Burst Activation of the Cerebral Cortex by Flash Stimuli during Isoflurane Anesthesia in Rats

Background: The degree of suppression of sensory functions during general anesthesia is controversial. Here, the authors investigated whether discrete flash stimuli induced cortical field potential responses at an isoflurane concentration producing burst suppression and compared the spatiotemporal properties and frequency spectra of flash-induced burst responses with those occurring spontaneously.

Methods: Rats were equipped with multiple epidural and intracortical electrodes to record cortical field potentials in the right hemisphere at several locations along the anterior-posterior axis. At isoflurane concentrations of 1.1, 1.4, and 1.8%, discrete light flashes were delivered to the left eye while cortical field potentials were continuously recorded.

Results: Isoflurane at 1.4-1.8% produced burst suppression. Each flash produced a visual evoked potential in the primary visual cortex followed by secondary bursting activity in more anterior regions. The average latency and duration of these bursts were 220 and 810 ms, respectively. The spontaneous and flash-induced bursts were similar in frequency, duration, and spatial distribution. They had maximum power in the frontal (primary motor) cortex with a dominant frequency of 10 Hz.     

Electroencephalographic Bicoherence Is Sensitive to Noxious Stimuli during Isoflurane or Sevoflurane Anesthesia

Background: The authors previously reported changes in electroencephalographic bicoherence during isoflurane anesthesia combined with epidural anesthesia. Here, they examined the influence of noxious stimuli on electroencephalographic bicoherence as well as on the Bispectral Index (BIS) and the 95% spectral edge frequency (SEF95).

Methods: The authors enrolled 48 elective abdominal surgery patients (aged 22-77 years; American Society of Anesthesiologists physical status I or II). Raw electroencephalographic signals as well as BIS and SEF95 were recorded on a computer using a BIS(R) monitor (A-1050) and Bispectrum Analyzer (BSA) for BIS (the authors' original software). Using BSA for BIS, the authors evaluated the two peak heights of electroencephalographic bicoherence. Anesthesia was induced with 3 mg/kg thiopental and was maintained with, in air-oxygen, 1.0% isoflurane or 1.5% sevoflurane. After confirming the steady state, the authors recorded baseline values. In experiment 1, they administered 3 [mu]g/kg fentanyl 5 min after incision and investigated the changes in electroencephalographic derivatives at 5 and 10 min after incision. In experiment 2, they administered a similar dose of fentanyl 5 min before incision and investigated the changes in electroencephalographic derivatives immediately before and 5 min after incision.

Results: In experiment 1, after incision, both peak heights of electroencephalographic bicoherence significantly decreased but returned to control values after fentanyl administration. By contrast, after incision, BIS and SEF95 showed individual variability. In experiment 2, although fentanyl itself did not affect all electroencephalographic derivatives before incision, the variables remained unchanged after incision.     

Nitrous Oxide-induced Enhancement of gamma-Aminobutyric Acid sub A-mediated Chloride Currents in Acutely Dissociated Hippocampal Neurons

Background: Because the synaptic inhibition in the human brain is largely mediated by gamma-aminobutyric acid (GABA), the GABA receptor is of primary interest for the study of the working mechanism of general anesthetics. This article examines the interaction between this type of ion channel and nitrous oxide (N2 O).

Methods: Patch clamp recording techniques were applied to investigate the effects of N2 O on GABAA receptor channels in a whole-cell configuration at room temperature. Acutely dissociated rat hippocampal cells from the CA1 region were used. Rapid application of the agonist muscimol and anesthetics (N2 O, pentobarbital, and ethanol) was accomplished using a Y tube application system. Peak chloride (Cl sup -) currents were measured.

Results: Short-term application of muscimol (5-30 micro Meter) with dissolved N2 O (80%, [nearly =] 22.5 mM) increased the Cl sup - current ([nearly =] 140%) compared with muscimol alone. This effect is comparable with results the authors obtained with ethanol (800 mM) and pentobarbital (100 micro Meter). Prolonged exposure (9 min) to N2 O further increased Cl sup - currents by an additional 50%. Concentrations of N2 O lower than 12 mM did not show an enhancement of this current, whereas application of N2 O alone did not result in any Cl sup - conductance.     

