Cerebral oxygenation saturation in childhood: difference by age and comparison of two cerebral oximetry algorithms.

Few reports are available on the monitoring of regional cerebral oxygen saturation (rSO2) in pediatric patients undergoing non-cardiac surgical procedures. In addition, no study has examined the rSO2 levels in children of a broad age range. In this study, we aimed to assess and compare rSO2 levels in pediatric patients of different age groups undergoing non-cardiac surgery. We used two oximeters, tNIRS-1, which uses time-resolved spectroscopy, and conventional INVOS 5100C. Seventy-eight children-26 infants, 26 toddlers, and 26 schoolchildren-undergoing non-cardiac surgery were included. We investigated the differences in the rSO2 levels among the age groups and the correlation between the models and physiological factors influencing the rSO2 values. rSO2 measured by INVOS 5100C was significantly lower in infants than those in other patients. rSO2 measured by tNIRS-1 was higher in the toddler group than those in the other groups. The rSO2 values of tNIRS-1 and INVOS 5100C were moderately correlated (r = 0.41); however, those of INVOS 5100C were approximately 20% higher, and a ceiling effect was observed. The values in INVOS 5100C and tNIRS-1 were affected by blood pressure and the minimum alveolar concentration of sevoflurane, respectively. In pediatric patients undergoing non-cardiac surgery, rSO2 values differed across the three age groups, and the pattern of these differences varied between the two oximeters employing different algorithms. Further research must be conducted to clarify cerebral oxygenation in children.

Effects of ephedrine and phenylephrine on cerebral oxygenation: observational prospective study using near-infrared time-resolved spectroscopy.

It has been reported that cerebral oxygenation (ScO2) measured by near infrared spectroscopy is maintained or increased by treatment with ephedrine, whereas almost all previous reports demonstrated that phenylephrine reduced ScO2. As the mechanism of the latter, the interference of the extracranial blood flow, that is extracranial contamination, has been suspected. Accordingly, in this prospective observational study, we utilized time-resolved spectroscopy (TRS), in which the effect of extracranial contamination is thought to be minimal, and evaluated whether the same result was obtained. We measured the changes in ScO2 as well as the total cerebral hemoglobin concentration (tHb) after treatment with ephedrine or phenylephrine during laparoscopic surgery by using a tNIRS-1 (Hamamatsu Photonics, Hamamatsu, Japan), which is a commercial instrument utilizing TRS. Based on a mixed-effects model with random intercepts for ScO2 or tHb including mean blood pressure, the mean difference and 95% confidence interval were evaluated as well as the predicted mean difference and its confidence interval using the interquartile range of mean blood pressure. Fifty treatments with ephedrine or phenylephrine were done. The mean differences of ScO2 were less than 0.1% and the predicted mean differences were less than 1.1% for the two drugs. The mean differences of tHb were less than 0.02 µM and the predicted mean differences were less than 0.2 µM for the drugs. The changes in ScO2 and tHb after treatments with ephedrine and phenylephrine were very small and clinically insignificant when measured by TRS. Previous reports about phenylephrine may have been affected by extracranial contamination.

Differences of cerebral oxygen saturation in dialysis patients: a comparison of three principals of near infrared spectroscopy.

PURPOSE: It has been reported that cerebral oxygen saturation (rSO2) measured by near infrared spectroscopy is low in dialysis patients. We compared the rSO2 values of dialysis patients before living donor kidney transplantation and their donors as controls by using three spectroscopes that utilize different principals, the INVOS 5100C (spatially resolved spectroscopy), FORE-SIGHT ELITE (modified Beer-Lambert law) and tNIRS-1 (time-resolved spectroscopy). METHODS: Before induction of anesthesia, the sensors of one of the three spectroscopes were placed on the forehead and rSO2 values were recorded followed by the same measurement using the other two spectroscopes. The primary objective was to compare the rSO2 values of the dialysis patients and controls using the three spectroscopes by the unpaired t test. Then we compared the rSO2 values among the spectroscopes in both dialysis patients and controls by one-way ANOVA. Finally, we examined the relations between the rSO2 values and the physiological values by using the Pearson correlation coefficient. RESULTS: Fifteen pairs of dialysis patients and controls were studied. With the INVOS 5100 C, the values of the dialysis patients (59.7 ± 9.7% (mean ± standard deviation) were 13% lower than those of the controls (73.3 ± 6.9%) (P < 0.01). With the tNIRS-1, the values were 57.8 ± 4.8% in the dialysis patients and 63.3 ± 3.5% in the controls (P < 0.01). Almost no differences were observed with the FORE-SIGHT ELITE (71.6 ± 4.9% [dialysis patients] vs. 70.8 ± 4.3% [Controls]) (P = 0.62). Among the spectroscopes, the values were significantly different in both dialysis patients and controls. For the INVOS 5100C and tNIRS-1, correlation coefficients between rSO2 values and blood Hb and serum Alb were more than 0.5. CONCLUSIONS: The rSO2 values for comparisons between the dialysis patients and the controls were different according to differences of the principles of the near infrared spectroscopes. In the INVOS 5100C and tNIRS-1, rSO2 values may be related to blood Hb and serum Alb.

Age Difference of the Relationship Between Cerebral Oxygen Saturation and Physiological Parameters in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: Analysis Using the Random-Effects Model.

Recently, monitoring of cerebral oxygen saturation (ScO2) has become widespread in pediatric cardiac surgery. Our previous study reported that mean blood pressure (mBP) was the major contributor to ScO2 throughout cardiac surgery with cardiopulmonary bypass (CPB) in children weighing under 10 kg. We speculated that this result might be attributable to incomplete cerebral autoregulation in such young children. Accordingly, our hypothesis is that the relationship between ScO2 and the physiological parameters may change according to the growth of the children. ScO2 was measured with an INVOS 5100C (Somanetics, Troy, MI). Random-effects analysis was employed with ScO2 as a dependent variable, and seven physiological parameters (mBP, central venous pressure, nasopharyngeal temperature, SaO2, hematocrit, PaCO2, and pH) were entered as independent covariates. The analysis was performed during the pre-CPB, CPB, and post-CPB periods by dividing the patients into two groups: infants (Infant Group) and children who were more than 1 year old (Child Group). The Infant and Child Groups consisted of 28 and 21 patients. In the random-effects analysis, mBP was the major contributor to ScO2 during CPB in both groups. During the pre-CPB period, the effect of mBP was strongest in the Infant group. However, its effect was second to that of SaO2 in the Child Group. During the post-CPB period, SaO2 and mBP still affected ScO2 in the Infant group. However, the dominant contributors were unclear in the Child Group. Cerebral autoregulation may be immature in infants. In addition, it may be impaired during CPB even after 1 year of age.

Changes of cerebral oxygenation indices measured by near infrared time-resolved spectroscopy during spinal anesthesia for cesarean section: Simultaneous measurement with cerebral blood flow.

AIM: To measure the changes in cerebral oxygenation indices by near infrared time-resolved spectroscopy and the cerebral blood flow simultaneously after spinal anesthesia for cesarean section. METHODS: This prospective observational study was conducted for 25 pregnant women scheduled for elective cesarean section under spinal anesthesia. During a period of 15 min after spinal anesthesia, cerebral oxygenation (ScO2 ), and the total cerebral hemoglobin concentration (tHb) were measured using near infrared time-resolved spectroscopy and mean cerebral blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography. Next, in the women who had nausea during the observed period, we compared these values when nausea was detected with those when it was not. RESULTS: Mean arterial pressure (MAP) decreased to around 60 mmHg (by 25% compared to the control) 6 min after spinal anesthesia. Compared to the control, ScO2 decreased by about 3% after 6 min and then gradually increased. The tHb, which reflects cerebral blood volume started to decrease just after spinal anesthesia and this continued until 12 min (the decrease was about 12%). Vm decreased by about 7%. In the 14 women who had nausea, MAP, Vm, and ScO2 values when nausea was detected were significantly lower than when it was not. CONCLUSION: The changes in cerebral hemodynamics may be small after spinal anesthesia in ordinary cesarean section compared to the reduction of systemic arterial blood pressure. There might be greater decreases in cerebral blood flow and oxygenation when nausea occurred in the pregnant women who experienced it after spinal anesthesia.

The Relationships of Cerebral and Somatic Oxygen Saturation with Physiological Parameters in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: Analysis Using the Random-Effects Model.

Recently, tissue oxygenation in pediatric heart surgery is measured by using near-infrared spectroscopy. Monitoring of cerebral oxygen saturation (ScO2) is most common but that of somatic tissue oxygen saturation (SrO2) is also gradually becoming widespread. However, the value of their monitoring is not well established. One of the reasons for this may be that the physiological factors affecting ScO2 and SrO2 have not been sufficiently clarified. Accordingly, we prospectively observed the changes in ScO2 and SrO2 simultaneously throughout cardiac surgery with cardiopulmonary bypass (CPB) in children weighing under 10 kg and evaluated their relationships with physiological parameters by using the random-effects model. ScO2 and SrO2 were measured with an INVOS 5100C (Somanetics, Troy, MI, USA). The random-effects analysis was applied for ScO2 and SrO2, as dependent variables, and seven physiological parameters (mean blood pressure, central venous pressure, rectal temperature, SaO2, hematocrit PaCO2, and pH) were entered as independent covariates. The analysis was performed during the pre-CPB, CPB, and post-CPB periods. Next, the same analysis was performed by dividing the patients into univentricular and biventricular physiological types. Forty-one children were evaluated. Through the whole surgical period, ScO2 correlated strongly with mean blood pressure regardless of the physiological type. On the other hand, the contribution of mean blood pressure to SrO2 was weak and various other parameters were related to SrO2 changes. Thus, the physiological parameters affecting ScO2 and SrO2 were rather different. Accordingly, the significance of monitoring of cerebral and somatic tissue oxygen saturation in pediatric cardiac surgery should be further evaluated.

Facilitation of fear extinction by the 5-HT(1A) receptor agonist tandospirone: possible involvement of dopaminergic modulation.

Fear extinction-based exposure treatment is an important component of psychotherapy for anxiety disorders such as posttraumatic stress disorder (PTSD). Recent studies have focused on pharmacological approaches combined with exposure therapy to augment extinction. In this study, we elucidated the therapeutic potential of the serotonin 1A (5-HT(1A) ) receptor agonist tandospirone compared with the effects of the N-methyl-D-aspartate partial agonist D-cycloserine (DCS), focusing on the possible involvement of dopaminergic mechanisms. We used a rat model of juvenile stress [aversive footshock (FS)] exposure during the third postnatal week (3wFS). The 3wFS group exhibited extinction deficit reflected in sustained fear-related behavior and synaptic dysfunction in the hippocampal CA1 field and medial prefrontal cortex (mPFC), which are responsible for extinction processes. Tandospirone administration (5 mg/kg, i.p.) before and after the extinction trials ameliorated both the behavioral deficit and synaptic dysfunction, i.e., synaptic efficacy in the CA1 field and mPFC associated with extinction training and retrieval, respectively, was potentiated in the tandospirone-treated 3wFS group. Extracellular dopamine release in the mPFC was increased by extinction retrieval in the non-FS control group. This facilitation was not observed in the 3wFS group; however, tandospirone treatment increased cortical dopamine levels after extinction retrieval. DCS (15 mg/kg, i.p.) also ameliorated the extinction deficit in the 3wFS group, but impaired extinction in the non-FS control group. These results suggest that tandospirone has therapeutic potential for enhancing synaptic efficacy associated with extinction processes by involving dopaminergic mechanisms. Pharmacological agents that target cortical dopaminergic systems may provide new insights into the development of therapeutic treatments of anxiety disorders, including PTSD.

Enhanced depressive-like behaviors after Toll-like receptor 7 stimulation in mice.

Toll-like receptor (TLR) 7 recognizes viral single-stranded RNA and triggers anti-viral immune responses through the production of type I interferons (IFNs) IFN-alpha and IFN-beta. IFN-alpha is known to induce various psychiatric changes such as depressive symptoms; however, the correlation with TLR7 activation remains to be determined. In this study, we examined the effect of imiquimod, a TLR7 specific ligand, on depressive-like behaviors evaluated by the forced swim test (FST) and the tail suspension test (TST) in mice. Immobility durations were significantly prolonged in both FST and TST by 2 h after imiquimod treatment (50 microg/body, i.p.), indicating that TLR7 activation enhanced depressive-like behaviors in mice. In addition, imiquimod induced IFN-alpha mRNA expression in the hippocampus, whereas it prevented long-term potentiation in the Schaffer-CA1 pathway (i.e., hippocampal synaptic plasticity). Moreover, TLR7 mRNA expression in the hippocampus was higher than that in the whole brain. These findings suggest that TLR7 activation enhances depressive-like behaviors in mice, possibly through increasing IFN-alpha expression and altering synaptic plasticity in the hippocampus.

Possible modulation of the amygdala on metaplasticity deficits in the hippocampal CA1 field in early postnatally stressed rats.

Several lines of evidence have shown that early life experiences have a profound impact on fear-related behavior, but the detailed mechanisms are unknown. The present study examined the possible involvement of the amygdala in behavioral deficits associated with fear memory in a juvenile stress model, with a focus on hippocampal synaptic function. Adult rats exposed to footshock (FS) stress during the second postnatal period (2wFS group) exhibited low levels of freezing in response to contextual fear conditioning (CFC). The CFC-induced suppression of long-term potentiation (LTP) in the CA1 field was not found in the 2wFS group. Additionally, synaptic metaplasticity, that is, low-frequency stimulation-induced suppression of subsequent LTP, did not occur in the 2wFS group; instead, LTP was induced. These synaptic changes mimicked the impairment in metaplasticity induced by reversible inactivation of the basolateral amygdala (BLA). Inactivation of the BLA markedly decreased freezing behavior in non-FS controls, similar to the 2wFS group. Furthermore, extracellular signal-regulated kinase activation in the BLA in response to CFC did not occur in the 2wFS group. These findings suggest that early postnatal stress may cause long-term dysfunction of the modulatory effect of the amygdala on hippocampal function associated with fear memory.

[A case of portal vein thrombosis complicating acute cholangitis treated successfully with danaparoid sodium].

An 81-year-old woman was referred to our hospital with a diagnosis of acute cholangitis. Endoscopic retrograde cholangiography revealed a common bile duct (CBD) stone. In addition, CT showed thrombus of the right portal vein. Endoscopic sphincterotomy was performed to remove the CBD stone. Thrombosis was treated successfully with danaparoid sodium. It was speculated that the treatment of the acute cholangitis induced thrombolysis by the auto-fibrinolysis system and danaparoid sodium prevented the development of thrombus formation in this case.

Effects of serotonergic terminal lesion in the amygdala on conditioned fear and innate fear in rats.

The amygdala and the medial prefrontal cortex (mPFC) are crucial brain structures for anxiety, and it is speculated that the serotonergic neural system in these structures has an important role in regulating anxiety. In our previous study, we indicated that local injections of selective serotonin reuptake inhibitor into the amygdala attenuated anxiety-related behaviors in conditioned fear in rats. In the present study, we investigated the effects of serotonergic terminal lesions in the amygdala and in mPFC induced by local injection of 5,7-dihydroxytryptamine (5,7-DHT), on anxiety-related behaviors in conditioned fear and the elevated plus-maze test in rats. A 5,7-DHT lesion in the amygdala attenuated memory-dependent fear assessed by conditioned fear, but enhanced memory-independent fear assessed by the elevated plus-maze test. These results suggest that the role of the amygdalar serotonergic system in fear is different between memory-dependent and independent fear and, in particular, it is paradoxical that an amygdalar serotonergic lesion exerts a similar effect on memory-dependent fear to SSRI. Moreover, a serotonergic lesion in the amygdala enhanced the retrieval of extinction memory in conditioned fear; however, a serotonergic lesion in mPFC did not bring about any behavioral changes.

Toll-like receptor 7-mediated enhancement of contextual fear memory in mice.

Toll-like receptor (TLR) 7 recognizes viral single-stranded RNA and triggers production of the type I interferons (IFNs) IFN-α and IFN-ß. Imiquimod, a synthetic TLR7 ligand, induces production of type I IFNs and is used clinically as an antiviral and antitumor drug. In the present study, we examined the effect of imiquimod on conditioned and innate fear behaviors in mice. Imiquimod was administered 2, 4, or 15 h before contextual fear conditioning. Imiquimod treatment 4 or 15 h before fear conditioning significantly enhanced context-dependent freezing behavior. This imiquimod-induced enhancement of fear-related behaviors was observed 120 h after fear conditioning. In contrast, imiquimod failed to enhance context-dependent freezing behavior in TLR7 knockout mice. Imiquimod had no significant effect on pain threshold or on innate fear-related behavior, as measured by the elevated plus-maze. The levels of type I IFN mRNA in the brain were significantly increased at 2 h after imiquimod treatment. Imiquimod also increased interleukin (IL)-1ß mRNA expression in the brain at 4 h following administration, while mRNA expression of F4/80, a macrophage marker, was unaffected by imiquimod treatment. Our findings suggest that TLR7-mediated signaling enhances contextual fear memory in mice, possibly by inducing the expression of type I IFNs and IL-1ß in the brain.

A case of polyarteritis nodosa complicated by rectal cancer.

Solid cancers are rarely complicated by the occurrence of polyarteritis nodosa (PN), and most cases diagnosed as PN are, in fact, cases of paraneoplastic vasculitis. Paraneoplastic vasculitis is usually resolved after tumor removal. We present a rare case of a 69-year-old man with PN complicated by rectal cancer, without the occurrence of paraneoplastic vasculitis. Microscopic examination of the resected cancer lesion revealed inflammation of some arteries and neutrophil and lymphocyte infiltration, fibrin deposition, stenosis, and vasodilatation of capillaries caused by congestion in the submucosal layer. It was unclear how these findings exerted influence on the rectal cancer. Although the symptoms of PN did not improve after the patient's tumor was removed surgically, the symptoms improved rapidly after oral treatment with prednisolone and cyclophosphamide.