Parasympathetic activity in brain death: effect of apnea on heart rate variability

Background : Power spectral analysis of heart rate variability is a useful monitoring of brain-damaged patients. However, the effect of artificial ventilation is not clearly demonstrated in assessing vagal activity because the locus of its activity is originated close to the respiratory center in the brain stem. We studied heart rate variability during artificial ventilation and apnea test as part of an assessment of brain death.
Methods : Ten adult patients with severe brain damage were studied. Power spectral analysis of heart rate variability from electrocardiographic R-R intervals was integrated to compare spectral components before, during and after the apnea test. Before the test, circulatory and blood gas variables and electrocar-diographic recording were obtained under controlled mechanical ventilation at a rate of 12 and 18 (/min), each for 5 min. Measurements were made for 10 min during the apnea test, and repeated thereafter as before the test. Power spectral analysis based on fast Fourier transformation was made by integrating each low- (LF: 0.04-0.15 Hz) and high- (HF: 0.15-0.40 Hz) frequency band areas. LF was assessed as sympathetic and para-sympathetic nervous activity, and HF as respiratory-related parasympathetic vagal activity. The HF/LF ratio showed sym-pathovagal balance.
Results : All patients were assessed as brain dead. During apnea, PaCo₂ (P<0.05) and LF (P<0.05) increased, and pH (P<0.01) and HF/LF ratio (P<0.05) decreased. Heart rate, mean arterial pressure, PaO₂ and HF remained consistent throughout.
Conclusion : It was shown that sympathovagal balance was inclined to be sympathotonic during apnea, and that there were no changes in the respiratory-related vagal activity in spite of stopping artificial ventilation.     

Accuracy of the pleth variability index to predict fluid responsiveness depends on the perfusion index

Background: Respiratory variations in plethysmographic waveform amplitudes derived from pulse oximetry are believed to predict fluid responsiveness. The non‐invasive pleth variability index (PVI) is a variable based on the calculation of changes in the perfusion index (PI). The aim of the following study was to examine whether the predictive power of PVI depends on different values of PI. Methods: Eighty‐one patients undergoing elective coronary artery surgery were studied before operation: at baseline after induction of anaesthesia and during passive leg raising (PLR). Each patient was monitored with central venous pressure (CVP), the PiCCO monitor and the non‐invasive Masimo monitoring system. Stroke volume index by transpulmonary thermodilution (SVI_TPTD), pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance index (SVRI) were measured using the PiCCO monitoring system. PI and PVI were obtained by pulse oximetry. Results: Responders were defined to increase their SVI_TPTD>15% after PLR. The highest area under the curve (AUC) was found for PPV (AUC: 0.83, P<0.0001) and SVV (AUC: 0.72, P=0.002), in contrast to PVI (AUC: 0.60, P=0.11) and CVP (AUC: 0.60, P=0.13). The accuracy of PVI to predict fluid responsiveness was improved on analysing patients with higher PI values. PI of about 4% (n=45) achieved statistical significance (AUC: 0.72, P=0.01). Conclusion: The PVI was not able to predict fluid responsiveness with sufficient accuracy. In patients with higher perfusion states, the PVI improved its ability to predict haemodynamic changes, strongly suggesting a relevant influence of the PI on the PVI.     

The effects of feature attention on prestimulus cortical activity in the human visual system

Covert attention affects prestimulus activity in the visual cortex. Although most studies investigating neural mechanisms of attention have focused on the effects of spatial attention, attention can also be directed to particular features. To investigate the spatiotemporal nature of feature attention, we measured subjects' brain activity using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) while subjects attended to color or motion of a stimulus based on a visual cue, which was presented 1 s before the stimulus onset. We used the hierarchical Bayesian method that allows us to estimate cortical currents with MEG and fMRI data in the order of millimeters and milliseconds. When subjects attended to color, activity within the color-sensitive area (fusiform gyrus) was selectively enhanced within the prestimulus period. By contrast, when subjects attended to motion, activity within the motion-sensitive area (middle temporal gyrus) was selectively enhanced during this period. This effect was not seen in frontal, parietal, and lower visual areas. Additionally, this effect was transient rather than sustained, suggesting that it differs from temporal aspects of spatial attention. These results suggest that, although both spatial and feature attention modulate prestimulus activity within specific visual areas, neural mechanisms underlying these effects might be different.     