Three-dimensional In Vivo Quantification of Knee Kinematics in Cerebral Palsy

Cerebral palsy is the most common disabling condition in childhood, involving a diverse group of movement and posture disorders of varying etiologies. Yet, much is unknown about how cerebral palsy affects individual joints because currently applied techniques cannot quantify the three-dimensional kinematic parameters at the joint level. We quantified the effects of cerebral palsy at the knee using fast phase contrast MRI, with the ultimate intent of improving the assessment of joint impairments associated with cerebral palsy, improving clinical outcomes, and reducing the impact of cerebral palsy on function. We addressed three questions: (1) Can patients with cerebral palsy perform the required repetitive extension task? (2) Which of the 12 degrees of freedom defining complete knee kinematics are abnormal in individual patients with cerebral palsy and is the patellar tendon moment arm abnormal in these patients? (3) Are the individual kinematic differences consistent with clinical observations? All patients were able to perform the required task. We found kinematic differences for each patient with cerebral palsy consistent with clinical findings, in comparison to an able-bodied population. Fast phase contrast MRI may allow differentiation of patellofemoral and tibiofemoral function in various functional subtypes of cerebral palsy, providing insights into its management.     

Effect of Systemic Morphine on the Responses of Convergent Neurons to Noxious Heat Stimuli Applied over Graded Surface Areas

Background: Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord.

Methods: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2).

Results: The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11 +/- 4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159 +/- 36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42 +/- 24% of control values; P < 0.05) than was observed with the smaller stimulus.     

In Vivo Evaluation of Platelet Activation by Different Cellulosic Membranes

Abstract: This study was undertaken to evaluate platelet activation in vivo induced by different cellulosic membranes by measuring the expression of P-selectin on the platelet surface during hemodialysis in 9 uremic patients. Hollow fiber dialyzers of similar surface with different cellulosic membranes (Cuprophan, cellulose acetate, cellulose triacetate, and Hemophan) were evaluated and compared to a synthetic membrane (polysulfone). Blood samples were obtained before hemodialysis and from the efferent and afferent limbs 5 min after the beginning of dialysis. P-select in exposure was evaluated by flow cytometry (FACScan) using a monoclonal antibody (RUU 2.17). The percentage of platelets expressing P-select in before hemodialysis and the percentage from the arterial line during hemodialysis were similar. All membranes evaluated induced platelet activation (estimated as the increase in percentage of platelets expressing P-selectin in samples obtained from the venous line with respect to the arterial line). Cuprophan induced more platelet activation than any other membrane (p < 0.05). The activation induced by cellulose acetate and cellulose triacetate membranes was also higher than that observed with Hemophan (p < 0.05). Hemophan-induced platelet activation was similar to that of polysulfone. These results indicate that all cellulosic membranes induce platelet activation during hemodialysis although there are quantitative differences among them. While Cuprophan induced the highest degree of platelet activation, Hemophan was the only cellulosic membrane that showed a degree of platelet activation similar to the biocompatible membrane polysulfone.     

Modification by Baroreceptor Feedback of Circulatory Responses to Noxious Stimuli During Anaesthesia in Cats

In eight cats anaesthetized with chloralose, the carotid sinus on one side was either exposed to systemic arterial pressure or perfused with a pump in order to control sinus pressure. Baroreceptor influences from the contralateral carotid sinus and from the aortic arch were interrupted by denervation. Arrangements were made for intermittent electric stimulation of pain fibres in somatic and visceral nerves with stimulation parameters chosen to elicit reproducible increases in arterial blood pressure and in skeletal muscle vascular resistance. The elicited increases in arterial pressure and muscle vascular resistance were both about 40% smaller when the carotid sinus was exposed to systemic arterial pressure in comparison with the experimental condition of a constant carotid sinus pressure. I.v. metoprolol (0.1-0.3 mg kg-1) reduced base-line arterial pressure, but did not attenuate the arterial blood pressure increase in response to pain stimulation. The baroreceptor modulation of the haemodynamic response to the pain stimulation was not affected by metoprolol.     

