Cardiomyocyte Responses to Thermal Excursions: Implications for Electrophysiological Cardiac Mapping

Abstract

Cryotherapy is emerging as a treatment method to identify and ablate atrial and ventricular tachyarrhythmias. Cryotherapy utilizes reversible moderate ultra-hypothermic temperatures to transiently halt electrophysiological activity to identify target areas for ablation with minimal damage to the nonarrhythmogenic tissue. This represents a potential advantage over heat-based therapies. Subsequent application of subfreezing temperatures to the targeted cells results in cellular ablation and ultimately correction of the arrhythmia. An in vitro study was performed to characterize and investigate the efficacy of cryotherapy procedures in mammalian cardiac systems. Mammalian cardiomyocytes were isolated from neonatal rats and seeded in tissue culture plates. Samples experienced brief (15 sec to 60 sec) thermal excursions of temperatures ranging from 60°C to −20°C. Upon return to normal culture conditions (37°C), cellular metabolic activity and contractile response were monitored for 72 h and compared to controls. The cryomapping temperature range (37°C to 0°C) displayed similar metabolic rates (100%) and spontaneous cardiomyocyte contractions following return to normothermic conditions. Video monitoring of cardiomyocytes cooled to 0.5°C for 20 min demonstrated retention of spontaneous contractile properties following rewarming. Application of ablative temperatures (−2°C to −12°C) resulted in a decrease in metabolic activity of >20% compared to controls and loss of spontaneous contractions. Metabolic activity in cells treated at temperatures colder than −13°C was reduced by 95%, indicative of total cellular ablation. Metabolic activity in heat-treated cells (>50°C) was also reduced to 95% of control levels and exhibited no beating activity. Comparison of exposures of 15 sec to 60 sec at the various temperatures revealed no significant differences in either viability or functional assessments. Cryomapping displays a greater thermal range of reversibility compared to heat, suggesting cryotherapy may be a more manageable alternative for mapping procedures. In addition, cryotherapy also displays effective ablative capacity in myocardial systems.