肾上腺切除对5/6肾切除大鼠肾脏的保护作用

目的通过切除5／6肾切除大鼠的肾上腺,探讨醛固酮对慢性肾脏疾病发生及发展的作用。方法雄性Wister大鼠分成5组:(1)假手术组(SHAM组);(2)5／6肾切除组(SNX组); (3)SNX+双肾上腺切除组(ADX组);(4)ADX+地塞米松组(DXM组);(5)ADX+地塞米松+醛固酮组(ALDO组)。所有大鼠自由饮用生理盐水,于成模第8周测定大鼠收缩压、各项血尿指标及肾小球硬化程度。应用Western印迹和实时定量PCR检测大鼠肾皮质TGF-β1、醛固酮受体 (MR)及保护MR的酶11β-羟类固醇脱氢酶2(11β-HSD2)的mRNA表达水平。结果 SNX组大鼠表现为明显的白蛋白尿、高血压、肾小球硬化、肾皮质TGF-β1表达升高,血醛固酮水平是 SHAM组的4倍以上。与SNX组比较,ADX组大鼠血浆醛固酮水平明显下降,同时病变明显改善 [尿白蛋白(mg／24 h)19．7±2．0比31．7±1．7,P<0．01;收缩压(mmHg)173．8±4．3比210．4±4．1,P <0．01;肾小球硬化指数38．2±7．9比92．3±6．7,P<0．01;TGF-β1 3．8±0．6比10．3±1．2,P< 0．01]。ALDO组的血浆醛固酮水平为SHAM组的近2倍,与ADX组比较,以上病变又加重[尿白蛋白(mg／24 h)24．9±1．4,收缩压(mmHg)201．5±4．5,肾小球硬化指数88．1±7．2,TGF-β1 5．8± 0．6,P均<0．01]。肾脏皮质MR mRNA在SNX组的表达明显增加;在ADX组明显下降[SNX(复制数／百万GAPDH)39866．7±10579．0比SHAM 2366．7±446．3,P<0．05;比ADX 22100．0±4435．7, P<0．05]。然而,11β-HSD2 mRNA表达和MR相反,SNX组为9150．0±969．9,明显低于SHAM组 (48100．0±9315．2,P<0．05);而ADX组的表达比SNX组显著升高(30066．7±5150．2,P<0．05)。 4个实验组大鼠肾脏Ccr和肾重／体重无显著性差别。结论醛固酮参与慢性肾脏病变的进展, 其对肾小球损伤的作用除血流动力学效应外,还可能存在非血流动力学的直接致纤维化作用。     

The invasiveness in vitro of brain tumour derived-cells depends on their micro-eco system

Summary In order to investigate the invasiveness of brain tumours, fragments of freshly resected tumours are transferred into cell culture vessels to form monolayers.The tumour derived monolayer cells are tested in two different in vitro assays for invasiveness: the collagen type I gel¹³ and the embryonic chick heart⁹. Nine of the 10 tumour derived cells infiltrated into the collagen gel, independently of their clinical malignancy. Only 4 of the 10 tumour derived cells invaded the embryonic chick heart. Invasion into chick heart in vitro correlated with malignancy in vivo. The results speak for the hypothesis that the micro environment of the embryonic chick heart allows expression of the invasive character of the brain tumour cells, while the collagen type I in contrast indicates only cell motility.     