In Vivo Fluorescence Imaging of Gastrointestinal Stromal Tumors Using Fluorophore-Conjugated Anti-KIT Antibody

Background

Gastrointestinal stromal tumors (GISTs) are frequently characterized by KIT overexpression. Tumor-free margins and complete cytoreduction of disease are mainstays of treatment. We hypothesized that fluorescently labeled anti-KIT antibodies can label GIST in vivo.

Methods

KIT K641E^+/− transgenic mice that spontaneously develop cecal GISTs were used in this study, with C57BL/6 mice serving as controls. Alexa 488 fluorophore-conjugated anti-KIT antibodies were delivered via the tail vein 24 h prior to fluorescence imaging. Following fluorescence laparoscopy, mice were sacrificed. The gastrointestinal tracts were grossly examined for tumors followed by fluorescence imaging. Tumors were harvested for histologic confirmation.

Results

KIT K641E^+/− mice and C57BL/6 control mice received anti-KIT antibody or isotope control antibody. Fluorescence laparoscopy had a high tumor signal-to-background noise ratio. Upon blinded review of intravital fluorescence and bright light images, there were 2 false-positive and 0 false-negative results. The accuracy was 92 %. The sensitivity, specificity, positive and negative predictive values were 100, 87, 85, and 100 %, respectively, for the combined modalities.

Conclusions

In this study, we present a method for in vivo fluorescence labeling of GIST in a murine model. Several translatable applications include: laparoscopic staging; visualization of peritoneal metastases; assessment of margin status; endoscopic differentiation of GISTs from other benign submucosal tumors; and longitudinal surveillance of disease response. This novel approach has clear clinical applications that warrant further research and development.

     

Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals

Purpose of Review

Connecting organ-scale loads to cellular signals in their local in vivo environment is a current challenge in the field of bone (re)modelling. Understanding this critical missing link would greatly improve our ability to anticipate mechanotransduction during different modes of stimuli and the resultant cellular responses. This review characterises computational approaches that could enable coupling links across the multiple scales of bone.

Recent Findings

Current approaches using strain and fluid shear stress concepts have begun to link organ-scale loads to cellular signals; however, these approaches fail to capture localised micro-structural heterogeneities. Furthermore, models that incorporate downstream communication from osteocytes to osteoclasts, bone-lining cells and osteoblasts, will help improve the understanding of (re)modelling activities. Incorporating this potentially key information in the local in vivo environment will aid in developing multiscale models of mechanotransduction that can predict or help describe resultant biological events related to bone (re)modelling.

Summary

Progress towards multiscale determination of the cell mechanical environment from organ-scale loads remains elusive. Construction of organ-, tissue- and cell-scale computational models that include localised environmental variation, strain amplification and intercellular communication mechanisms will ultimately help couple the hierarchal levels of bone.

     

Activation of AMP-Activated Protein Kinase Inhibits Oxidized LDL-Triggered Endoplasmic Reticulum Stress In Vivo

OBJECTIVE

The oxidation of LDLs is considered a key step in the development of atherosclerosis. How LDL oxidation contributes to atherosclerosis remains poorly defined. Here we report that oxidized and glycated LDL (HOG-LDL) causes aberrant endoplasmic reticulum (ER) stress and that the AMP-activated protein kinase (AMPK) suppressed HOG-LDL–triggered ER stress in vivo.

RESEARCH DESIGN AND METHODS

ER stress markers, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA) activity and oxidation, and AMPK activity were monitored in cultured bovine aortic endothelial cells (BAECs) exposed to HOG-LDL or in isolated aortae from mice fed an atherogenic diet.

RESULTS

Exposure of BAECs to clinically relevant concentrations of HOG-LDL induced prolonged ER stress and reduced SERCA activity but increased SERCA oxidation. Chronic administration of Tempol (a potent antioxidant) attenuated both SERCA oxidation and aberrant ER stress in mice fed a high-fat diet in vivo. Likewise, AMPK activation by pharmacological (5′-aminoimidazole-4-carboxymide-1-β-d-ribofuranoside, metformin, and statin) or genetic means (adenoviral overexpression of constitutively active AMPK mutants) significantly mitigated ER stress and SERCA oxidation and improved the endothelium-dependent relaxation in isolated mouse aortae. Finally, Tempol administration markedly attenuated impaired endothelium-dependent vasorelaxation, SERCA oxidation, ER stress, and atherosclerosis in ApoE^−/− and ApoE^−/−/AMPKα2^−/− fed a high-fat diet.

CONCLUSION

We conclude that HOG-LDL, via enhanced SERCA oxidation, causes aberrant ER stress, endothelial dysfunction, and atherosclerosis in vivo, all of which are inhibited by AMPK activation.LDL oxidation and glycation are known to promote atherosclerosis through several mechanisms that include promoting vascular proinflammatory responses, intracellular oxidative stress, and apoptosis associated with endothelial dysfunction (1,2). In addition, LDL oxidation is greatly enhanced by LDL glycation (3,4). For example, glycation of LDL slows the clearance of these particles from the circulation (5), increases their susceptibility to oxidative damage (6), enhances entrapment of extravasated particles in the vascular subintimal space, and increases chemotactic activity of monocytes (7). The presence of both glycated LDL and glycoxidized LDL in human atherosclerotic plaques has been confirmed by immunochemical methods both in vivo and in vitro (8–10). Increasing evidence suggests that glycation and oxidation of LDL induces apoptosis in arterial wall cells (11,12), and glycoxidized LDL triggers apoptosis in vascular smooth muscle cells (13,14). Overall, glycation of LDL promotes the formation of oxidized LDL, and this phenomenon contributes to accelerated atherosclerosis, an important pathologic corollary of diabetes.Endoplasmic reticulum (ER) stress has been linked to a wide range of human pathologies including diabetes (15–17), obesity (16,17), atherosclerosis (18), cancer, neurodegenerative disorders, and inflammatory conditions. ER stress may be triggered by high glucose, oxidative stress, Ca²⁺ overload, ischemia, and hypoxia. In addition, it causes the accumulation of unfolded and misfolded proteins, leading to an “unfolded protein response” (19). The normal ER is the principal site of protein synthesis, folding, and maturation. In unfolded protein response, unfolded or misfolded proteins are sent to the cytoplasm by a “retro-translocation mechanism” to be degraded by the ubiquitin proteasome system (20).AMP-activated protein kinase (AMPK), a sensor of cellular energy status, plays a critical role in controlling the cell''s energy balance and metabolism (21), and activation of AMPK is an important defensive response to stress (22). AMPK activation is neuroprotective (23), and also mediates at least some cardiovascular protective effects of drugs such as hydroxymethylglutaryl-CoA reductase inhibitors (e.g., the statins such as pravastatin and atorvastatin) and metformin (a biguanide that activates AMPK) (24,25). Activation of AMPK protects cardiomyocytes against hypoxic injury through attenuation of ER stress (26). However, whether AMPK alters oxidized LDL-induced ER stress in endothelial cells has not been investigated to date. In this study, we report that oxidized, glycated-LDL (HOG-LDL) via the oxidation and inhibition of sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA), triggers ER stress in endothelial cells in vivo. In addition, we have uncovered evidence suggesting that AMPK activation attenuates ER stress by inhibiting SERCA oxidation caused by HOG-LDL.     

In Vivo Activation of AMP-Activated Protein Kinase Attenuates Diabetes-Enhanced Degradation of GTP Cyclohydrolase I

OBJECTIVE

The activation of AMP-activated protein kinase (AMPK) has been reported to improve endothelial function. However, the targets of AMPK in endothelial cells remain poorly defined. The aim of this study was to test whether AMPK suppresses the degradation of GTP-cyclohydrolase (GTPCH I), a key event in vascular endothelial dysfunction in diabetes.

RESEARCH DESIGN AND METHODS

Both human umbilical vein endothelial cells and aortas isolated from streptozotocin-injected diabetic mice were assayed for phospho-AMPK (Thr172), GTPCH I, tetrahydrobiopterin (BH4), and endothelial functions.

