Journal: bioRxiv

Article Title: Classifying drugs by their arrhythmogenic risk using machine learning

doi: 10.1101/545863

Figure Lengend Snippet: We characterize calcium transients in ventricular cardiomyocytes in response to drugs, both computationally (top) and experimentally (bottom) and identify the ion channels that most likely generate early afterdepolarizations (left). We then screen the concentration space of the two most relevant channels and identify the classification boundary between the arrhythmic and non-arrhythmic domains using high performance computing and machine learning (center). We validate our approach using electrocardiograms, both computationally and experimentally, in whole heart simulations and isolated Langendorff perfused hearts (right). We demonstrate the potential of our new classifier by risk stratifying 23 common drugs and comparing the result against the reported risk categories of these compounds.

Article Snippet: We excised the hearts from anesthetized rats (2.5% isoflurane in 95% oxygen and 5% carbon dioxide), immediately cannulated the aorta, connected it to a constant pressure perfusion Langendorff system (Harvard Apparatus, Massachusetts) with Krebs solution (118mM NaCl, 4.75mM KCl, 25mM NaHCO 3 , 1.2mM KH 2 PO 4 , 1.2mM MgSO 4 , 1.5mM CaCl 2 , 11mM glucose, and 2mM Pyruvate), warmed to 37° C, and bubbled with 95% oxygen and 5% carbon dioxide.

Techniques: Concentration Assay, Isolation

Journal: Indian Journal of Pharmaceutical Sciences

Article Title: Mechanism(s) Involved in Carbon Monoxide-releasing Molecule-2-mediated Cardioprotection During Ischaemia-reperfusion Injury in Isolated Rat Heart

doi: 10.4103/0250-474X.107047

Figure Lengend Snippet: Experimental design for CORM-2-mediated cardioprotection and role of various kinases. The isolated, Langendorff-perfused rat hearts were stabilised for 10 min, perfused for 15 min with K–H buffer. Hearts were treated with Vehicle or iCORM-2 (inactive form of CORM) or CORM-2 (50 μM) (a, b and c). The treatment with various inhibitors like SCIO-469 (1 μM) or SB-203580 (10 μM) or chelerythrine (10 μM) or wortmannin (100 nM) was initiated 5 min before CORM-2 administration and continued during CORM-2 treatment followed by 30 min of global ischaemia and 120 min of reperfusion (d, e and f). Some hearts (g, h and i) pretreated with CORM-2 and 100 nM wortmannin, the treatment with wortmannin was initiated 5 min before CORM-2 administration and continued during CORM-2 treatment and throughout reperfusion.

Article Snippet: Isolated heart was cannulated via aorta and perfused in the Langendorff's mode at constant perfusion pressure 70 mmHg using Radnoti Langendorff constant pressure non-recirculating system (Radnoti glass technology Inc., CA, USA).

Techniques: Isolation