Traumatic coagulopathy: the effect of brain injury

Traumatic coagulopathy has several possible mechanisms. In traumatic brain injury (TBI), the principal process involves the release of tissue factor (TF). There is no agreement how common this mechanism is following general trauma. Furthermore, when TF-induced coagulopathy occurs, it is unknown whether the source of TF (TBI or extracranial trauma) influences the course of coagulopathy. We undertook this investigation to address both questions. The temporal course of prothrombin times (PTs) were recorded in a group (n = 441) with isolated TBI (head Abbreviated Injury Scale [AIS] >or= 3, non-head AIS < 3) and a group (n = 101) with extracranial trauma (non-TBI; non-head AIS >or= 3; head AIS < 3). Data were arranged according to preset time intervals after injury. The PT values in both groups were elevated and not significantly different for the first 12 h after trauma. Values then fell to normal in TBI patients, but remained elevated in non-TBI injury. Traumatic coagulopathy can be explained at least in part by TF release into the general circulation with activation of the coagulation cascade in both TBI and non-TBI. We hypothesize that the different time courses of coagulopathy represented by PT values in these populations were due to reconstitution of the blood-brain barrier, although further investigation is warranted. Peripheral hematologic studies may not reflect persistent coagulopathy in cerebral circulation.     

The effect of nitric oxide inhibition on blood pressure depends on rat strain

BACKGROUND: Nitric oxide is a continuously released endothelium-derived vasodilator and plays an important role in the maintenance of blood pressure (BP). Rat strains appear to differ in their resting BP and their response to the intravenous administration of N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor. The presence of diabetes and hypertension also leads to differences in BP responses to l-NAME. We postulated that the contribution of NO to resting BP varies between rat strains and certain strains may be more sensitive to the effects of NO blockade. METHODS: Blood pressure was continuously measured using a carotid arterial catheter and the responses to l-NAME were compared in anesthetized Lewis and Sprague-Dawley rats during a 2-h control period and a 2-h experimental period. l-NAME was given by a 50 mg/kg bolus followed by a 10 mg/kg/h infusion via a mesenteric vein. RESULTS: During the control period, the Lewis animals had lower systolic and diastolic BPs of 103 +/- 1 and 80 +/- 1 mm Hg compared with 127 +/- 1 and 105 +/- 1 mm Hg measured in Sprague-Dawley rats (P < 0.01). Although l-NAME infusion increased systolic BP in both strains compared with control values (P < 0.00005), the magnitude was significantly greater in Sprague-Dawley than Lewis animals (P = 0.0142); additionally, the BP was unstable in the Lewis animals. Furthermore, pulse pressure decreased during l-NAME in Lewis animals but increased in Sprague-Dawley animals (P < 0.00005). There were no significant changes in serum concentrations of aspartate transaminase nor of nitrite plus nitrate after l-NAME in either group. CONCLUSION: These results indicate that the effect of l-NAME on systemic BP differs markedly in Sprague-Dawley and Lewis rats, suggesting that the role of nitric oxide in regulation of resting vascular resistance may differ significantly between these rat strains. Rat strain is an important consideration for valid comparisons between studies.     

The definition of community integration: perspectives of people with brain injuries

Despite considerable attention to community integration and related topics in the past decades, a clear definition of community integration continues to elude researchers and service providers. Common to most discussions of the topic, however, are three ideas: that integration involves relationships with others, independence in one s living situation and activities to fill one s time. The present study sought to expand this conceptualization of community integration by asking people with brain injuries for their own perspectives on community integration. This qualitative study resulted in a definition of community integration consisting of nine indicators: orientation, acceptance, conformity, close and diffuse relationships, living situation, independence, productivity and leisure. These indicators were empirically derived from the text of 116 interviews with people with moderate-severe brain injuries living in the community. Eighteen adults living in supported living programmes were followed for 1 year, to track their evolving definition of integration and the factors they felt were related to integra tion. The study also showed a general trend toward more positive evaluation over the year, and revealed that positive evaluation was frequently related to meeting new people and freedom from staff supervision. These findings are interpreted in the light of recommendations for community programmes.     