RESULTS

Oral administration of metformin (300 mg · kg⁻¹ · day⁻¹, 4 weeks) in streptozotocin-injected mice significantly blunted the diabetes-induced reduction of AMPK phosphorylation at Thr172. Metformin treatment also normalized acetylcholine-induced endothelial relaxation and increased the levels of GTPCH I and BH4. The administration of AICAR, an AMPK activator, or adenoviral overexpression of a constitutively active mutant of AMPK abolished the high-glucose–induced (30 mmol/l) reduction of GTPCH I, biopeterins, and BH4 but had no effect on GTPCH I mRNA. Furthermore, AICAR or overexpression of AMPK inhibited the high-glucose–enhanced 26S proteasome activity. Consistently, inhibition of the proteasome by MG132 abolished high-glucose–induced reduction of GTPCH I in human umbilical vein endothelial cells. Further, aortas isolated from AMPKα2^−/− mice, which exhibited elevated 26S proteasome activity, had reduced levels of GTPCH I and BH4. Finally, either administration of MG132 or supplementation of l-sepiapterin normalized the impaired endothelium-dependent relaxation in aortas isolated from AMPKα2^−/− mice.

CONCLUSIONS

We conclude that AMPK activation normalizes vascular endothelial function by suppressing 26S proteasome-mediated GTPCH I degradation in diabetes.The most important factor for the maintenance of vascular homeostasis is nitric oxide (NO), derived from l-arginine in the catalysis of endothelial nitric oxide synthase (eNOS). Many studies have indicated that diabetes alters the metabolism and function of endothelium in ways that could lead to vascular injury (1). In diabetes, the function of eNOS is altered such that the enzyme produces superoxide anion (O₂^–·) rather than NO (2). This phenomenon is referred to as eNOS uncoupling and has been reported to play a causal role in diabetes-enhanced endothelial dysfunction (3,4). Several studies (5) have suggested that deficiency of tetrahydrobiopterin (BH4), an essential cofactor for eNOS, transforms eNOS into an oxidant-producing enzyme, leading to the production of O₂⁻· and/or peroxynitrite (ONOO^–·).Intracellular BH4 levels are dictated by a balance of de novo synthesis, BH4 oxidation, and recycling of BH2 to BH4 (6). De novo synthesis of BH4 is controlled by GTP cyclohydrolase I (GTPCH I), a homodecameric protein consisting of 25 kDa subunits in mammalian cells (7). As the first enzyme in the biosynthetic pathway of BH4, GTPCH I is constitutively expressed in endothelial cells and critical for the maintenance of BH4 levels and NO synthesis. Indeed, acute inhibition of GTPCH I uncouples eNOS, induces endothelial dysfunction, and elevates blood pressure in vivo (8). Further, our recent study (9) suggests that hyperglycemia uncouples eNOS by reducing the levels of GTPCH I and BH4.Proteasomes provide a major pathway of intracellular protein degradation in mammalian cells (10–12). Although proteasomes can degrade proteins by ubiquitin-independent processes, they are mostly involved in the ATP- and ubiquitin-dependent pathway of protein degradation (13). The 26S proteasome complex consists of both the 20S catalytic core, where the proteins are degraded, and 19S complex, a regulatory subunit composed of at least 19 different subunits that form a lid- and a base-like structure; the lid provides the binding sites for poly-ubiquitinated substrates and a deubiquitinating activity involved in the recycling of ubiquitin moieties upon substrate degradation; the base includes six ATPases that interact with the 20S proteolytic core. The ATPases have chaperone functions and are required for the unfolding of substrates and their translocation into the 20S proteolytic chamber (14,15). Therefore, intracellular protein degradation by the proteasome is a highly energy-demanding process and, thus, it is expected that under conditions of energy depletion this process should be tightly regulated. The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes has been addressed (16,17).The AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of α, β, and γ subunits. The α (α1 and α2) subunit imparts catalytic activity, whereas the other subunits maintain the stability of the heterotrimer complex (18). Activation of AMPK requires the phosphorylation of AMPK at Thr172 in the activative loop of the α subunit (19), and is mediated by at least two kinases, Peutz-Jeghers syndrome kinase LKB1 (20) and Ca²⁺/calmodulin-dependent protein kinase kinase (21). AMPK is considered an “energy gauge,” which becomes activated when intracellular AMP increases and/or ATP decreases. Recently, Rosa Viana et al. (22) reported that AMPK suppresses proteasome-dependent protein degradation in vitro. As our earlier study (9) demonstrated that proteasome-dependent GTPCH I degradation is key for diabetes-induced endothelial dysfunction, we reasoned that AMPK activation might alleviate diabetic endothelial dysfunction by suppressing proteasome-dependent GTPCH I degradation. Here, we report that pharmacological or genetic activation of AMPK reversed endothelial dysfunction by suppressing GTPCH I degradation.     

