Neural selectivity,efficiency, and dose equivalence in deep brain stimulation through pulse width tuning and segmented electrodes

BackgroundAchieving deep brain stimulation (DBS) dose equivalence is challenging, especially with pulse width tuning and directional contacts. Further, the precise effects of pulse width tuning are unknown, and recent reports of the effects of pulse width tuning on neural selectivity are at odds with classic biophysical studies.MethodsWe created multicompartment neuron models for two axon diameters and used finite element modeling to determine extracellular influence from standard and segmented electrodes. We analyzed axon activation profiles and calculated volumes of tissue activated.ResultsWe find that long pulse widths focus the stimulation effect on small, nearby fibers, suppressing distant white matter tract activation (responsible for some DBS side effects) and improving battery utilization when equivalent activation is maintained for small axons. Directional leads enable similar benefits to a greater degree. Reexamining previous reports of short pulse stimulation reducing side effects, we explore a possible alternate explanation: non-dose equivalent stimulation may have resulted in reduced spread of neural activation. Finally, using internal capsule avoidance as an example in the context of subthalamic stimulation, we present a patient-specific model to show how long pulse widths could help increase the biophysical therapeutic window.DiscussionWe find agreement with classic studies and predict that long pulse widths may focus the stimulation effect on small, nearby fibers and improve power consumption. While future pre-clinical and clinical work is necessary regarding pulse width tuning, it is clear that future studies must ensure dose equivalence, noting that energy- and charge-equivalent amplitudes do not result in equivalent spread of neural activation when changing pulse width.     

Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Diagnoses and Surgical Results in 12 Pediatric Patients

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital condition. It responds well to early diagnosis and treatment, but otherwise the prognosis is poor. We present our case series of 12 patients (mean age, 2 ± 2.58 yr; age range, 2 mo–8 yr), emphasizing the diagnostic process and discussing our surgical results. The diagnosis of ALCAPA should be suspected in infants who have dilated cardiomyopathy with electrocardiographic changes that suggest ischemia, and in older children who have isolated mitral regurgitation. When clinical suspicion is high, the results of 2-dimensional echocardiography combined with color-flow Doppler studies in expert hands can establish the diagnosis, thus avoiding angiography in critically ill infants. The treatment of choice in our patients was transfer and reimplantation of the left coronary artery onto the ascending aorta. There were 2 deaths: both were infants in extremis who underwent emergency surgery. An older child with severe ventricular dysfunction was given mechanical ventricular assistance and then heart transplantation. As of this report, all 10 survivors remained well and asymptomatic.     

The challenges in scoring hypopneas in children: is pulse wave amplitude drop the answer?

BackgroundIdentifying electroencephalogram (EEG) cortical arousals are crucial in scoring hypopneas and respiratory efforts related arousals (RERAs) during a polysomnogram. As children have high arousal threshold, many of the flow limited breaths or hypopneas may not be associated with visual EEG arousals, hence this may lead to potential underestimation of the degree of sleep disordered breathing. Pulse wave amplitude (PWA) is a signal obtained from finger photoplethysmography which correlates directly to finger blood flow. The drop in PWA has been shown to be a sensitive marker for subcortical/autonomic and cortical arousals. Our aim was to use the drop in PWA as a surrogate for arousals to guide scoring of respiratory events in pediatric patients.MethodsTen polysomnograms for patients between the ages of 5–15 years who had obstructive apnea-hypopnea indices between 1 and 5 events/hour were identified. Patients with syndromes were excluded. A drop in PWA signal of at least 30% that lasted for 3 s was needed to identify subcortical/autonomic arousals. Arousals were rescored based on this criteria and subsequently respiratory events were rescored. Paired t-tests were employed to compare PSG indices scored with or without PWA incorporation.ResultsThe sample of 10 children included 2 females, and the average age was 9.8 ± 3.1 years. Overall, polysomnography revealed an average total sleep time of 464.1 ± 25 min, sleep efficiency of 92% +/−4.2, sleep latency of 19.6 ± 17.0 min, rapid eye movement (REM) latency 143 ± 66 min, N1 3.9% +/−2.0, N2 50.3% +/−12.0, N3 28.2% +/−9.1, REM 16.7% +/−4.0, and wakefulness after sleep onset (WASO) 18.1 ± 7.5 min. Including arousals from PWA changes, respiratory indices significantly increased including total AHI (2.3 ± 0.7 vs 5.7 ± 2.1, p < 0.001), obstructive AHI (1.45 ± 0.7 vs 4.8 ± 1.8, p < 0.001), and RDI (2.36 ± 0.7 vs 7.6 ± 2.0, p < 0.001). Likewise, total arousal index was significantly higher (8.7 ± 2.3 vs 29.4 ± 6.5, p < 0.001).ConclusionsThe drop in pulse wave amplitude signal is a useful marker to guide scoring arousals that are not otherwise easily identified in pediatric polysomnography and subsequently helped in scoring respiratory events that otherwise would not be scored. Further studies are needed to delineate if such methodology would affect clinical outcome.     

The Importance of Venous Return in Starling‐Like Control of Rotary Ventricular Assist Devices

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling‐like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC‐P) against an SLC with a vertical VRL (SLC‐V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC‐P produced no overshoot or oscillations following step changes in preload, whereas SLC‐V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC‐V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Development and function of tissue resident macrophages in mice

Macrophages are important for tissue development, homeostasis as well as immune response upon injury or infection. For a long time they were only seen as one uniform group of phagocytes with a common origin and similar functions. However, this view has been challenged in the last decade and revealed a complex diversity of tissue resident macrophages. Here, we want to present the current view on macrophage development and tissue specification and we will discuss differences as well as common patterns between heterogeneous macrophage subpopulations.     

启发式教学在生理学教学中的应用研究

针对生理学课程理论抽象、实验操作复杂等特点,阐述了启发式教学方法取代传统填鸭式教学方法的必然性。因生理学教学难度大、实验操作条件高,故着重介绍了问答式、讨论式、演绎式、归纳式、直观式等五种启发式教学方法在生理学教学中的应用。     

老年高血压患者脉压与急性心肌梗塞的关系

目的探讨老年原发性高血压（ET）患者脉压与急性心肌梗塞（AMI）的关系。方法观测45例老年高血压病合并急性心肌梗塞患者的收缩压（SBP）、舒张压（DBP）及脉压（PP），以31例老年单纯高血压患者（冠脉造影排除冠心病）作对照组，进行比较。结果并发急性心肌梗塞组，其脉压较单纯高血压组明显增高。结论脉压与老年人急性心肌梗塞密切相关，对老年人高血压的治疗更要注重控制脉压。     

多普勒组织成像技术在评价高血压左室舒张功能中的应用

目的 :应用多普勒组织成像 (DTI)技术检测二尖瓣环舒张期运动速度来评介原发性高血压左室舒张功能 ,探讨DTI的临床应用价值。方法 :2 0例原发性高血压和 2 0例年龄相似的健康者 ,应用DTI技术对二尖瓣环室间隔侧的运动速度进行测定 ,并与常规二尖瓣血流脉冲多普勒 (PW)检测结果对照分析。结果 :PW高血压组与对照组比较 ,峰值速度E、A及E/A明显低于对照组 ,差异显著 (P <0 0 1) ;DTI高血压组与对照组比较 ,峰值速度Ea、Aa及Ea/Aa明显低于对照组 ,差异非常显著 (P <0 0 0 1)。PW、DTI两组相同部位间比较 ,高血压组低于对照组。结论 :DTI技术评价高血压左室舒张功能比常规脉冲多普勒二尖瓣血流参数更敏感