Effects of sertraline on brain current source of the high beta frequency band: analysis of electroencephalography during audiovisual erotic stimulation in males with premature ejaculation

To identify the effects of sertraline, a selective serotonin reuptake inhibitor, for the treatment of premature ejaculation (PE), changes in brain current-source density (CSD) of the high beta frequency band (22-30 Hz) induced by sertraline administration were investigated during audiovisual erotic stimulation. Eleven patients with PE (36.9±7.8 yrs) and 11 male volunteers (24.2±1.9 years) were enrolled. Scalp electroencephalography (EEG) was conducted twice: once before sertraline administration and then again 4 h after the administration of 50 mg sertraline. Statistical non-parametric maps were obtained using the EEG segments to detect the current-density differences in the high beta frequency bands (beta-3, 22-30 Hz) between the EEGs before and after sertraline administration in the patient group and between the patient group and controls after the administration of sertraline during the erotic video sessions. Comparing between before and after sertraline administration in the patients with PE, the CSD of the high beta frequency band at 4 h after sertraline administration increased significantly in both superior frontal gyri and the right medial frontal gyrus (P<0.01). The CSD of the beta-3 band of the patients with PE were less activated significantly in the middle and superior temporal gyrus, lingual and fusiform gyrus, inferior occipital gyrus and cuneus of the right cerebral hemisphere compared with the normal volunteers 4 h after sertraline administration (P<0.01). In conclusion, sertraline administration increased the CSD in both the superior frontal and right middle temporal gyrus in patients with PE. The results suggest that the increased neural activity in these particular cerebral regions after sertraline administration may be associated with inhibitory effects on ejaculation in patients with PE.     

The integration of colour and motion by the human visual brain

Objects in the visual scene are defined by different cues such as colour and motion. Through the integration of these cues the visual system is able to utilize different sources of information, thus enhancing its ability to discriminate objects from their backgrounds. In the following experiments, we investigate the neural mechanisms of cue integration in the human. We show, using functional magnetic resonance imaging (fMRI), that both colour and motion defined shapes activate the lateral occipital complex (LOC) and that shapes defined by both colour and motion simultaneously activate the anterior-ventral margins of this area more strongly than shapes defined by either cue alone. This suggests that colour and motion cues are integrated in the LOC and possibly a neighbouring, more anterior, region. We support this result using an fMR adaptation technique, demonstrating that a region of the LOC adapts on repeated presentations of a shape regardless of the cue that is used to define it and even if the cue is varied. This result raises the possibility that the LOC contains cue-invariant neurons that respond to shapes regardless of the cue that is used to define them. We propose that such neurons could integrate signals from different cues, making them more responsive to objects defined by more than one cue, thus increasing the ability of the observer to recognize them.     

On the extent and nature of nucleus-annulus integration

STUDY DESIGN.: Mechanical and microstructural assessment of nucleus-annulus integration. OBJECTIVE.: To investigate the existence of structural integration between the nucleus and the inner annulus. SUMMARY OF BACKGROUND DATA.: The nucleus is often viewed as a hydrostatically functioning entity that is largely separate from its surroundings. The boundary between nucleus and annulus is acknowledged as difficult to define. METHODS.: Ten-millimeter-thick sagittal slabs were cut from the central region of ovine lumbar discs. The annulus-nucleus transition region was isolated and the resulting samples subjected to transverse tensile loading up to failure. Similar samples were stretched to about 4 to 5 times their original separation and then subjected to microstructural examination to investigate structural integration across the inner annulus-nucleus region. RESULTS.: The annulus-nucleus boundary could support an average load of 5.7 N (range, 2-11.5 N). Tensile loading causes the fibrous structure of the nucleus to be drawn into an approximate alignment in the transverse stretch direction with an associated reverse inpulling of the inner annular layers. At high magnification, the horizontally aligned nucleus fibers can be seen to branch and blend with the inner annular structure. CONCLUSION.: The nucleus contains a convoluted but highly structured network of fibers of varying length, which appear to integrate with the inner annulus and confer a significant degree of transverse interconnectivity that can be demonstrated mechanically. This new experimental evidence, together with that from a previous study demonstrating nucleus-endplate connectivity, makes it clear that the nucleus cannot be considered as a separate entity in the disc. We propose that this structural integration provides the nucleus with a form of tethered mobility that supports physiological functions distinct from the primary strength requirements of the motion segment.     

