Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model (original) (raw)
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Hypokalemia during the cooling phase of therapeutic hypothermia and its impact on arrhythmogenesis
Resuscitation, 2010
Background: Mild to moderate therapeutic hypothermia (TH) has been shown to improve survival and neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) as the presenting rhythm. This approach entails the management of physiological variables which fall outside the realm of conventional critical cardiac care. Management of serum potassium fluxes remains pivotal in the avoidance of lethal ventricular arrhythmia. Methods: We retrospectively analyzed potassium variability with TH and performed correlative analysis of QT intervals and the incidence of ventricular arrhythmia. Results: We enrolled 94 sequential patients with OHCA, and serum potassium was followed intensively. The average initial potassium value was 3.9 ± 0.7 mmol l −1 and decreased to a nadir of 3.2 ± 0.7 mmol l −1 at 10 h after initiation of cooling (p < 0.001). Eleven patients developed sustained polymorphic ventricular tachycardia (PVT) with eight of these occurring during the cooling phase. The corrected QT interval prolonged in relation to the development of hypothermia (p < 0.001). Hypokalemia was significantly associated with the development of PVT (p = 0.002), with this arrhythmia being most likely to develop in patients with serum potassium values of less than 2.5 mmol l −1 (p = 0.002). Rebound hyperkalemia did not reach concerning levels (maximum 4.26 ± 0.8 mmol l −1 at 40 h) and was not associated with the occurrence of ventricular arrhythmia. Furthermore, repletion of serum potassium did not correlate with the development of ventricular arrhythmia. Conclusions: Therapeutic hypothermia is associated with a significant decline in serum potassium during cooling. Hypothermic core temperatures do not appear to protect against ventricular arrhythmia in the context of severe hypokalemia and cautious supplementation to maintain potassium at 3.0 mmol l −1 appears to be both safe and effective.
Acta Physiologica, 2010
Aim: The induction of mild hypothermia (MH; 33°C) has become the guideline therapy to attenuate hypoxic brain injury after out-of-hospital cardiopulmonary resuscitation. While MH exerts a positive inotropic effect in vitro, MH reduces cardiac output in vivo and is thus discussed critically when severe cardiac dysfunction is present in patients. We thus assessed the effect of MH on the function of the normal heart in an in vivo model closely mimicking the clinical setting. Methods: Ten anaesthetized, female human-sized pigs were acutely catheterized for measurement of pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz catheter) and for vena cava inferior occlusion. Controlled MH (from 37 to 33°C) was induced by a vena cava inferior cooling catheter. Results: With MH, heart rate (HR) and whole body oxygen consumption decreased, while lactate levels remained normal. Cardiac output, left ventricular (LV) volumes, peak systolic and end-diastolic pressure and dP/dt max did not change significantly. Changes in dP/dt min and the time constant of isovolumetric relaxation demonstrated impaired active relaxation. In addition, MH prolonged the systolic and shortened the diastolic time interval. Pressure-volume analysis revealed increased end-systolic and end-diastolic stiffness, indicating positive inotropy and reduced end-diastolic distensibility. Positive inotropy was preserved during pacing, while LV end-diastolic pressure increased and diastolic filling was substantially impaired due to delayed LV relaxation. Conclusion: MH negatively affects diastolic function, which, however, is compensated for by decreased spontaneous HR. Positive inotropy and a decrease in whole body oxygen consumption warrant further studies addressing the potential benefit of MH on the acutely failing heart.
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.
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.
Critical Care Medicine, 2012
udden death resulting from cardiac arrest (CA) is a leading cause of death in the United States, Canada, and Europe (1-3). It accounts for as many as 50% of deaths in patients with heart disease (4). Despite efforts to improve outcomes from CA, the overall survival rate remains dismal (5, 6). Although the initial success of cardiopulmonary resuscitation (CPR) is approximately 39%, the majority of victims die within 72 hrs of hospital admission (7, 8). Patients successfully resuscitated after CA often present with what is now termed "postresuscitation disease" (9). Severe postresuscitation heart contractile failure has been implicated as one of the most important mechanisms causing these fatal outcomes (10, 11). Indeed, it is brain cellular injury after cerebral ischemia and after reperfusion that accounts for as many as 60% of disabilities in the small number of patients resuscitated after CA that survive to hospital discharge (12, 13). The greatest postresuscitation emphasis has therefore been on minimizing myocardial dysfunction together with the aim to preserve neurologic function (14). Among all postresuscitation care interventions suggested and/or recommended as providing the most persuasive benefits both for the brain and the heart is the use of therapeutic hypothermia (TH) (15-17). When the body temperature is reduced to 32-34°C, which is initiated during CPR or immediately after resuscitation, neurologic outcomes are significantly improved (18-21). The postresuscitation period is marked by hemodynamic instability and Objective: Therapeutic hypothermia initiated