Translate this page to:
Arabic
In JoVE (1)
Other Publications (4)
Automatic Translation
This translation into Arabic was automatically generated.
English Version | Other Languages
Articles by Mark D. McCauley in JoVE
JoVE General
الإسعافية ECG التسجيل في الفئران
1Department of Molecular Physiology and Biophysics, Baylor College of Medicine (BCM), 2The Margaret M. and Albert B. Alkek Department of Medicine, Baylor College of Medicine (BCM)
وقد برزت القياس عن بعد ECG بوصفه أداة أساسية في تقييم النماذج الحيوانية لعدم انتظام ضربات القلب والموت المفاجئ بسبب أمراض القلب. هنا ، فإننا نقدم دليلا متدرج للتسجيلات ECG القياس عن بعد للتطبيق في المدى الطويل مراقبة تخطيط القلب المتنقلة في الفئران.
Other articles by Mark D. McCauley on PubMed
Animal Models of Arrhythmogenic Cardiomyopathy
Arrhythmogenic cardiomyopathies are a heterogeneous group of pathological conditions that give rise to myocardial dysfunction with an increased risk for atrial or ventricular arrhythmias. Inherited defects in cardiomyocyte proteins in the sarcomeric contractile apparatus, the cytoskeleton and desmosomal cell-cell contact junctions are becoming recognized increasingly as major causes of sudden cardiac death in the general population. Animal models have been developed for the systematic dissection of the genetic pathways involved in the pathogenesis of arrhythmogenic cardiomyopathies. This review presents an overview of current animal models for arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) associated with cardiac arrhythmias and sudden cardiac death.
Ryanodine Receptor Phosphorylation by Calcium/calmodulin-dependent Protein Kinase II Promotes Life-threatening Ventricular Arrhythmias in Mice with Heart Failure
approximately half of patients with heart failure die suddenly as a result of ventricular arrhythmias. Although abnormal Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca(2+) remain unknown. We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias.
Targeting Ryanodine Receptors for Anti-arrhythmic Therapy
Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca(2+)) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca(2+) release has been linked to arrhythmogenesis in both the inherited arrhythmia syndrome 'catecholaminergic polymorphic ventricular tachycardia' and acquired forms of heart disease (eg, atrial fibrillation, heart failure). Several classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca(2+) leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.
Pathogenesis of Lethal Cardiac Arrhythmias in Mecp2 Mutant Mice: Implication for Therapy in Rett Syndrome
Rett syndrome is a neurodevelopmental disorder typically caused by mutations in methyl-CpG-binding protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), an indication of a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm. Male mice lacking MeCP2 function, Mecp2(Null/Y), also have prolonged QTc and show increased susceptibility to induced ventricular tachycardia. Female heterozygous null mice, Mecp2(Null/+), show an age-dependent prolongation of QTc associated with ventricular tachycardia and cardiac-related death. Genetic deletion of MeCP2 function in only the nervous system was sufficient to cause long QTc and ventricular tachycardia, implicating neuronally mediated changes to cardiac electrical conduction as a potential cause of ventricular tachycardia in Rett syndrome. The standard therapy for prolonged QTc in Rett syndrome, β-adrenergic receptor blockers, did not prevent ventricular tachycardia in Mecp2(Null/Y) mice. To determine whether an alternative therapy would be more appropriate, we characterized cardiomyocytes from Mecp2(Null/Y) mice and found increased persistent sodium current, which was normalized when cells were treated with the sodium channel-blocking anti-seizure drug phenytoin. Treatment with phenytoin reduced both QTc and sustained ventricular tachycardia in Mecp2(Null/Y) mice. These results demonstrate that cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control, which leads to increased persistent sodium current. Our findings suggest that treatment in people with Rett syndrome would be more effective if it targeted the increased persistent sodium current to prevent lethal cardiac arrhythmias.