Renal effect of anti-hypertensive drugs depends on sodium diet in the excision remnant kidney model.

Angiotensin converting enzyme inhibitors (ACEI) are believed to protect remnant kidney, but all previous studies used the ligation model which causes severe hypertension, and very few have compared drugs in rats having similar control of blood pressure (BP). We compared rats with uremia obtained by 70% excision of total renal mass, a model which causes mild, late hypertension. Study I compared the effects of enalapril (E), cicletanine (C) and placebo (P) in uremic (U) rats fed a 0.50% (normal-high) Na diet. Study II compared the effects of E, C, P, and guanfacine (G) in U rats fed a diet restricted to 0.25% Na (normal-low). In study I, UP rats developed progressive hypertension (140, 146, 160 and 166 mm Hg at 3, 6, 9 and 12 weeks), proteinuria (240 mg/day at 9 and 12 weeks) which were not affected by E or C. The occurrence of end-stage renal disease (ESRD) led to the sacrifice of all rats after three months. All three groups had similar severe renal lesions (over 25% sclerosed glomeruli in 5 of 10 UP, 9 of 14 UE, 7 of 14 UC rats, with huge cystic tubular dilatations). In study II, rats could be sacrificed later (6 months) and had evidence of less severe renal disease. All the drugs tested prevented hypertension throughout the study (P less than 0.001), with lowest values in UE rats. E and G, but not C, reduced proteinuria. Renal damage was reduced with E and G, but not with C, despite similar BP in C and G rats. Thus, in contrast with what was obtained in the ligation model, ACEI affected neither the BP nor the renal lesions of rats made uremic by renal excision and fed a 0.50% Na diet. Moderate Na restriction improved the consequences of nephron loss and restored the anti-hypertensive effect of drugs. However, these drugs had a different effect on renal preservation: it was dramatic with E, good with G, and undetectable with C.     

The effect of craniectomy on the biomechanics of normal brain

Does an open skull alter the fundamental biomechanical properties of normal brain tissue? This question was studied in 32 anesthetized cats, 16 of which underwent a standard craniectomy (2.5 X 2.0 cm) in the left frontoparietal region. Brain tissue pressure, regional cerebral blood flow (rCBF), and brain water content were measured from the same area of cortical gray and white matter, and intracranial pressure (ICP) was recorded from the cisterna magna. Brain tissue resistance, tissue compliance, and the pressure-volume index were analyzed in response to a bolus injection of saline into brain tissue or the cisterna magna. Cerebrovascular resistance was also calculated. In craniectomized animals 2 hours after surgery, ICP had fallen to 3.75 +/- 0.39 mm Hg, and cortical gray and white matter tissue pressure had fallen to 3.19 +/- 0.47 and 4.69 +/- 0.54 mm Hg, respectively (mean +/- standard error of the mean); these variables did not fall further over 4 hours. The pressure-volume index in the same animals increased significantly from 0.67 +/- 0.01 to 0.86 +/- 0.04 ml. Tissue compliance rose in the cortical gray matter but tissue resistance fell, approximating that found in subjacent white matter. There was no significant difference between animals with and without craniectomy in rCBF, cerebrovascular resistance, or brain water content in either gray or white matter. These findings indicate that in the cat craniectomy causes an increase in the compensatory capacity of the intracranial cavity to increased volume. The data also indicate that cortical tissue has high hydraulic conductivity and compliance when the skull is opened.