with cardiopulmonary resuscitation improves neurologic outcomes and survival after prolonged cardiac arrest. However, the potential mechanism by which hypothermia improves neurologic outcomes remains unclear. In the current study, we investigated the effect of rapid head cooling on 96-hr neurologic outcomes and survival by heart rate variability analysis in a pig model of prolonged cardiac arrest. Design: Prospective randomized controlled animal study. Setting: University-affiliated research laboratory. Subjects: Yorkshire-X domestic pigs (Sus scrofa). Interventions: A protocol of 10 mins of untreated ventricular fibrillation followed by 5 mins of cardiopulmonary resuscitation in a pig model of cardiac arrest was used in this study. Sixteen male domestic pigs weighing between 39 and 45 kg were randomized into two groups, hypothermia (n ؍ 8) and control (n ؍ 8). For the hypothermia group, intranasal-induced head cooling was initiated with cardiopulmonary resuscitation and persisted for 4 hrs after resuscitation. For the control group, cardiopulmonary resuscitation was started with normothermia. Measurements and Main Results: Time and frequency domain heart rate variability was calculated in 5-min sections of electrocardiographic recordings at baseline and 4 hrs after resuscitation. Neurologic outcomes were evaluated every 24 hrs during the 96-hr postresuscitation observation period. No differences in the baseline measurement and resuscitation outcome were observed between the groups. However, the 96-hr cerebral performance categories of the hypothermic group were significantly lower than control (1.0 ؎ 0.0 vs. 4.0 ؎ 1.9, p ؍ .003). Four hrs after resuscitation, mean RR interval, heart rate variability triangular index, and normalized verylow-frequency power were restored to baseline in the hypothermia group. Square root of the mean squared differences of successive RR intervals and SD of instantaneous RR intervals were significantly improved in the cooled animals compared with controls. A significant correlation between 4-hr heart rate variability and 96-hr cerebral performance category was observed in this study. Conclusion: Selective head cooling maintains a certain level of autonomic nervous system function in this pig model of cardiac arrest. The preserved heart rate variability during postresuscitation hypothermia was associated with favorable 96-hr neurologic recovery and survival.
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.
Performance of pig heart after 30 or 120 minutes hypothermic arrest
Journal of Surgical Research, 1983
The effect of the duration of hypothermic (T = 1S'C) potassium cardioplegic arrest and &hernia on the heart was determined by measuring the response of the isolated in situ pig heart to 180 min of perfusion (n = 12) to provide appropriate control values for the study of 30 (n = 25) or 120 (n = 27) min of ischemia, followed by 60 min of reperfusion. In some of these animals, myocardial tissue samples were obtained for measurement of adenosine triphosphate (ATP) and creatine phosphate (CP), (6 in the perfusion group, 7 in the 30 min of ischemia and 60 min of reperfusion group and 15 in the I20 min of ischemia and 60 min of reperfusion group). In the remaining animals, measurements of either left ventricular performance (LVP), myocardial oxygen metabolism (MVOs) or plasma creatine kinase (CK) were obtained (6 in the prolonged perfusion group, 12 in the 120 min of &hernia and 60 min of reperfusion group, [6 LVP and MVO, and 6 CK] and 18 in the 30 min of &hernia and 60 min of reperfusion group [ 13 LVP, 17 MVO, and 6 CK]). During prolonged perfusion, left ventricular performance, expressed as developed pressure, AZ', fell from an initial value of 175 + 36 to 128 + 19 mm Hg at 30 min of perfusion, followed by a more gradual decline to a final value of 113 rt 8 mm Hg at 180 min of perfusion. These decreases were not significantly lower than the initial value. The percentage of myocardial extraction declined in a similar manner, but coronary blood flow was constant over this interval. The primary effect of 30 or 120 min of ischemia was to reduce left ventricular developed pressure, AP, during reperfusion to more than 70% of the corresponding value in the control group (these differences were statistically significant) which suggests that prolonging the period of &hernia did not cauSe further deterioration of cardiac performance. The plasma concentration of CK rose in the control group of hearts subjected to prolonged perfusion from an initial value of 35 + 6 to a final value of 59 k 8 IU/liter (P < 0.05). While plasma CK increased during reperfusion in both &hernia/ reperfusion groups, these values were not significantly higher from prearrest values. Thus hypothermic cardioplegic &hernia of this duration did not appear to result in tissue necrosis, but there was a significant reduction in left ventricular performance which was independent of the duration of &hernia between the limits of 30 and 120 min.
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.
Left ventricular dysfunction following rewarming from experimental hypothermia
Journal of applied physiology (Bethesda, Md. : 1985), 1998
This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25 degreesC and returned to 37 degreesC over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/dtmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (tau) and the LV wall stiffness constant (Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25 degreesC: dP/dtmax 2,180 +/- 158 vs. 760 +/- 78 mmHg/s, SS% 20.1 +/- 1.2 vs. 13.3 +/- 1.0%, SV 11.7 +/- 0.7 vs. 8.5 +/- 0.7 ml, PRSW 90.5 +/- 7.7 vs. 29.1 +/- 5.9 J/m. 10(-2), ...