Spatial steering of deep brain stimulation volumes using a novel lead design.

OBJECTIVE: To investigate steering the volume of activated tissue (VTA) with deep brain stimulation (DBS) using a novel high spatial-resolution lead design. METHODS: We examined the effect of asymmetric current-injection across the DBS-array on the VTA. These predictions were then evaluated acutely in a non-human primate implanted with the DBS-array, using motor side-effect thresholds as the metric for estimating VTA asymmetries. RESULTS: Simulations show the DBS-array, with electrodes arranged together in a cylindrical configuration, can generate field distributions equivalent to commercial DBS leads, and these field distributions can be modulated using field-steering methods. Stimulation with implanted DBS-arrays showed directionally-selective muscle activation, presumably through spread of stimulation fields into portions of the corticospinal tract lying in the internal capsule. CONCLUSIONS: Our computational and experimental studies demonstrate that the DBS-array is capable of spatially selective stimulation. Displacing VTAs away from the lead's axis can be achieved using a single simple and intuitive control parameter. SIGNIFICANCE: Optimal DBS likely requires non-uniform VTAs that may differentially affect a nucleus or fiber pathway. The DBS-array allows positioning VTAs with sub-millimeter precision, which is especially relevant for those patients with DBS leads placed in sub-optimal locations. This may present clinicians with an additional degree of freedom to optimize the DBS therapy.

Isoflurane suppresses central cardiac parasympathetic activity in rats: a pilot study.

BACKGROUND: Intraoperative circulatory stability is a function of both cardiac parasympathetic activity and cardiac and vascular sympathetic activity; however, cardiac parasympathetic activity is rarely considered. This experiment addresses the effect of isoflurane on central cardiac parasympathetic control, i.e., cardiac vagal motoneurons (CVM), which are located in the nucleus ambiguous of the brain stem and project to the sinus node. METHODS: In urethane-anesthetized rats, the single unit activity of CVM, antidromically identified from the craniovagal cardiac branch, was observed following the introduction of isoflurane. Isoflurane was introduced slowly over 10 minutes to achieve 2% end tidal CO2 (ETCO2) RESULTS: Following the introduction of isoflurane (2% ETCO2), all CVM were almost entirely silenced (N=6 cells in 6 different rats, 1.9 ±2.4 vs. 0.2 ±0.3 Hz, P<0.05). CONCLUSION: The data obtained with antidromically identified cardiac vagal motoneurons confirm data obtained previously with whole vagal nerve recordings. The authors speculate on how the blunting of the cardiac parasympathetic activity by isoflurane that was observed in rats may impact intraoperative circulatory stability in humans.

Recruitment of cardiac parasympathetic activity: effects of clonidine on cardiac vagal motoneurones, pressure lability, and cardiac baroreflex slope in rats.

BACKGROUND: Association of low cardiac vagal activity and poor outcome is demonstrated in the cardiology setting. This has not been addressed in the postoperative setting. Cardiac vagal motoneurones (CVMs) in the brain stem generate sinus arrhythmia. They may reduce blood pressure (BP) variability ('pressure lability'). An alpha-2 agonist, clonidine, was administered to assess whether cardiac vagal activity could be recruited from a very low baseline activity, increase the sensitivity of the cardiac baroreflex and sinus arrhythmia, and reduce the pressure lability. METHODS: In ventilated anaesthetized rats, single-unit activity from antidromically identified CVMs was recorded. Given complex interactions within the cardiac ganglion, a peripherally acting beta-blocker, atenolol, was administered before clonidine. RESULTS: Atenolol 2 mg kg(-1) i.v. did not change systolic BP (SBP), CVM firing rate and slope of the cardiac baroreflex analysed at CVM (SBP-CVM unit activity relationship) level, or at the heart level (SBP-RR interval relationship) but evoked a significant bradycardia. In the presence of atenolol 2 mg kg(-1) h(-1), clonidine 10-100 microg kg(-1) i.v. evoked a significant reduction in SBP, a large increase of CVM firing rate from a very low base line [0.16 (sd 0.28) to 1.37 (1.21) spikes s(-1), n=7 cells], and increased the slope of the cardiac baroreflex analysed at the CVM level or at the heart level. sds of SBP were reduced, and that of RR interval was increased. CONCLUSIONS: Following peripheral beta-blockade, clonidine activated CVMs from a very low baseline, increased the slope of the cardiac baroreflex and sinus arrhythmia, and reduced pressure lability.

Effect of systemic B-type natriuretic peptide on cardiac vagal motoneuron activity.

Intravenous B-type natriuretic peptide (BNP) enhances the bradycardia of reflexes from the heart, including the von Bezold-Jarisch reflex, but its site of action is unknown. The peptide is unlikely to penetrate the blood-brain barrier but could act on afferent or efferent reflex pathways. To investigate the latter, two types of experiment were performed on urethane-anesthetized (1.4 g/kg iv) rats. First, the activity was recorded extracellularly from single cardiac vagal motoneurons (CVMs) in the nucleus ambiguus. CVMs were identified by antidromic activation from the cardiac vagal branch and by their barosensitivity. Phenyl biguanide (PBG), injected via the right atrium in bolus doses of 1-5 mug to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol.kg(-1).min(-1) iv) significantly enhanced both the CVM response to PBG (n = 5 rats) and the reflex bradycardia, but the log-linear relation between those two responses over a range of PBG doses was unchanged by BNP. The reflex bradycardia was not enhanced in five matched time-control rats receiving only vehicle infusions. In five other rats the cervical vagi were cut and the peripheral right vagus was stimulated supramaximally at frequencies of 1-20 Hz. The bradycardic responses to these stimuli were unchanged before, during, and after BNP infusion. We conclude that systemic BNP in a moderate dose enhances the von Bezold-Jarisch reflex activation of CVM, in parallel with the enhanced reflex bradycardia. That enhancement is due entirely to an action before the vagal efferent arm of the reflex pathway.

[The confirmation of a correlation between atmospheric air pollution with sedimentation dusts and pediatric morbidity]. / Cercetari privind confirmarea corelatiei dintre poluarea aerului atmosferic cu pulberi sedimentabile si morbiditatea infantila.

The obtained results support the data in the literature on the correlation of air pollution with morbidity in general and with the infantile one, particularly by respiratory diseases in urban areas of Iasi district. The maintenance of the pollutants under the minimum admitted concentration by corresponding measures at the level of pollution source together with increasing the general resistance of the population are necessary.