Internal Jugular Venous Blood Research Articles

Cerebral venous biomarkers and veno-arterial gradients: untapped resources in Alzheimer's disease.

Blood based biomarkers (BBB) derived from forearm veins for estimating brain changes is becoming ubiquitous in Alzheimer's Disease (AD) research and could soon become standard in routine clinical diagnosis. However, there are many peripheral sources of contamination through which concentrations of these metabolites can be raised or lowered after leaving the brain and entering the central venous pool. This raises the issue of potential false conclusions that could lead to erroneous diagnosis or research findings. We propose the use of simultaneous sampling of internal jugular venous and arterial blood to calculate veno-arterial gradient, which can reveal either a surplus or a deficit of metabolites exiting the brain. Methods for sampling internal jugular venous and arterial blood are described along with examples of the use of the veno-arterial gradient in non-AD brain research. Such methods in turn could help better establish the accuracy of forearm venous biomarkers.

One-lung ventilation patients: Clinical context of administration of different doses of dexmedetomidine.

BackgroundOpen and endoscopic thoracic surgeries improve surgical exposure by One-lung ventilation (OLV). The aim of this study was to investigate the effects of different doses of dexmedetomidine on inflammatory response, oxidative stress, cerebral tissue oxygen saturation (SctO2) and intrapulmonary shunt in patients undergoing one-lung ventilation (OLV).MethodsSeventy-five patients undergoing open pulmonary lobectomy in our hospital from January 2016 to December 2017 were enrolled and randomly divided into high-dose dexmedetomidine group (group D1, 1 mg/kg, n=25), low-dose dexmedetomidine group (group D2, 0.5 mg/kg, n=25) and control group (group C, n=25). Then, arterial blood and internal jugular venous blood were taken before anesthesia induction (T0) and at 15 min after twolung ventilation (T1) and 5 min (T2) and 30 min (T3) after OLV for later use. Next, the changes in hemodynamic parameters [mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2)] of patients were observed in each group. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect serum inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)]. The changes in SctO2, arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt Qs/Qt (a measurement of pulmonary shunt: right-to-left shunt fraction) were observed. Additionally, the changes in lung function indicators like lung dynamic compliance (Cdyn) and airway peak pressure (Ppeak) were determined.ResultsThere were no statistically significant differences in the MAP, HR and SpO2 among three groups at each observation time point (P>0.05). At T2 and T3, the levels of serum IL-6, TNF-α and IL-8 were obviously decreased in group D1 and D2 compared with those in group C (P<0.05), and the decreases in group D1 were overtly larger than those in group D2, and the decreases at T3 were markedly greater than those at T2 (P<0.05). In comparison with group C, group D1 and D2 had notably reduced levels of serum reactive oxygen species (ROS) and MDA (P<0.05) and remarkably increased SOD content (P<0.05) at T2 and T3, and the effects were markedly better in group D1 than those in group D2. Besides, they were significantly superior at T3 to those at T2 (P<0.05). The SctO2 in group D1 and D2 was evidently lowered at T2 and T3 compared with that at T0, and the decrease in group D1 was distinctly smaller than that in group D2 (P<0.05). The Qs/Qt was significantly lower in group D1 and D2 than that in group C at T2 and T3 (P<0.05), while the PaO2 content was notably raised (P<0.05), and the decrease and increase were significantly larger in group D1 than those in group D2, and they were obviously greater at T3 to those at T2 (P<0.05). At T0 and T1, no significant differences were detected in the Cdyn, Pplat and Ppeak among three groups. At T2 and T3, the Cdyn was significantly elevated, while the Pplat and Ppeak overtly declined (P<0.05), and group D1 had greater changes in comparison with group D2, and the changes were obviously more evident at T3 to those at T2 (P<0.05).ConclusionsDexmedetomidine effectively ameliorates inflammatory response and oxidative stress, lowers oxygenation, Qs/Qt and the decrease in SctO2 and improves lung function during OLV, with good efficacy.

