Is the combination therapy of IKr-channel blocker and left stellate ganglion block effective for intractable ventricular arrhythmia in a cardiopulmonary arrest patient?

Background: We have previously reported that the defibrillation success rate of intravenous nifekalant hydrochloride (NIF), a pure IKr-channel (IKr: the rapid components of the delayed rectifier potassium current) blocker, was more than 75% for lidocaine-resistant ventricular tachycardia and fibrillation (VT/VF) in patients with out-of-hospital cardiopulmonary arrest (CPA). However, there was no effective treatment for the remaining 25% of patients in whom defibrillation was unsuccessful. We hypothesised that the combination therapy of NIF and left stellate ganglion block (LSGB) was useful for defibrillation in NIF-resistant VT/VF and investigated its efficacy in a retrospective study. Methods and results: We investigated sequentially 272 out-of-hospital CPA patients treated at Tokai University between April and December 2006. VT/VF occurred in 55 patients on arrival or during cardiopulmonary resuscitation (CPR). On the basis of our CPR algorithm, NIF was administered (0.15-0.3 mg/kg, i.v.) after the first direct-current cardioversion. NIF-resistant VT/VFs were observed in 15 out of 55 patients and LSGB was performed on 11 of these with administration of NIF. Sinus rhythm was restored in 7 patients following LSGB (64%) and complete recovery was achieved in 2 patients. In the non-LSGB group, however, all the patients died. Conclusions: The combination therapy of intravenous NIF and LSGB was useful for defibrillation in intractable VT/VF. It is a potential and innovative treatment strategy for IKr-channel blocker resistant VT/VF. (Cardiol J 2007; 14: 355-365

Skuteczność terapii złożonej polegającej na podaniu blokera kanału IKr oraz wykonaniu blokady zwoju gwiaździstego w leczeniu opornych arytmii komorowych u chorych z zatrzymaniem krążenia

Wstęp: W poprzednich doniesieniach autorzy niniejszej pracy dowiedli, że współczynnik skuteczności defibrylacji przy jednoczesnym dożylnym podaniu chlorowodorku nifekalantu (NIF) - selektywnego blokera kanałów szybkiej składowej opóźnionego prostującego prądu potasowego (IKr) wynosił powyżej 75% dla opornego na lignokainę częstoskurczu lub migotania komór (VT/VF) w przebiegu pozaszpitalnego zatrzymania krążenia (CPA). Jednakże dla pozostałych 25% chorych, u których wykonana defibrylacja okazała się nieskuteczna, nie znaleziono efektywnych metod leczenia. Autorzy niniejszej pracy sugerują, że zastosowanie złożonej terapii polegającej na dożylnym podaniu NIF oraz wykonaniu blokady lewego zwoju gwiaździstego (LSGB) jest użyteczne w przypadku defibrylacji VT/VF opornego na działanie NIF. Na podstawie własnych badań retrospektywnych podjęto także próbę oceny skuteczności tej terapii. Metody i wyniki: Do badania włączono kolejnych 272 chorych przyjętych do Kliniki Kardiologii Uniwersytetu Tokai w okresie od kwietnia do grudnia 2006 roku z powodu pozaszpitalnego zatrzymania krążenia. U 55 pacjentów (podczas przyjęcia lub też w przebiegu resuscytacji krążeniowo-oddechowej) stwierdzono VT/VF. Zgodnie z samodzielnie wypracowanymi przez autorów pracy algorytmami prowadzenia resuscytacji krążeniowo-oddechowej NIF (w dawce 0,15-0,3 mg/kg) podawano dożylnie po pierwszej próbie kardiowersji. Oporne na działanie NIF częstoskurcze komorowe/migotania komór wystąpiły u 15 spośród 55 pacjentów. U 11 chorych z powyższej grupy wykonano LSGB oraz podano dożylnie NIF. U 7 osób (64%) po zabiegu LSGB uzyskano powrót rytmu zatokowego. Całkowity powrót do zdrowia zanotowano u 2 chorych. Jednakże w grupie, w której nie wykonano zabiegu blokady lewego zwoju gwiaździstego (grupa nie-LSBG), zmarli wszyscy pacjenci. Wnioski: Terapia złożona polegająca na dożylnym podaniu NIF oraz wykonaniu LSGB okazała się użyteczna w przypadku defibrylacji opornego VT/VF. Jest to potencjalna i innowacyjna strategia leczenia opornego na selektywne blokery kanałów IKr częstoskurczu komorowego/ migotania komór. (Folia Cardiologica Excerpta 2007; 2: 524-536

Circadian Distribution and Autonomic Tone Modulation in Paroxysmal Atrial Fibrillation

