Flow Augmentation in the Myocardium by Ultrasound Cavitation of Microbubbles: Role of Shear-Mediated Purinergic Signaling.

Background: Ultrasound-mediated cavitation of microbubble contrast agents produces high intravascular shear. We hypothesized that microbubble cavitation increases myocardial microvascular perfusion through shear-dependent purinergic pathways downstream from ATP release that is immediate and sustained through cellular ATP channels such as Pannexin-1.

Methods: Quantitative myocardial contrast echocardiography perfusion imaging and in vivo optical imaging of ATP was performed in wild-type and Pannexin-1-deficient (Panx1) mice before and 5 and 30 minutes after 10 minutes of ultrasound-mediated (1.

Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington's disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans.

Pathogenic troponin T mutants with opposing effects on myofilament Ca sensitivity attenuate cardiomyopathy phenotypes in mice.

Mutations in cardiac troponin T (TnT) associated with hypertrophic cardiomyopathy generally lead to an increase in the Ca sensitivity of contraction and susceptibility to arrhythmias. In contrast, TnT mutations linked to dilated cardiomyopathy decrease the Ca sensitivity of contraction. Here we tested the hypothesis that two TnT disease mutations with opposite effects on myofilament Ca sensitivity can attenuate each other's phenotype.

Mitochondrial-Mediated Oxidative Ca/Calmodulin-Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study.

Background Oxidative stress-mediated Ca/calmodulin-dependent protein kinase II (Ca MKII) phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial-derived reactive oxygen species (md ROS ) and increased Ca MKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally. Methods and Results We hypothesize that pathological md ROS can cause erratic action potentials through the oxidation-dependent Ca MKII activation pathway.

Pannexin Channel Inhibition: An Evolving Target to Lower Blood Pressure?

More than 50 years after spironolactone has come on the market its mechanism of action continues to expand. In this issue of , Good document the discovery that spironolactone is not only an inhibitor of the mineralocorticoid receptor, but also inhibits pannexin 1 channels.