A novel system for mapping regional electrical properties and characterizing arrhythmia in isolated intact rat atria

Abstract

Introduction: Detailed global maps of atrial electrical activity are needed to understand mechanisms of atrial rhythm disturbance in small animal models of heart disease. To date, optical mapping systems have not provided enough spatial resolution across sufficiently extensive regions of intact atrial preparations to achieve this goal. Objectives: To develop an integrated platform for quantifying regional electrical properties and analyzing reentrant arrhythmia in a bi-atrial preparation. Methods: Intact atria from 6/7 months old female spontaneously hypertensive rats (N=6) were isolated and secured in a constant flow superfusion chamber at 37°C. Optical mapping was performed with the membrane-voltage dye di-4 ANEPPS using LED excitation and a sCMOS camera. Programmed stimulus trains were applied from RA and LA sites to assess rate-dependent electrical behavior and to induce atrial arrhythmia. Signal-to-noise ratio was improved by sequential processing steps that included spatial smoothing, temporal filtering and, in stable rhythms, ensemble-averaging. Results: Activation time, repolarization time and action potential duration (APD) maps were constructed at high spatial resolution for a wide range of coupling intervals. These data were highly consistent within and between experiments. They confirmed preferential atrial conduction pathways and demonstrated distinct medial-to-lateral APD gradients. We also showed that reentrant arrhythmias induced in this preparation were explained by the spatial variation of these electrical properties. Conclusion: Our new methodology provides a robust means of 1) quantifying regional electrical properties in the intact rat atria at higher spatio-temporal resolution than previously reported, and 2) characterizing reentrant arrhythmia and analyzing mechanisms that give rise to it.

Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals

“…1 . In terms of species used, the majority of these studies (∼67%) used rodents, with approximately equal distribution between mice ( 23 – 33 ) and rats ( 34 – 42 ). Guinea pig ( 43 – 45 ) and porcine hearts ( 46 – 48 ) were each used in ∼10% of studies, followed by a small number of reports in rabbit ( 49 ), zebrafish ( 50 ), quail ( 51 ), and canine ( 52 ) hearts.…”

“…In terms of disease models, genetically modified mice ( 23 , 26 , 28 – 33 ) or specific rat strains (e.g., spontaneously hypertensive rat) ( 34 , 35 , 40 ) were most commonly assessed (∼37% of studies), and myocardial infarction, ischemia, or hypoxia were evaluated in ∼27% of studies ( 25 , 31 , 35 , 38 , 42 , 44 , 45 , 47 ). Around 16% of investigations used pharmacological modulation ( 24 , 43 , 49 , 50 , 52 ).…”