title: Enhanced dispersion of repolarization explains increased arrhythmogenesis in severe versus therapeutic hypothermia.
abstract: BACKGROUND
  Hypothermia is proarrhythmic, and, as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiological effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling versus rewarming would alter hypothermia-induced arrhythmia substrates.
  
  
  RESULTS
  Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling and during rewarming. Electrophysiological parameters were examined while varying the depth of hypothermia. On cooling to 26°C, DOR increased from 26±4 ms to 93±18 ms (P=0.021); conduction velocity decreased from 35±5 cm/s to 22±5 cm/s (P=0.010). On rewarming to 36°C, DOR remained prolonged, whereas conduction velocity returned to baseline. Conduction block and reentry was observed in all severe hypothermia preparations. Ventricular fibrillation/ventricular tachycardia was seen more during rewarming (4/5) versus cooling (2/6). In TH (n=7), cooling to 32°C mildly increased DOR (31±6 to 50±9, P=0.012), with return to baseline on rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis.
  
  
  CONCLUSIONS
  Hypothermia amplifies DOR and is a mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH and has implications for protocols for the clinical application of TH.
authors.affiliation: The Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH, USA. jpiktel@metrohealth.org
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Piktel
authors.forename: Darwin
authors.initials: D
authors.lastname: Jeyaraj
authors.forename: Tamer H
authors.initials: TH
authors.lastname: Said
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenbaum
authors.forename: Lance D
authors.initials: LD
authors.lastname: Wilson
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology*; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology*; D007035:Hypothermia / Q000150:complications* / Q000503:physiopathology*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D015994:Incidence; D023421:Models, Animal; D012307:Risk Factors; D012720:Severity of Illness Index; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D013696:Temperature; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology