Abstract
Ventricular arrhythmia induced by ischemia/reperfusion (I/R) injury is a clinical problem in reperfusion therapies for acute myocardial infarction. Ca2+ overload through reactive oxygen species (ROS) production is a major cause for I/R-induced arrhythmia. We previously demonstrated that canstatin, a C-terminal fragment of type IV collagen α2 chain, regulated Ca2+ handling in rat heart. In this study, we aimed to clarify the effects of canstatin on I/R-induced ventricular arrhythmia in rats. Male Wistar rats were subjected to I/R injury by ligating the left anterior descending artery followed by reperfusion. Ventricular arrhythmia (ventricular tachycardia and ventricular fibrillation) was recorded by electrocardiogram. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity and ROS production in neonatal rat cardiomyocytes (NRCMs) stimulated with oxygen glucose deprivation/reperfusion (OGD/R) were measured by lucigenin assay and 2′,7′-dichlorodihydrofluorescein diacetate staining, respectively. The H2O2-induced intracellular Ca2+ ([Ca2+]i) rise in NRCMs was measured by a fluorescent Ca2+ indicator. Canstatin (20 µg/kg) inhibited I/R-induced ventricular arrhythmia in rats. Canstatin (250 ng/mL) inhibited OGD/R-induced NOX activation and ROS production and suppressed the H2O2-induced [Ca2+]i rise in NRCMs. We for the first time demonstrated that canstatin exerts a preventive effect against I/R-induced ventricular arrhythmia, perhaps in part through the suppression of ROS production and the subsequent [Ca2+]i rise.
Highlights
Myocardial infarction (MI) is caused by a coronary thrombosis mainly due to the disruption of atherosclerotic plaque [1]
Ca we investigated the effects of canstatin on I/R-induced ventricular arrhythmia using an in investigated of canstatin on I/R-induced ventricular arrhythmia using in vivo vivo modelthe of effects
]i rise in cardiomyocytes to ventricular arrhythmias [16]
Summary
Myocardial infarction (MI) is caused by a coronary thrombosis mainly due to the disruption of atherosclerotic plaque [1]. Reperfusion therapies, such as percutaneous coronary intervention and thrombolytic therapy, are established as the most effective therapies for acute MI (AMI) [2]. Ischemia/reperfusion (I/R) injury, a critical complication of the therapies, is a serious clinical problem associated with a high mortality [3,4]. More than 80% of AMI patients develop arrhythmia, including lethal ventricular tachycardia (VT) and ventricular fibrillation (VF), during the first 48 h after reperfusion [4]. There is no effective strategy for preventing I/R injury and subsequent arrhythmia [2].
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