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 72.5 ± 13.0 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.

     

Real-time imaging of human cortical activity evoked by painful esophageal stimulation

BACKGROUND & AIMS: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. METHODS: In 16 healthy subjects (8 men; mean age, 30.2 +/- 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 +/- 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. RESULTS: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (approximately 85 ms). Significantly later activity was seen in the anterior insula (approximately 103 ms) and cingulate cortex (approximately 106 ms; P=.0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P=.16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P=.001). No sex differences were seen for psychophysical or neurophysiological measures. CONCLUSIONS: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate-brain regions that process the affective aspects of esophageal pain-occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity.     

奎尼丁所致异常U波与早期后除极的相关性研究

静脉注射中毒剂量奎尼丁建立ＱＴＵ间期延长综合征动物模型，应用接触电极导管记录犬左室心内膜单相动作电位（ＭＭ），以研究早期后除极（ＥＡＤ）与Ｕ波的关系。用药后１１条犬体表心电图上均出现异常Ｕ波，同步记录的ＭＡＰ３相上可见高振幅ＥＡＤ，二者振幅高度相关（ｒ＝０．９８），峰值时间基本一致。Ｕ波与ＥＡＤ均具有间歇依赖特性。用药后ＱＴＵ间期由对照的２４０±１９ｍｓ延长至４１５±７４ｍｓ，ＭＡＰ复极至９０％的时间（ＭＡＰＤ＿（９０））由对照的２２３±１８ｍｓ延长至３４８±８２ｍｓ，二者相关良好（ｒ＝０．９８）．用药后，１条犬发生频发成对室性早搏，呈“ＲｏｎＴＵ”现象。ＭＡＰ记录显示提前除极起源于ＥＡＤ峰值近处。无自发性尖端扭转型室性心动过速发生。研究结果表明：ＭＡＰ技术是研究在体心脏抗心律失常药物作用机理的可靠方法；体表心电图上异常Ｕ波可能来源于ＭＡＰ上的ＥＡＤ；ＭＡＰＤ９０是较ＱＴＵ间期更为精确的指标；奎尼丁诱发心律失常机制可能为触发活动。     

Contribution of long axis motion of left ventricular outflow to calculation of left ventricular stroke volume

Stroke volume can be calculated by using noninvasive Doppler techniques. The products of pulsed Doppler stroke distance of left ventricular outflow and left ventricular outflow area can often be used to calculate stroke volume. However, left ventricular outflow also moves longitudinally toward the apex of the ventricle during systole, so that zero velocity flow cannot be detected by the usual pulsed Doppler studies. We evaluated the contribution of these zero velocity flow to the noninvasive estimation of left ventricular stroke volume in 20 patients with left ventricular disease and in 20 age matched healthy controls. Left ventricular stroke distance was calculated by summing the Doppler stroke distance and the outflow long axis motion. The percentage of zero velocity flow for total stroke volume was calculated in each group. Cardiac output was also measured by thermo-dilution technique. The percentage of zero velocity flow for total noninvasive stroke volume in patients with left ventricular disease was 2.5±1.1 ml (4.0±1.5%), significantly lower than in normal subjects, 3.6±1.0 ml (5.5±1.5%) (p<0.05). These long axis motions are significantly reduced, especially in left ventricular disease. Amplitudes of the left ventricular outflow long axis motion were correlated with Doppler stroke distance in all (r=0.54, p<0.01). In patients with myocardial infarction, stroke volume by thermo-dilution methods and calculated stroke volume showed good correlation both only by Doppler stroke distance (y=1.044x+0.547, r=0.968) and by Doppler and long axis motion (y=0.989x+0.521, r=0.974). Compared with stroke volume measured by thermodilution method, stroke volume calculated only by Doppler stroke distance was underestimated. We thus demonstrated the influence of zero velocity flow on left ventricular outflow both in patients with left ventricular disease and in normal subjects.     

