Frequency-dependent electrophysiological properties of concealed slow pathway of isolated rabbit atrioventricular node preparation after fast pathway ablation in a functional model

Introduction: Intranodal pathways of atrioventricular (AV) node play a vital role in the delay of conduction time in response to various atrial inputs. The present study was aimed to determine the frequency-dependent electrophysiological properties of concealed slow pathway according to a functional model of isolated rabbit atrioventricular node preparation after fast pathway ablation. Methods: Experiments were carried out in rabbit isolated heart AV-nodal preparations (N=8) by superfused/perfused mode. Extracellular recording was carried out from transitional cells of posterior and anterior extension of AV-node and upper part of atrium and its bundle. Unipolar silver electrode (100 μm) and direct voltage (100-110 V) was applied to create AV-nodal fast pathway ablation. Results: Minimum conduction time (AHmin) was significantly increased after fast pathway ablation (p<0.05). Fast pathway ablation had no significant impact on fatigue phenomenon but significantly reduced facilitation value (p<0.05). Rate-dependency properties of concealed slow pathway were explained according to functional nodal model. Conclusion: The mathematical functional model accurately simulated frequency-dependent electrophysiological properties of concealed slow pathway after fast pathway ablation, but some modifications are necessary for accurate prediction of nodal behavior in various cycle lengths and in arrhythmia. Concealed slow pathway may be considered as a potential electrophysiological substrate of fatigue and facilitation phenomenon

Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart

Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats� hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria. © 2020 Elsevier B.V