In vivo ratiometric optical mapping enables high-resolution cardiac electrophysiology in pig models

Autor: José Manuel Alfonso-Almazán, Nicasio Pérez-Castellano, Jorge G. Quintanilla, Ping Yan, Carlos Galán-Arriola, Julián Pérez-Villacastín, Peter D. Lee, David Filgueiras-Rama, Leslie M. Loew, Javier Sánchez-González, Borja Ibanez
Přispěvatelé: Ministerio de Ciencia, Innovación y Universidades (España), Fundación ProCNIC, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Unión Europea. Comisión Europea, Fundación Interhospitalaria de Investigación Cardiovascular, Sociedad Española de Cardiología, National Institutes of Health (Estados Unidos)
Rok vydání: 2019
Předmět:
Novel Methodology
Time Factors
Optical mapping
Materials science
Swine
Physiology
Sus scrofa
Action Potentials
030204 cardiovascular system & hematology
Nerve conduction velocity
03 medical and health sciences
0302 clinical medicine
Heart Rate
Predictive Value of Tests
In vivo
Physiology (medical)
medicine
Animals
Cardiac fibrillation
Voltage-sensitive dyes
Fluorescent Dyes
030304 developmental biology
0303 health sciences
Cardiac electrophysiology
Editorials
Reproducibility of Results
Isolated Heart Preparation
Original Articles
medicine.disease
Voltage-Sensitive Dye Imaging
Cardiotoxicity
Disease Models
Animal
Electrophysiology
Ventricular Fibrillation
In vivo imaging
Ventricular fibrillation
Electrophysiologic Techniques
Cardiac
Cardiology and Cardiovascular Medicine
Preclinical imaging
Ex vivo
Biomedical engineering
Zdroj: Cardiovascular Research
Repisalud
Instituto de Salud Carlos III (ISCIII)
Cardiovasc Res
ISSN: 1755-3245
0008-6363
DOI: 10.1093/cvr/cvz039
Popis: Aims Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. Methods and results First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63–138) cm/s vs. 51 (41–64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217–254) ms vs. 192 (182–233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min−1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA. Conclusions In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models.
Graphical Abstract Graphical Abstract
Databáze: OpenAIRE
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