Hypoxia ameliorates brain hyperoxia and NAD+ deficiency in a murine model of Leigh syndrome

Leigh syndrome is a severe mitochondrial neurodegenerative disease with no effective treatment. In the Ndufs4−/− mouse model of Leigh syndrome, continuously breathing 11% O2 (hypoxia) prevents neurodegeneration and leads to a dramatic extension (~5-fold) in lifespan. We investigated the effect of hypoxia on the brain metabolism of Ndufs4−/− mice by studying blood gas tensions and metabolite levels in simultaneously sampled arterial and cerebral internal jugular venous (IJV) blood. Relatively healthy Ndufs4−/− and wildtype (WT) mice breathing air until postnatal age ~38 d were compared to Ndufs4−/− and WT mice breathing air until ~38 days old followed by 4-weeks of breathing 11% O2. Compared to WT control mice, Ndufs4−/− mice breathing air have reduced brain O2 consumption as evidenced by an elevated partial pressure of O2 in IJV blood (PijvO2) despite a normal PO2 in arterial blood, and higher lactate/pyruvate (L/P) ratios in IJV plasma revealed by metabolic profiling. In Ndufs4−/− mice, hypoxia treatment normalized the cerebral venous PijvO2 and L/P ratios, and decreased levels of nicotinate in IJV plasma. Brain concentrations of nicotinamide adenine dinucleotide (NAD+) were lower in Ndufs4−/− mice breathing air than in WT mice, but preserved at WT levels with hypoxia treatment. Although mild hypoxia (17% O2) has been shown to be an ineffective therapy for Ndufs4−/− mice, we find that when combined with nicotinic acid supplementation it provides a modest improvement in neurodegeneration and lifespan. Therapies targeting both brain hyperoxia and NAD+ deficiency may hold promise for treating Leigh syndrome.

Nitric oxide is fundamental to neurovascular coupling in humans.

Preclinical models have demonstrated that nitric oxide is a key component of neurovascular coupling; this has yet to be translated to humans. We conducted two separate protocols utilizing intravenous infusion of a nitric oxide synthase inhibitor and isovolumic haemodilution to assess the influence of nitric oxide on neurovascular coupling in humans. Isovolumic haemodilution did not alter neurovascular coupling. Intravenous infusion of a nitric oxide synthase inhibitor reduced the neurovascular coupling response by ∼30%, indicating that nitric oxide is integral to neurovascular coupling in humans. Nitric oxide is a vital neurovascular signalling molecule in preclinical models, yet the mechanisms underlying neurovascular coupling (NVC) in humans have yet to be elucidated. To investigate the contribution of nitric oxide to NVC in humans, we utilized a visual stimulus paradigm to elicit an NVC response in the posterior cerebral circulation. Two distinct mechanistic interventions were conducted on young healthy males: (1) NVC was assessed during intravenous infusion of saline (placebo) and the non-selective competitive nitric oxide synthase inhibitor NG -monomethyl-l-arginine (l-NMMA, 5 mg kg-1 bolus & subsequent 50 μg kg-1 min-1 maintenance dose; n = 10). The order of infusion was randomized, counterbalanced and single blinded. A subset of participants in this study (n = 4) underwent a separate intervention with phenylephrine infusion to independently consider the influence of blood pressure changes on NVC (0.1-0.6 μg kg-1 min-1 constant infusion). (2) NVC was assessed prior to and following isovolumic haemodilution, whereby 20% of whole blood was removed and replaced with 5% human serum albumin to reduce haemoglobin concentration (n = 8). For both protocols, arterial and internal jugular venous blood samples were collected at rest and coupled with volumetric measures of cerebral blood flow (duplex ultrasound) to quantify resting cerebral metabolic parameters. l-NMMA elicited a 30% reduction in the peak (P = 0.01), but not average (P = 0.11), NVC response. Neither phenylephrine nor haemodilution influenced NVC. Nitric oxide signalling is integral to NVC in humans, providing a new direction for research into pharmacological treatment of humans with dementia.