Acute and chronic electrophysiologic changes surrounding radiofrequency lesions

INTRODUCTION: Arrhythmia recurrences may occur after acutely successful radiofrequency (RF) ablation, suggesting reversible electrophysiologic effects on myocardial tissue. The aim of this study was to examine the electrophysiologic changes occurring in myocardium surrounding acute and chronic RF lesions. METHODS AND RESULTS: RF lesions (60 degrees C for 30 sec) were produced on the epicardial left ventricular surface of 35 isolated perfused rabbit hearts. Microelectrode transmembrane action potential recordings were made at 0.25-mm intervals along the epicardial (n = 20) or intramural (n = 6) aspects of the lesions for up to 3.5 mm from the lesion edge at baseline and after acute RF lesion formation. In nine hearts, chronic lesions were studied with epicardial recordings made 22 +/- 13 days after RF lesion formation. In the acute hearts at 600-msec paced cycle length, action potential duration at 50% repolarization (APD50) and 90% repolarization (APD90) were reduced by up to 41% and 19%, respectively, within 2.5 mm from the lesion edge (all P < 0.05). Maximal action potential amplitude (APDmax) was reduced by 16% at 0.25 mm from the lesion edge (P = 0.009) but dV/dt was not changed. Conduction time (CT) from the outermost recording site to the lesion edge (3.5-mm distance) was reduced from 16 +/- 3 msec at baseline to 13 +/- 4 msec post ablation (P = 0.006). Qualitatively similar findings occurred at 200-msec cycle lengths. There were no changes in APD, CT, APDmax, or dV/dt surrounding the chronic lesions at 22 +/- 13 days after lesion formation. CONCLUSION: Acutely following RF energy delivery, APD, APDmax, and CT are reduced in the tissue surrounding the lesion. These electrophysiologic changes resolve within 22 +/- 13 days of lesion formation.     

Organ-cultured chick embryonic hearts of various ages. I. Electrophysiology

Tetrodotoxin (TTX)-insensitive slow Na⁺ channels are converted or replaced by TTX-sensitive fast Na⁺ channels during normal embryonic development of the chick heart, and rapid reversion occurs in monolayer cell culture (denervated). Fast Na⁺ channels first appear at 4 to 5 days, which is about the time of innervation. Studies were done to determine whether changes in cation channels will occur while hearts are in organ culture. To test whether fast Na⁺ channels will develop in the absence of innervation, hearts from chick embryos 2 to 3 days old were placed into culture for 6 to 8 days. Although the resting potentials of the ventricular cells were about the same as those obtained from fresh 8 to 10 day old hearts, the maximum rate of rise of the action potentials ($\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$) did not reach the high value (about 80 V/s) expected from the calendar age. Instead $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ remained at about the same value (12 V/s) that the hearts had when placed into culture. The action potentials were completely insensitive to TTX. The slow channels admit primarily Na⁺ and not Ca²⁺ because Mn²⁺ (1 mm) and lowering [Ca²⁺]₀ to nearly zero by EGTA did not diminish $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$. To test whether the fast Na⁺ channels disappear in organ culture, hearts from embryos 15 to 19 days old were cultured as whole hearts or minced hearts. The whole hearts survived well for 1 to 6 days; the $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ values remained high (～ 100 V/s), and TTX completely blocked the action potentials. The minced hearts had variable $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ values, depending on the piece. Those pieces which had a low $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ were insensitive to TTX, and those which had a high or intermediate $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$, were reduced to 5 to 20 V/s by TTX; these persisting responses in TTX were not blocked by Mn²⁺ or zero [Ca²⁺]₀. The results suggest that, while in organ culture, young hearts do not gain fast Na⁺ channels or lose the slow Na⁺ channels that would normally occur in situ. Organ-cultured old hearts left intact do not lose their fast Na⁺ channels. Thus, young or old hearts retain the channels that they originally possessed when placed into culture. Mincing initiates a gain of slow Na⁺ channels, and in some pieces, a partial loss of fast Na⁺ channels.     

低血钾性恶性心律失常的心室晚电位研究

23只杂种犬,14只用聚苯乙烯磺酸钠灌肠造成低血钾,60分钟后注射小剂量肾上腺素(10μg/kg),低钾组全部出现心律失常,其中11只出现室性心动过速/心室颤动。低钾组的体表心室晚电位(VLP)总QRS时间(TQRS)明显延长,最后40毫秒均方根电压(RMS_(40))振幅明显降低,趋向于晚电位阳性改变。同时电镜显示心肌超微结构损伤,线粒体钙含量升高,心肌细胞膜Na~+-K~+-ATP酶活性抑制,磷脂酶A_2活性增加及膜磷脂降解,这些结构和代谢改变可能是低钾性心肌损伤、心律失常和VLP改变的机理。     

Combined imaging of molecular function and morphology with PET/CT and SPECT/CT: Image fusion and motion correction

Imaging of the cardiovascular system with a combination of positron emission tomography (PET) and computer tomography (CT) or with a combination of single-photon emission computerized tomography (SPECT) and CT holds great promise for the future. Owing to the movement of the heart and the great vessels due to heart contraction and respiration this is, however, not straightforward. This article provides an overview over the principles of combined PET/CT or SPECT/CT imaging. It points out technical challenges inherent in imaging of cardiovascular system and presents possible solutions that allow for optimal fusion and motion correction of the combined molecular, functional and morphological image data.     

Evaluation of residual hearing in cochlear implants candidates using auditory steady-state response

Conclusion: The correlations between behavioral and auditory steady-state response (ASSR) thresholds were significant at 500, 1000, 2000, and 4000 Hz. ASSR presented high sensitivity and specificity in the detection of residual hearing in cochlear implant candidates when compared with warble-tone audiometry. Objectives: To assess residual hearing in cochlear implant candidates by comparing the electrophysiological thresholds obtained in dichotic single-frequency ASSR with behavioral thresholds at 500, 1000, 2000, and 4000 Hz. Methods: This was a comparative study between ASSR and warble-tone audiometry thresholds in 40 cochlear implant candidates (80 ears) before cochlear implantation with bilateral severe-to-profound sensorineural hearing loss. Results: Thresholds were obtained in 62.5% of all frequencies evaluated in warble-tone audiometry and in 63.1% in the ASSR. ASSR sensitivity was 96% and specificity was 91.6%. Mean differences between behavioral and ASSR thresholds did not reach significance at any frequencies. Strong correlations between behavioral and ASSR thresholds were observed in 500, 1000, and 2000 Hz and moderate in 4000 Hz, with correlation coefficients varying from 0.65 to 0.81. On 90% of occasions, ASSR thresholds were acquired within 10 dB of behavioral thresholds.     

Neonatal chest wall suspension splint: a novel and noninvasive method for support of lung volume

Surfactant and musculoskeletal immaturity results in lower compliance of the lung relative to the chest wall, with clinical manifestations of low lung volume, marked chest wall retractions (CWR), and thoracoabdominal asynchrony. Inspiratory efforts are dissipated on distorting the chest wall inward rather than recruiting lung volumes. The current study tests the hypothesis that a novel neonatal chest wall suspension splint (SP), designed to provide stability to the compliant chest wall, would reduce inspiratory chest wall retractions and improve lung volumes. Nine preterm infants (29 +/- 1 SE weeks of gestation; 1.59 +/- 0.27 SE kg study weight) were studied at 16 +/- 5 SE days of life at baseline (BL) and following application of the front plate (FP) and the full SP (Hug n Snug Neonatal Chest Splint, Respironics, Inc.). Phase angle of thoracoabdominal motion, CWR, functional residual capacity (FRC), and pulmonary function were evaluated during spontaneous breathing. Compared to BL, there was a significant decrease in anterior CWR (2.21 +/- 0.91 SE vs. 0.25 +/- 0.09 SE mm; P < 0.05), an increase in FRC (16.6 +/- 2.8 SE vs. 27.8 +/- 5.5 SE ml/kg; P < 0.05) and tidal volume (4.8 +/- 1.5 SE vs. 7.3 +/- 1.4 SE ml/kg; P < 0.05), minimal effect on pulmonary compliance (1.98 +/- 0.50 SE vs. 1.72 +/- 0.30 SE ml/cmH2O/kg), and a trend for a decrease in phase angle (128.4 +/- 10.9 SE vs. 111.8 +/- 19.3 SE) with the application of the splint. FRC correlated inversely with severity of CWR across all conditions (P < 0.05, r = -0.68). Phase angle was directly correlated to anterior CWR (r = 0.72; P < 0.05) and correlated inversely with FRC (P < 0.005; r = -0.56). We speculate that by improving CW stability, the use of this splint may reduce the energetic requirements of breathing and, potentially, the need for more invasive ventilatory support in the neonate.