Resistance to ventricular fibrillation predicted by the QRS/QTc - Ratio in an intact rat model of hypothermia/rewarming (original) (raw)
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Europace, 2014
Hypothermia is well known to be pro-arrhythmic, yet it has beneficial effects as a resuscitation therapy and valuable during intracardiac surgeries. Therefore, we aim to study the mechanisms that induce fibrillation during hypothermia. A better understanding of the complex spatiotemporal dynamics of heart tissue as a function of temperature will be useful in managing the benefits and risks of hypothermia.
Journal of Translational Medicine, 2015
Introduction: Mild therapeutic hypothermia (MTH) is being used after cardiac arrest for its expected improvement in neurological outcome. Safety of MTH concerning inducibility of malignant arrhythmias has not been satisfactorily demonstrated. This study compares inducibility of ventricular fibrillation (VF) before and after induction of MTH in a whole body swine model and evaluates possible interaction with changing potassium plasma levels. Methods: The extracorporeal cooling was introduced in fully anesthetized swine (n = 6) to provide MTH. Inducibility of VF was studied by programmed ventricular stimulation three times in each animal under the following: during normothermia (NT), after reaching the core temperature of 32°C (HT) and after another 60 minutes of stable hypothermia (HT60). Inducibility of VF, effective refractory period of the ventricles (ERP), QTc interval and potassium plasma levels were measured. Results: Starting at normothermia of 38.7 (IQR 38.2; 39.8)°C, HT was achieved within 54 (39; 59) minutes and the core temperature was further maintained constant. Overall, the inducibility of VF was 100% (18/18 attempts) at NT, 83% (15/18) after reaching HT (P = 0.23) and 39% (7/18) at HT60 (P = 0.0001) using the same protocol. Similarly, ERP prolonged from 140 (130; 150) ms at NT to 206 (190; 220) ms when reaching HT (P < 0.001) and remained 206 (193; 220) ms at HT60. QTc interval was inversely proportional to the core temperature and extended from 376 (362; 395) at NT to 570 (545; 599) ms at HT. Potassium plasma level changed spontaneously: decreased during cooling from 4.1 (3.9; 4.8) to 3.7 (3.4; 4.1) mmol/L at HT (P < 0.01), then began to increase and returned to baseline level at HT60 (4.6 (4.4; 5.0) mmol/L, P = NS). Conclusions: According to our swine model, MTH does not increase the risk of VF induction by ventricular pacing in healthy hearts. Moreover, when combined with normokalemia, MTH exerts an antiarrhythmic effect despite prolonged QTc interval.
Relationships of the Cardiac Signal and Heat Acclimated State: Spectral Profiles from ECG Analysis
ECG signal has been analyzed to assess the state of heat acclimation in rats. Adult rats, were divided into control and acclimation groups. The ECG signals were obtained from the telemetry transmitters implanted into the rats. The power spectral density of unit time-differenced ECG series was computed. The spectral profiles for the acclimated rats show significantly smoother profiles following heat acclimation compared to the same for the control rats. The progression of acclknation also can n^rS^T ? e statlstlcal comparison against the acclimated spectral pattern. The Mann-Whitney rank sum statistic (MWRS) between the average energy spectral profile and the spectral profile for individual days shows that subsequent to acclimation the MWRS usually drops to low values (usually <1), whereas it remains >1 and usually >1 96 for the control group. The differential profiles derived by subtracting the bi-directionally low-pass filtered profile from the original spectral profile show distinctly reduced variations for the heat acclimated rats compared to the control rats 14. SUBJECT TERMS Heart rate variability, heat acclimation, ECG, rats 17. SECURITY CLASSIFICATION
Circulation Journal, 2009
Background: Therapeutic hypothermia (TH, 30°C) protects the brain from hypoxic injury. However, TH may potentiate the occurrence of lethal ventricular fibrillation (VF), although the mechanism remains unclear. The present study explored the hypothesis that TH enhances wavebreaks during VF and S1 pacing, facilitates pacinginduced spatially discordant alternans (SDA), and increases the vulnerability of pacing-induced VF. Methods and Results: Using an optical mapping system, epicardial activations of VF were studied in 7 Langendorff-perfused isolated rabbit hearts at baseline (37°C), TH (30°C), and rewarming (37°C). Action potential duration (APD)/conduction velocity (CV) restitution and APD alternans (n=6 hearts) were determined by S1 pacing at these 3 stages. During TH, there was a higher percentage of VF duration containing epicardial repetitive activities (spatiotemporal periodicity) (P<0.001). However, TH increased phase singularity number (wavebreaks) during VF (P<0.05) and S1 pacing (P<0.05). TH resulted in earlier onset of APD alternans (P<0.001), which was predominantly SDA (P<0.05), and increased pacing-induced VF episodes (P<0.05). TH also decreased CV, shortened wavelength, and enhanced APD dispersion and the spatial heterogeneity of CV restitution. Conclusions: TH (30°C) increased the vulnerability of pacing-induced VF by (1) facilitating wavebreaks during VF and S1 pacing, and (2) enhancing proarrhythmic electrophysiological parameters, including promoting earlier onset of APD alternans (predominantly SDA) during S1 pacing.
Arrhythmogenicity of hypothermia - a large animal model of hypothermia
2014
Ten sheep underwent systemic hypothermia using a venous-venous extra-corporeal circuit whilst instrumented with a 12 lead ECG. An epicardial sock recorded potentials to 30 8C (N = 10) or 26 8C (N = 6). Activation times (AT) and Activation Recovery Intervals (ARI) were calculated using custom software.
In Vitro Arrhythmia Generation by Mild Hypothermia-a Pitchfork Bifurcation Type Process
The neurological damage after cardiac arrest (CA) constitutes a big challenge of hospital discharge. The therapeutic hypothermia (34 • C − 32 • C) has shown its benefit to reduce cerebral oxygen demand and improve neurological outcomes after the cardiac arrest. However, it can have many adverse effects, among them the cardiac arrhythmia generation represents an important part (up to 34%, according different clinical studies). Monolayer cardiac culture is prepared with cardiomyocytes from newborn rat directly on the multi-electrodes array, which allows acquiring the extracellular potential of the culture. The temperature range is 37 • C − 30 • C − 37 • C, representing the cooling and rewarming process in the therapeutic hypothermia. Experiments showed that at 35 • C, the acquired signals are characterized by period-doubling phenomenon, compared to signals at other temperatures. Spiral waves, commonly considered as a sign of cardiac arrhythmia, are observed in the reconstructed activation map. With an approach from nonlinear dynamics, phase space reconstruction, it is shown that at 35 • C, the trajectories of these signals formed a spatial bifurcation, even trifurcation. Another transit point is found between 30 • C − 33 • C, which agreed with other clinical studies that induced hypothermia after cardiac arrest should not be below 32 • C. The process of therapeutic hypothermia after cardiac arrest can be represented by a Pitchfork bifurcation type process, which could explain the different ratio of arrhythmia among the adverse effects after this therapy. This nonlinear dynamics suggests that a variable speed of cooling / rewarming, especially when passing 35 • C, would help to decrease the ratio of post-hypothermia arrhythmia and then improve the hospital output.
Cardiac arrhythmia induced by hypothermia in a cardiac model in vitro
Journal of Electrocardiology, 2013
Patients that have survived Out-of-Hospital Cardiac Arrest usually develop some degree of neurological problems. A common treatment to mitigate neurological damage is mild therapeutic hypothermia (MTH). However, MTH has adverse effects, including arrhythmia. In order to explore the mechanisms of arrhythmia linked to MTH, we took measures on a temperature controlled experimental model which simulates MTH. These measures consisted of extracellular potential of cardiac culture on a multi-electrode array and we analysed them in terms of nonlinear dynamics. The results showed that cardiac arrhythmia is induced around temperature 35°C (spiral waves at T~35°C against plane waves at other temperatures). A period-doubling phenomenon is also observed around T=35°C, confirmed with the analysis methods. All results showed that 35°C is a critical temperature triggering arrhythmia. This suggests that the re-warming / cooling speed could affect the arrhythmia generation after MTH.
The therapeutic hypothermia (under 34˝C´32˝C during 12´24h) can help reduce cerebral oxygen demand and improve neurological outcomes after the cardiac arrest. However it can have many adverse effects. The cardiac arrhythmia generation represents an important part among these adverse effects. In order to study the arrhythmia generation after therapeutic hypothermia, an experimental cardiomyocytes model is used. The experiments showed that at 35˝C, the acquired extracellular potential of the culture are characterized by period-doubling phenomenon. Spiral waves are observed as well in this case. The results suggested that the global dynamics of therapeutic hypothermia after cardiac arrest can be represented by a Pitchfork bifurcation, which could explain the different ratio of arrhythmia among the adverse effects after this therapy. A variable speed of cooling / rewarming, especially when passing 35˝C, would help reduce the post-hypothermia arrhythmia.
2011
The following articles are being highlighted as part of Circulation: Arrhythmia and Electrophysiology’s Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in Circulation: Arrhythmia and Electrophysiology and the rest of the Circulation portfolio. The studies included in this article represent the most read manuscripts published on the topic of atrial fibrillation in 2009 and 2010. (Circ Arrhythm Electrophysiol. 2011;4:e76-e83.)