Study of multimodal monitoring in neurocritical care patients

To explore the significance of multimodal monitoring in the monitoring and treatment of neurocritical care patients. 104 neurocritical care patients admitted to the department of Critical Care Medicine of Fujian Provincial Hospital from March 2019 to January 2020 were enrolled. Patients were randomly assigned into two groups, with 52 in each group. In the routine monitoring treatment group, heart rate, blood pressure, respiratory rate and the changes in consciousness and pupils were monitored after operation. The patients were treated with routine medicine to reduce intracranial pressure (ICP), maintain proper cerebral perfusion pressure (CPP), balance fluid intake and output, and maintain the airway clear. Patients in the multimodal monitoring treatment group were treated with invasive ICP monitoring, ultrasound to assess brain structure, ultrasound to measure optic nerve sheath diameter (ONSD), transcranial color doppler (TCCD), internal jugular venous blood oxygen saturation monitoring, near-infrared spectroscopy (NIRS), non-invasive cerebral blood oxygen saturation monitoring and quantitative electroencephalogram monitoring. According to the monitoring results, the patients were given targeted treatment with the goal of controlling ICP and improving brain metabolism. The length of intensive care unit (ICU) stay, the incidences of neurological complications (secondary cerebral infarction, cerebral hemorrhage, high intracranial pressure, etc.), and the incidences of poor prognosis [6 months after the onset of Glasgow outcome score (GOS) 1 to 3] were compared between the two groups. Spearman rank correlation analysis of the correlation between invasive ICP and the ICP value which was calculated by TCCD. The receiver operating characteristic (ROC) curve of invasive ICP and pulsatility index of middle cerebral artery (PIMCA) were used to predict poor prognosis. The length of ICU stay in the multimodal monitoring treatment group was significantly shorter than that of the routine monitoring treatment group (days: 6.27±3.81 vs. 9.61±5.09, P < 0.01), and the incidence of neurological complications was significantly lower than that in the routine monitoring treatment group (9.62% vs. 25.00%, P < 0.05). In the multimodal monitoring treatment group, 37 cases had a good prognosis and 15 cases had a poor prognosis, while the routine monitoring treatment group had a good prognosis in 27 cases and a poor prognosis in 25 cases. The incidence of poor prognosis in the multimodal monitoring treatment group was lower than that of the routine monitoring treatment group (28.85% vs. 48.08%, P < 0.05). In the multimodal monitoring treatment group, the invasive ICP and PIMCA of patients with good prognosis were significantly lower than those of patients with poor prognosis [invasive ICP (mmHg, 1 mmHg = 0.133 kPa): 16 (12, 17) vs. 22 (20, 24), PIMCA: 0.90±0.33 vs. 1.39±0.58, both P < 0.01]. There was no significant difference in resistance index of the middle cerebral artery (RIMCA) between the good prognosis group and the poor prognosis group (0.63±0.12 vs. 0.66±0.15, P > 0.05). There was a positive correlation between the invasive ICP and the ICP value which was calculated by TCCD (r = 0.767, P < 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of invasive ICP for poor prognosis prediction was 0.906, the best cut-off value was ≥ 18 mmHg, the sensitivity was 86.49%, and the specificity was 86.67%. The AUC of PIMCA for poor prognosis prediction was 0.759, the best cut-off value was ≥ 1.12, the sensitivity was 81.08%, and the specificity was 60.00%. The AUC of invasive ICP was greater than PIMCA (Z = 2.279, P = 0.023). Comprehensive analysis of multimodal monitoring indicators for neurocritical care patients to guide clinical treatment can reduce the length of hospital stay, and reduce the risk of neurosurgery complications and disability; invasive ICP can predict poor prognosis of neurocritical care patients.

Human brain blood flow and metabolism during isocapnic hyperoxia: the role of reactive oxygen species.