Understanding the role played by autonomic tone changes in the initiation of paroxysmal atrial fibrillation (PAF. may be helpful in preventing the occurrence of the arrhythmia. The purpose of this review article is to discuss the relationship between sympathovagal imbalance and the initiation of PAF from past literature and our data regarding circadian distribution and heart rate variability (HRV. analysis in PAF. PAF in non-structural heart disease (NHD. frequently occurs during evening and night hours with a longer duration of each episode, and its initiation is directly associated with an increase in vagal tone. According to our data of HRV analysis in NHD, HF power (indicator of vagal tone. showed a reduction 15 to 30 minutes before PAF, followed by a sharp increase immediately before the onset, suggesting a primary increase in sympathetic tone followed by a marked changes toward vagal predominance. Very few studies have been reported on PAF onset or the modulation of autonomic tone in structural heart disease (SHD). Some studies showed no significant differences in the circadian variation of the onset between NHD and SHD. However, we demonstrated a triphasic circadian pattern with maximum peaks in early morning, late afternoon, and night in SHD, suggesting an association with not only a vagally induced origin but also a sympathecally induced or stress triggered origin in PAF onset in SHD. The occurrence of PAF greatly depends on modulation of autonomic tone and is extremely complicated. Further studies are required to clarify the relationship between the occurrence of PAF and autonomic modulation

Systematic review of the use of intravenous amiodarone and nifekalant for cardiopulmonary resuscitation in Japan

AbstractBackgroundIntravenous amiodarone is considered to be the first-line drug for the treatment of ventricular tachycardia or fibrillation. However, in Japan, nifekalant had been used before the introduction of amiodarone; therefore, most clinical studies on amiodarone use have been small-scale studies. The aim of the present study was to review the literature concerning the actual use of amiodarone and nifekalant in order to evaluate the effects of both drugs and the most appropriate mode of administration.MethodsThe Japan Medical Abstracts Society, PubMed, and Scopus databases were used to identify the reports. The resulting data were used for a systematic review focusing on the effectiveness of amiodarone in comparison with that of nifekalant and the dose differential effect of amiodarone.ResultsThe search returned 9 studies, including 310 patients, that compared the effectiveness of amiodarone and nifekalant, as well as 3 studies, including 108 patients, that analyzed the effectiveness of treatment according to amiodarone dose. Of 418 patients, 187 in whom amiodarone was used for cardiopulmonary resuscitation (CPR) were included in a review that compared the doses recommended by Japanese guidelines 2009 (125mg intravenous [i.v.] over 10min) and the American Heart Association guidelines (300mg bolus i.v.). Amiodarone and nifekalant were equally effective in preventing electrical storm (67% vs. 67%). The defibrillation effect for CPR was also equal in the 2 groups (60% vs. 54%). Hypotension and bradycardia were recorded as adverse effects in the amiodarone group (9.5% and 5.3%), whereas torsades de pointes was observed in the nifekalant group (1.4%). In the analysis of the dose-differential effect of amiodarone, the rates of successful return of spontaneous circulation and discharge survival were higher in the 125-mg slow i.v. group than in the 300-mg bolus i.v. group (76% vs. 53% and 54% vs. 26%, respectively).ConclusionsAmiodarone and nifekalant were equivalent in their prophylactic and defibrillation efficacy. Concerning the initial amiodarone dose, the 125mg intravenous [i.v.] over 10min seemed to be more appropriate for the Japanese population

Inducibility of Ventricular Arrhythmia 1 Year Following Treatment with Heavy Ion Irradiation in Dogs with Myocardial Infarction

Background: Targeted external heavy ion irradiation (THIR) of rabbit hearts 2 weeks after myocardial infarction (MI) reduced the vulnerability of fatal ventricular tachyarrhythmias (VT/VF) in association with the increased connexin43 (Cx43). Increased Cx43 was maintained for at least 1 year in normal rabbits, but the long-term antiarrhythmic effects in the MI model are unknown. We investigated the propensity for late potentials and VT/VF inducibility.Methods: Intracoronary injection of microspheres was performed to induce nontransmural MI in anesthetized eight beagles. Four beagles were treated with THIR (12C6+, 15 Gy) 2 weeks later (MI + THIR group), and four without THIR served as controls (MI group). Signal-averaged electrocardiography, programmed electrical stimulation, immunohistochemical analysis, and echocardiograms were performed at 1 year.Results: Filtered QRS duration was exacerbated after MI and remained unchanged for 1 year in the MI group (118 ± 1.4 ms), but significantly returned toward baseline in the MI + THIR group (109 ± 6.9 ms). Similarly, root mean square voltage of the last 40 ms was exacerbated after MI, but recovered after THIR. VT/VF inducibility decreased to 25% in the MI + THIR group compared with 100% in the MI group. Immunostaining Cx43 expression in cardiac tissues significantly increased by 24–45% in the MI + THIR group. Left ventricular ejection fractions remained within the normal range in both groups.Conclusion: A single exposure of the dog heart to 12C irradiation attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression

Changes in arrhythmogenic properties and five-year prognosis after carbon-ion radiotherapy in patients with mediastinum cancer

Introduction: Carbon-ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon-ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra-cardiac cancer treated with carbon-ion radiotherapy that included irradiating the heart. Methods and Results: In April–December 2009, eight patients were prospectively enrolled (including two male, aged 68.4 ± 17.2 years). They were treated with 44–72 Gray equivalent (GyE), with their hearts exposed to 1.3–19.1 GyE. High-resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre-existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five-year follow-up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events. Conclusion: Although this preliminary study has several limitations, carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue