes com apneia obstrutiva do sono grave e seus valores de dispersão do intervalo QT corrigido foram calculados. Resultados: Havia 44 pacientes do sexo masculino e 21 do feminino com síndrome de apneia obstrutiva do sono grave. Idade, sexo, índice de massa corporal, saturação inicial, saturação mínima, saturação média e índice de dessaturação foram determinados em ambos os grupos. Os intervalos QT corrigido dos pacientes com apneia obstrutiva do sono (62,48 ± 16,29 ms) foram significativamente maiores (p = 0,001) do que os do grupo controle (29,72 ± 6,30 ms). Houve diferenças estatisticamente significativas entre os valores de QT corrigido antes e após o tratamento com pressão positiva contínua nas vias aéreas, com intervalos QT corrigido pré-tratamento de 62,48 ± 16,29 ms e três meses pós-tratamento, de 41,42 ± 16,96 ms (p = 0,001). Houve uma correlação positiva e significativa entre os períodos de dispersão do intervalo QT corrigido e o índice de apneia-hipopneia e índice de hipopneia em pacientes com apneia obstrutiva do sono (p = 0,001; r = 0,71; p = 0,001; r = 0,679, respectivamente). Conclusão: O tratamento com pressão positiva contínua nas vias aéreas reduziu a dispersão do intervalo QT corrigido em pacientes com apneia obstrutiva do sono grave. Além disso, o encurtamento de dispersão do intervalo QT corrigido em pacientes com apneia obstrutiva do sono grave pode reduzir o risco de arritmias e doenças cardiovasculares.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Long QT Syndrome/prevention & control , Sleep Apnea, Obstructive/therapy , Continuous Positive Airway Pressure/methods , Severity of Illness Index , Long QT Syndrome/etiology , Body Mass Index , Case-Control Studies , Prospective Studies , Longitudinal Studies , Treatment Outcome , Polysomnography , Sleep Apnea, Obstructive/complications , ElectrocardiographyABSTRACT
INTRODUCTION: Severe obstructive sleep apnea is associated with increased QT corrected interval dispersion and continuous positive airway pressure is thought to improve this arrhythmogenic marker. OBJECTIVE: The aim of the study was to determine the decrease of ratio of cardiovascular risk in patients with obstructive sleep apnea. METHODS: The study included 65 patients with severe obstructive sleep apnea who had an apnea-hypopnea index score of >30. Each patient underwent 12-channel electrocardiogram monitoring and polysomnography. Patients with an apnea-hypopnea index score of <5 were used as the control group. The control group also underwent electrocardiogram monitoring and polysomnography testing. The QT corrected interval dispersion levels of both groups were calculated. Three months after continuous positive airway pressure treatment, electrocardiogram recordings were obtained from the 65 patients with severe obstructive sleep apnea again, and their QT corrected interval dispersion values were calculated. RESULTS: There were 44 male and 21 female patients with severe obstructive sleep apnea syndrome. The age, gender, body mass index, initial saturation, minimum saturation, average saturation, and desaturation index were determined in both groups. The QT corrected intervals of the obstructive sleep apnea patients (62.48±16.29ms) were significantly higher (p=0.001) than those of the control group (29.72±6.30ms). There were statistically significant differences between the QT corrected values before and after the continuous positive airway pressure treatment, with pretreatment QT corrected intervals of 62.48±16.29ms and 3-month post-treatment values of 41.42±16.96ms (p=0.001). There was a positive and significant correlation between QT corrected interval dispersion periods and the apnea-hypopnea index and hypopnea index in obstructive sleep apnea patients (p=0.001; r=0.71; p=0.001; r=0.679, respectively). CONCLUSION: Continuous positive airway pressure treatment reduced the QT corrected interval dispersion in patients with severe obstructive sleep apnea. In addition, shortening the QT corrected interval dispersion periods in patients with severe obstructive sleep apnea may reduce their risk of arrhythmias and cardiovascular disease.
Subject(s)
Continuous Positive Airway Pressure/methods , Long QT Syndrome/prevention & control , Sleep Apnea, Obstructive/therapy , Adult , Body Mass Index , Case-Control Studies , Electrocardiography , Female , Humans , Long QT Syndrome/etiology , Longitudinal Studies , Male , Middle Aged , Polysomnography , Prospective Studies , Severity of Illness Index , Sleep Apnea, Obstructive/complications , Treatment OutcomeABSTRACT
The main objective of the present study was to evaluate the reduction in halofantrine (Hf) toxicity, an antimalarial drug frequently associated with QT interval prolongation in electrocardiogram, by its entrapment in poly-epsilon-caprolactone nanocapsules (NC). The acute lethal dose (LD(100)) of Hf.HCl experimentally observed was 200 mg/kg whereas the calculated LD(50) was 154 mg/kg. In contrast, the LD(100) for Hf-NC was 300 mg/kg with a longer mean time to death than Hf.HCl. The calculated LD(50) was 249 mg/kg for Hf-NC. The Hf entrapped in PCL NC presented a greater efficacy than PLA-PEG NC and than Hf solution in P. berghei-infected mice at 1 mg/kg. The cardiovascular parameters, ECG and arterial blood pressure, were evaluated in anaesthetized Wistar rats after the IV administration of a single, especially high dose (100 and 150 mg/kg) of halofantrine base loaded-nanocapsules (Hf-NC) or halofantrine chlorhydrate (Hf.HCl) solution. It was observed that Hf solution caused prolongation of the QT and PR intervals of the ECG; however, this effect was significantly (P<0.001) reduced when Hf was administered entrapped in nanocapsules. The treatment with Hf.HCl induced a pronounced bradycardia and severe hypotension leading to death. The effect of Hf-NC upon heart rate was reduced from 58 to 75% for 100 and 150 mg/kg, respectively, when compared with Hf.HCl solution. These findings show that the encapsulation of halofantrine reduces the QT interval prolongation of ECG in rats and suggest that a modification of drug distribution was possible by using nanocapsules. Hf encapsulation was the main factor responsible for the significant reduction in cardiac toxicity observed.
Subject(s)
Antimalarials/toxicity , Bradycardia/chemically induced , Heart/drug effects , Hypotension/chemically induced , Long QT Syndrome/prevention & control , Nanocapsules , Phenanthrenes/toxicity , Animals , Antimalarials/administration & dosage , Bradycardia/physiopathology , Bradycardia/prevention & control , Disease Models, Animal , Dose-Response Relationship, Drug , Electrocardiography , Hypotension/physiopathology , Hypotension/prevention & control , Lethal Dose 50 , Long QT Syndrome/chemically induced , Malaria/drug therapy , Malaria/parasitology , Male , Mice , Phenanthrenes/administration & dosage , Plasmodium berghei/drug effects , Plasmodium berghei/physiology , Rats , Rats, WistarABSTRACT
Os autores relatam o caso de uma criança de 23 meses de idade, portadora de síndrome do QT longo congênito,submetida a implante de cardioversor-desfibrilador atrioventricular. A criança apresentou três episódios de fibrilação ventricular revertida após manobras convencionais de ressuscitação cardiopulmonar e desfibrilação transtorácica externa, previamente ao implante. Devido a descontinuidade da fabricação de placas epimiocárdicas, foi utilizado a via transtorácica para o implante dos cabos-eletrodos, com abordagem epimiocárdica para o eletrodo atrial e endocárdica transatrial para o implante do eletrodo ventricular convencional
Subject(s)
Humans , Male , Infant , Cardiac Pacing, Artificial , Long QT Syndrome/congenital , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Long QT Syndrome/prevention & control , Atrial Fibrillation/physiopathologyABSTRACT
BACKGROUND: The present study examined pacing site-dependent changes in QT interval and transmural dispersion of repolarization (TDR) and their potential role in the development of torsade de pointes (TdP). METHODS AND RESULTS: In humans, the QT interval, JT interval, and TDR were measured in 29 patients with heart failure during right ventricular endocardial pacing (RVEndoP), biventricular pacing (BiVP), and left ventricular epicardial pacing (LVEpiP). In animal experiments, pacing site--dependent changes in ventricular repolarization were examined with a rabbit left ventricular wedge preparation in which action potentials from endocardium and epicardium could be simultaneously recorded with a transmural ECG. In humans, LVEpiP and BiVP led to significant QT and JT prolongation. LVEpiP also enhanced TDR. Frequent R-on-T extrasystoles generated by BiVP and LVEpiP but completely inhibited by RVEndoP occurred in 4 patients, of whom 1 developed multiple episodes of nonsustained polymorphic ventricular tachycardia and another suffered incessant TdP. In rabbit experiments, switching from endocardial to epicardial pacing produced a net increase in QT interval and TDR by 17+/-5 and 22+/-5 ms, respectively (n=6, P<0.01), without parallel increases in ventricular transmembrane action potential durations. Epicardial pacing facilitated transmural propagation of early afterdepolarization, leading to the development of R-on-T extrasystoles and TdP in the presence of action potential duration-prolonging agents. CONCLUSIONS: LVEpiP and BiVP increase QT, JT, and TDR by altering the transmural sequence of activation of the intrinsically heterogeneous ventricular myocardium. Our data suggest that the resultant exaggeration of arrhythmic substrates can lead to the development of TdP in a subset of patients.