It is unknown whether excessive reactive oxygen species (ROS) production drives the isocapnic hyperoxia (IH)-induced decline in human cerebral blood flow (CBF) via reduced nitric oxide (NO) bioavailability and leads to disruption of the blood-brain barrier (BBB) or neural-parenchymal damage. Cerebral metabolic rate for oxygen (CMR ) and transcerebral exchanges of NO end-products, oxidants, antioxidants and neural-parenchymal damage markers were simultaneously quantified under IH with intravenous saline and ascorbic acid infusion. CBF and were reduced during IH, responses that were followed by increased oxidative stress and reduced NO bioavailability when saline was infused. No indication of neural-parenchymal damage or disruption of the BBB was observed during IH. Antioxidant defences were increased during ascorbic acid infusion, while CBF, , oxidant and NO bioavailability markers remained unchanged. ROS play a role in the regulation of CBF and metabolism during IH without evidence of BBB disruption or neural-parenchymal damage. To test the hypothesis that isocapnic hyperoxia (IH) affects cerebral blood flow (CBF) and metabolism through exaggerated reactive oxygen species (ROS) production, reduced nitric oxide (NO) bioavailability, disturbances in the blood-brain barrier (BBB) and neural-parenchymal homeostasis, 10 men (24± 1years) were exposed to a 10min IH trial (100% O2 ) while receiving intravenous saline and ascorbic acid (AA, 3 g) infusion. Internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF) and total CBF (tCBF, Doppler ultrasound) were determined. Arterial and right internal jugular venous blood was sampled to quantify the cerebral metabolic rate of oxygen (CMR ), transcerebral exchanges (TCE) of NO end-products (plasma nitrite), antioxidants (AA and AA plus dehydroascorbic acid (AA+DA)) and oxidant biomarkers (thiobarbituric acid-reactive substances (TBARS) and 8-isoprostane), and an index of BBB disruption and neuronal-parenchymal damage (neuron-specific enolase; NSE). IH reduced ICABF, tCBF and , while VABF remained unchanged. Arterial 8-isoprostane and nitrite TCE increased, indicating that CBF decline was related to ROS production and reduced NO bioavailability. AA, AA+DA and NSE TCE did not change during IH. AA infusion did not change the resting haemodynamic and metabolic parameters but raised antioxidant defences, as indicated by increased AA/AA+DA concentrations. Negative AA+DA TCE, unchanged nitrite, reductions in arterial and venous 8-isoprostane, and TBARS TCE indicated that AA infusion effectively inhibited ROS production and preserved NO bioavailability. Similarly, AA infusion prevented IH-induced decline in regional and total CBF and re-established . These findings indicate that ROS play a role in CBF regulation and metabolism during IH without evidence of BBB disruption or neural-parenchymal damage.

A validation method for near-infrared spectroscopy based tissue oximeters for cerebral and somatic tissue oxygen saturation measurements

We describe the validation methodology for the NIRS based FORE-SIGHT ELITE® (CAS Medical Systems, Inc., Branford, CT, USA) tissue oximeter for cerebral and somatic tissue oxygen saturation (StO2) measurements for adult subjects submitted to the United States Food and Drug Administration (FDA) to obtain clearance for clinical use. This validation methodology evolved from a history of NIRS validations in the literature and FDA recommended use of Deming regression and bootstrapping statistical validation methods. For cerebral validation, forehead cerebral StO2 measurements were compared to a weighted 70:30 reference (REF CXB) of co-oximeter internal jugular venous and arterial blood saturation of healthy adult subjects during a controlled hypoxia sequence, with a sensor placed on the forehead. For somatic validation, somatic StO2 measurements were compared to a weighted 70:30 reference (REF CXS) of co-oximetry central venous and arterial saturation values following a similar protocol, with sensors place on the flank, quadriceps muscle, and calf muscle. With informed consent, 25 subjects successfully completed the cerebral validation study. The bias and precision (1 SD) of cerebral StO2 compared to REF CXB was −0.14 ± 3.07%. With informed consent, 24 subjects successfully completed the somatic validation study. The bias and precision of somatic StO2 compared to REF CXS was 0.04 ± 4.22% from the average of flank, quadriceps, and calf StO2 measurements to best represent the global whole body REF CXS. The NIRS validation methods presented potentially provide a reliable means to test NIRS monitors and qualify them for clinical use.

Thermodilution-determined Internal Jugular Venous Flow.

Cerebral blood flow (CBF) increases ~20% during whole body exercise although a Kety-Schmidt-determined CBF is reported to remain stable; a discrepancy that could reflect evaluation of arterial vs. internal jugular venous (IJV) flow and/or that CBF is influenced by posture. Here we test the hypothesis that IJV flow, as determined by retrograde thermodilution increases during exercise when body position is maintained. Introducing retrograde thermodilution, IJV flow was measured in eight healthy humans at supine and upright rest and during exercise in normoxia and hypoxia with results compared with changes in ultrasound-derived IJV flow and middle cerebral artery mean velocity (MCA Vmean). Thermodilution determined IJV flow was in reasonable agreement with values established in a phantom (R = 0.59, P < 0.0001) and correlated to the ultrasound-derived IJV flow (n = 7; Kendall τ, 0.28; P = 0.036). When subjects stood up, IJV blood flow decreased by 9% ± 13% (mean ± SD) (219 ± 57 to 191 ± 73 mL·min; P < 0.0001) and the influence of body position was maintained during exercise (P < 0.0001). Exercise increased both IJV flow and MCA Vmean (P = 0.019 and P = 0.012, respectively) and the two responses were similar (P = 0.50). During hypoxia, however, only MCA Vmean responded with a further increase (P < 0.0001). As determined by retrograde thermodilution, IJV flow seems little sensitive to hypoxia, but does demonstrate the about 15% reduction in CBF when humans are upright and, provided that body position is maintained, also the increase in CBF during whole body exercise.

Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 .

Effects of low level of positive end expiratory pressure on cerebral hemodynamics in patient undergoing laparo-scopic radical gastrostomy with general anesthesia

Objective To observe the effects of low levels of positive end expiratory pressure on cerebral hemodynamics in patients with gastric cancer undergoing laparoscopic radical resection surgery under general anesthesia. Methods 80 patients(ASAⅠ-Ⅱ), scheduled to undergo laparoscopic radical gastrostomy, were randomly divided into group A, and group B, each group had 40 cases. The ventilation parameters of group A:tidal volume(VT): 8 ml/kg, respiratory rate(RR): 12 min, positive end expiratory pressure (PEEP):5 cm H2 O(1 cm H2 O= 0.098 kPa). Group B was:VT:8 ml/kg, RR:12 min.Recording the average blood flow velocity in the middle cerebral artery(Vm),mean arterial pressure(MAP),heart rate(HR), transcutaneous oxygen saturation(SpO2),end-tidal carbon dioxide pressure(PetCO2)of the two group before pneumoperitoneum(T0),30 min after pneumoperitoneum(T1), 1 hours(T2)and 2 hours(T3)after pneumoperitoneum. Blood samples of jugular bulb and radial artery were obtained at each time point for blood gas analysis, detection the arterial oxygen pressure(PaO2), arterial carbon dioxide pressure(PaCO2), arterial oxygen saturation(SaO2), hemoglobin concentration(Hb), internal jugular venous blood oxygen partial pressure(PjvO2), internal jugular venous oxygen saturation(SjvO2), jugular venous oxygen content(CjvO2), and arterial-jugular venous oxygen content difference(Da-jvO2). Results Compared with T0,the Vm,SjvO2, PaCO2 of the two groups increased significantly at each time point(P<0.05).But the Vm, SjvO2 of group A at T2 was significantly lower than that in group B(P<0.05),and the PaCO2 of group A at T1 and T2 were(35.5±2.7),(40.7±3.5)mm Hg respectively, which significantly lower than that of group B [(39.9±3.1),(49.4±4.7)mm Hg,P<0.05].And the Vm of group A at T2 was(68.9±8.1)cm/s,significantly lower than that of group B(P<0.05).Compared with T0, the Da- jvO2 at T2 of two groups decreased significantly(P<0.05),and between the two groups, A group decreased significantly than that in B group(P<0.05). Conclusion The low level of positive end expiratory pressure in patients undergoing laparoscopic radical gastrostomy with general anesthesia can effectively reduce the hypercapnia during operation, and improve cerebral hyperperfusion state,so as to improve the cerebral blood flow and improve cerebral oxygen supply and demand balance. Key words: Positive end expiratory pressure; Laparoscopy; Radical gastrectomy; Cerebral hemodynamics

Hydroperoxide in Internal Jugular Venous Blood Reflects Occurrence of Subarachnoid Hemorrhage-Induced Delayed Cerebral Vasospasm

To investigate the association between subarachnoid hemorrhage-induced delayed cerebral vasospasm (DCVS) and oxidative stress, an oxidation product, hydroperoxide, was measured in 3 specimens: peripheral arterial blood, cerebrospinal fluid (CSF), and internal jugular venous blood (IJVB). Hydroperoxide was measured using the diacron reactive oxygen metabolites (d-ROMs) test. The hydroperoxide levels were evaluated based on the rate of change in the d-ROMs test value on day 6 relative with that on day 3 (d-ROMs change rate). The subjects were 20 patients. The d-ROMs change rate in IJVB was significantly higher in patients with DCVS on day 6 than in those without it (P < .01). When the patients were classified into the following 3 groups: Group A (no DCVS occurred throughout the clinical course); Group B (DCVS occurred, but no cerebral infarction [CI] was induced); and Group C (DCVS occurred and caused CI), the d-ROMs change rate in IJVB was the highest in Group C, followed by Group B then A (P < .01). The d-ROMs change rates in peripheral arterial blood and CSF were not related to the development of DCVS. It was concluded that the more severe DCVS occurs and is more likely to progress to CI as the IJVB hydroperoxide level rises early after the development of subarachnoid hemorrhage.

Influence of intranasal and carotid cooling on cerebral temperature balance and oxygenation

The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood temperatures were measured to assess the cerebral heat balance and corresponding paired blood samples were obtained to evaluate cerebral metabolism and oxygenation at rest, following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min with carotid cooling. Intranasal cooling induced a parallel drop in jugular venous and arterial blood temperatures by 0.30 ± 0.08°C (mean ± SD), whereas nasal ventilation and carotid cooling failed to lower the jugular venous blood temperature. The magnitude of the arterio-venous temperature difference across the brain remained unchanged at −0.33 ± 0.05°C following intranasal and carotid cooling, but increased to −0.44 ± 0.11°C (P < 0.05) following nasal ventilation. Calculated cerebral capillary oxygen tension was 43 ± 3 mmHg at rest and remained unchanged during intranasal and carotid cooling, but decreased to 38 ± 2 mmHg (P < 0.05) following increased nasal ventilation. In conclusion, percutaneous cooling of the carotid arteries and intranasal cooling with balloon catheters are insufficient to influence cerebral oxygenation in normothermic subjects as the cooling rate is only 0.3°C per hour and neither intranasal nor carotid cooling is capable of inducing selective brain cooling.

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Introduction: Recently, ILCOR and AHA have been recommended to treat patients, who returned spontaneous circulation (ROSC) from cardiac arrest, by therapeutic hypothermia. Recently, we have tried to examine predictors, such as internal jugular venous blood oxygen saturation (SjvO2), glucagon, glucose, glial fibrillary acidic protein, procalcitonin, interleukin-8, interleutin-6, S100B and high morbidity group box 1 in serum and/or cerebrospinal fluid (CSF) within 48 hours after ROSC. But those values could not be got within a few hours except for SjvO2. Therefore, we need a predictor to detect the outcome as soon as possible for farther treatments. Methods: This retrospective cohort study included patients with ROSC after CPR who were admitted to our university hospital between January 2000 and May 2011 or an affiliated hospital between January 2006 and May 2011. Clinical parameters recorded on arrival included age (A), arterial blood pH (B), time from CPR to ROSC (C), pupil diameter (D), and initial rhythm (E). Glasgow outcome scale (GOS) was recorded at 6 months and the patients were divided according to favorable or unfavorable neurological outcomes based on GOS score. Multiple logistic regression analysis was performed to derive a formula to predict neurological outcomes based on basic clinical parameters. Results: The regression equation was derived using a teaching dataset consisting of 389 records: EP = 1/(1 + e-x), where EP is the estimated probability of having a favorable outcome, and x = (-0.034 × A) + (4.669 × B) - (0.105 × C) - (0.976 × D) + (2.603 × E) - 28.279. The sensitivity, specificity, and accuracy were 86%, 91% and 91%, respectively, for the validation dataset (n = 100). Conclusions: The 6 month neurological outcomes can be predicted in patients resuscitated from OHCA using clinical parameters that can be easily recorded at the site of CPR.

The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects

Sympathetic regulation of the cerebral circulation remains controversial. Although intravenous phenylephrine (PE) infusion reduces the near-infrared spectroscopy (NIRS)-determined measure of frontal lobe oxygenation (S(c) O(2) ) and increases middle cerebral artery mean blood velocity (MCA V(mean) ), suggesting α-adrenergic-mediated cerebral vasoconstriction, this remains unconfirmed by evaluation of arterial and venous cerebral blood flow. We determined S(c) O(2) , MCA V(mean) , and right internal carotid artery (ICA) and internal jugular venous (IJV) blood flow (duplex ultrasound) during infusion of PE in eight supine young healthy men [26 (3) years, 177 (7) cm and 74 (8) kg; mean (SD)]. Compared with saline, during infusion of PE, mean arterial pressure increased 26 ± 3% (mean ± SE) and MCA V(mean) by 4·8 ± 1·9% (P<0·05), while S(c) O(2) decreased by 13·7 ± 3·7% (P<0·05) with no significant changes in the arterial oxygen or carbon dioxide tensions. ICA blood flow did not change significantly in response to PE administration (351 ± 12 versus 373 ± 21 ml min(-1) ; P = 0·236), while IJV blood flow increased (443 ± 57 versus 507 ± 58 ml min(-1) ; P = 0·023). These findings confirm that PE induces a reduction in S(c) O(2) measured by NIRS and causes an increase in MCA V(mean) indicative of cerebral arterial vasoconstriction, although ICA was preserved and IJV increased. These results suggest that a decrease in S(c) O(2) during infusion of PE reflects an altered cerebral contribution of arterial versus venous blood to the NIRS signal, although we cannot rule out that an effect of PE on skin blood flow is important.

Bilateral Internal Jugular Venous Sampling for Parathyroid Hormone Determination in Patients with Nonlocalizing Primary Hyperparathyroidism

Focused parathyroidectomy (FP) is offered to 60% to 70% of patients presenting to our unit with primary hyperparathyroidism (PHPT). A recent report identified bilateral internal jugular venous sampling (BIJVS) as a useful tool for localization of parathyroid adenomas in patients with scan-negative PHPT. The purpose of this study was to evaluate the utility of this approach in a clinical setting. A prospective case-control trial was undertaken. Bilateral internal jugular venous blood samples were obtained. Patients were stratified into three groups: Group A consisted of patients with a negative sestamibi scan undergoing bilateral exploration; group B consisted of patients undergoing FP following a positive sestamibi scan; and group C patients were a control group undergoing total thyroidectomy. In group A, 17 of 30 patients (56%) had lateralization of the parathyroid hormone (PTH) levels, with 11 correctly lateralizing to the side of the adenoma, 5 lateralizing despite bilateral disease, and 1 lateralizing to the contralateral side. Of the remaining 13 patients in whom there was no lateralization, 3 had bilateral multigland disease, and 10 had a single parathyroid adenoma. In group B, 17 of 30 patients (56%) also had lateralization of PTH levels, with 15 lateralizing to the side of the adenoma and 2 to the contralateral side. Lateralization failed in the remaining 13 patients, although in all of these patients the calcium and PTH levels normalized postoperatively. The control group of patients without parathyroid disease (group C) demonstrated lateralization of PTH levels in 23 of 30 patients (76%). In our hands, BIJVS for PTH determination was not a useful adjunctive test facilitating FP. We continue to offer all patients with PHPT and a negative sestamibi scan a standard bilateral neck exploration.

Endurance training enhances BDNF release from the human brain

The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108 ng x 100 g(-1) x min(-1) (P < 0.05), with no significant change in the control subjects, but there was no training-induced increase in the release of BDNF during exercise. Additionally, eight mice completed a 5-wk treadmill running training protocol that increased the BDNF mRNA expression in the hippocampus (4.5 + or - 1.6 vs. 1.4 + or - 1.1 mRNA/ssDNA; P < 0.05), but not in the cerebral cortex (4.0 + or - 1.4 vs. 4.6 + or - 1.4 mRNA/ssDNA) compared with untrained mice. The increased BDNF expression in the hippocampus and the enhanced release of BDNF from the human brain following training suggest that endurance training promotes brain health.

Elevated Brain Serotonin Turnover in Patients With Depression

The biological basis for the development of major depressive disorder (MDD) remains incompletely understood. To quantify brain serotonin (5-hydroxytryptamine [5-HT]) turnover in patients with MDD. Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Studies were performed in 21 patients fulfilling the DSM-IV and International Statistical Classification of Diseases, 10th Revision diagnostic criteria for MDD and in 40 healthy volunteers. Treatment for patients consisted of SSRI administration for approximately 12 weeks. Brain serotonin turnover before and after SSRI therapy. Brain serotonin turnover was significantly elevated in unmedicated patients with MDD compared with healthy subjects (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 4.4 [4.3] vs 1.6 [2.4] nmol/L, respectively; P = .003). Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the l allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 [4.7] vs 2.7 [2.9] nmol/L, respectively; P = .04). Following SSRI therapy, brain serotonin turnover was substantially reduced (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.0 [4.0] nmol/L prior to treatment vs 2.0 [3.3] nmol/L following therapy; P = .008). Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD.

Human cerebrovascular and ventilatory CO2 reactivity to end‐tidal, arterial and internal jugular vein PCO2

This study examined cerebrovascular reactivity and ventilation during step changes in CO(2) in humans. We hypothesized that: (1) end-tidal P(CO(2)) (P(ET,CO(2))) would overestimate arterial P(CO(2)) (P(a,CO(2))) during step variations in P(ET,CO(2)) and thus underestimate cerebrovascular CO(2) reactivity; and (2) since P(CO(2)) from the internal jugular vein (P(jv,CO(2))) better represents brain tissue P(CO(2)), cerebrovascular CO(2) reactivity would be higher when expressed against P(jv,CO(2)) than with P(a,CO(2)), and would be related to the degree of ventilatory change during hypercapnia. Incremental hypercapnia was achieved through 4 min administrations of 4% and 8% CO(2). Incremental hypocapnia involved two 4 min steps of hyperventilation to change P(ET,CO(2)), in an equal and opposite direction, to that incurred during hypercapnia. Arterial and internal jugular venous blood was sampled simultaneously at baseline and during each CO(2) step. Cerebrovascular reactivity to CO(2) was expressed as the percentage change in blood flow velocity in the middle cerebral artery (MCAv) per mmHg change in P(a,CO(2)) and P(jv,CO(2)). During hypercapnia, but not hypocapnia, P(ET,CO(2)) overestimated P(a,CO(2)) by +2.4 +/- 3.4 mmHg and underestimated MCAv-CO(2) reactivity (P < 0.05). The hypercapnic and hypocapnic MCAv-CO(2) reactivity was higher ( approximately 97% and approximately 24%, respectively) when expressed with P(jv,CO(2)) than P(a,CO(2)) (P < 0.05). The hypercapnic MCAv-P(jv,CO(2)) reactivity was inversely related to the increase in ventilatory change (R(2) = 0.43; P < 0.05), indicating that a reduced reactivity results in less central CO(2) washout and greater ventilatory stimulus. Differences in the P(ET,CO(2)), P(a,CO(2)) and P(jv,CO(2))-MCAv relationships have implications for the true representation and physiological interpretation of cerebrovascular CO(2) reactivity.

The Utility of Intraoperative Bilateral Internal Jugular Venous Sampling With Rapid Parathyroid Hormone Testing

To determine the utility of routine perioperative bilateral internal jugular venous sampling of parathyroid hormone (BIJ PTH) for localization during parathyroid surgery. Venous sampling for PTH is a useful tool for parathyroid localization in patients undergoing reoperative surgery for hyperparathyroidism (HPT). With the development of intraoperative rapid PTH (ioPTH) testing, internal jugular PTH sampling with ioPTH testing to guide operative localization has been shown to be possible in select, difficult cases. However, the value of BIJ PTH for patients with HPT is unclear. Between May 2004 and February 2006, 216 consecutive patients underwent neck exploration for HPT by one surgeon. Of these, 168 patients had BIJ PTH. Internal jugular venous blood was drawn from both left and right sides and analyzed for PTH using a rapid PTH assay. BIJ PTH levels were defined as lateralizing if >5% differences were observed between the right and left internal jugular vein samples. Of the 168 patients, 120 (71.4%) had a single parathyroid adenoma, 15 (8.9%) had double adenoma, and 33 (19.6%) had hyperplasia. The cure rate after parathyroidectomy was 98.2%. There were no complications related to BIJ PTH sampling. Sensitivity and positive predictive value of BIJ PTH for primary hyperparathyroidism were 80% and 71%, respectively. BIJ PTH was diagnostic in 95 cases (62.9%) in primary HPT. BIJ PTH successfully localized an abnormal gland in 26 of 45 (57.8%) in patients with negative sestamibi scanning. BIJ PTH was especially helpful in 18 of 168 (10.7%) cases when intraoperative peripheral parathyroid hormone did not fall by 50% and BIJ PTH successfully localized the hyperfunctioning glands. In patients with HPT, BIJ PTH is safe and effective, providing additional localization information in the majority of cases. BIJ PTH is particularly useful in the setting of negative sestamibi scanning and in complex multigland disease cases.

Capillary-Oxygenation-Level-Dependent Near-Infrared Spectrometry in Frontal Lobe of Humans

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.