Joint Changes after Overuse and Peak Overloading of Rabbit Knees In Vivo

The effect of overuse and overuse combined with axial peak overloading on the knee joints of living rabbits has been investigated. A specially constructed apparatus was used for this purpose. Physical and biochemical changes are reported and include:

1. Early and progressive damage to the articular cartilage surface shown by the scanning electron microscope.

2. The presence of an increased amount of prostaglandin E in the synovial fluid.

3. A reduction of cyclic 3′-5′ adenosine monophosphate in the subchondral bone.

4. Late changes which were consistent with osteoarthritis.

These changes were found only in the joints subjected to simultaneous overuse and peak overloading.

The results suggest that:

1. Cartilage damage and chemical changes in the subchondral bone are simultaneous and are both responsible for eventual degenerative changes.

2. Frictional overuse alone does not seem to be responsible for the production of osteoarthritis.     

Joint Changes after Overuse and Peak Overloading of Rabbit Knees In Vivo

The effect of overuse and overuse combined with axial peak overloading on the knee joints of living rabbits has been investigated. A specially constructed apparatus was used for this purpose. Physical and biochemical changes are reported and include:

1. Early and progressive damage to the articular cartilage surface shown by the scanning electron microscope.

2. The presence of an increased amount of prostaglandin E in the synovial fluid.

3. A reduction of cyclic 3'-5' adenosine monophosphate in the subchondral bone.

4. Late changes which were consistent with osteoarthritis.

These changes were found only in the joints subjected to simultaneous overuse and peak overloading.

The results suggest that:

1. Cartilage damage and chemical changes in the subchondral bone are simultaneous and are both responsible for eventual degenerative changes.

2. Frictional overuse alone does not seem to be responsible for the production of osteoarthritis.     

In Vivo Imaging of Human Pancreatic Microcirculation and Pancreatic Tissue Injury in Clinical Pancreas Transplantation

Pancreatitis remains to be a major complication following clinical pancreas transplantation. We performed orthogonal polarized spectral (OPS) imaging for direct in vivo visualization and quantification of human pancreatic microcirculation in six healthy donors for living donor liver transplantation and 13 patients undergoing simultaneous pancreas-kidney transplantation. We further determined the impact of microvascular dysfunction during early reperfusion on pancreatic graft injury. Exocrine and endocrine pancreatic impairment was determined by analysis of serum lipase, amylase and C-peptide levels. Compared to normal pancreas in liver donors (homogeneous acinar perfusion) functional capillary density (FCD) and capillary red blood flow velocity of reperfused grafts were significantly decreased. Elevated CRP concentrations on day 2 post-transplant and serum lipase and amylase levels determined on days 4-5 significantly correlated with microvascular dysfunction during the first 30 min of graft reperfusion. Post-transplant serum C-peptide also correlated significantly with pancreatic capillary perfusion. OPS imaging allows to intra-operatively assess physiologic pancreatic microcirculation and to determine microcirculatory impairment during early graft reperfusion. This impairment correlated with the manifestation of post-transplant dysfunction of both exocrine and endocrine pancreatic tissue. OPS imaging may be used clinically to determine the efficacy of interventions, aiming at attenuating microcirculatory impairment during the acute post-transplant reperfusion phase.     

In Vivo Optical Imaging of Pleural Space Drainage to Lymph Nodes of Prognostic Significance

Background: Understanding the spatial and temporal drainage patterns of the pleural space could have profound impact on the treatment of lung cancer and mesothelioma. The purpose of this study was to identify the in vivo pattern of drainage from the pleural space to prognostic lymph node stations.Methods: Fifty-six rats underwent pleural space injection of a novel lymph tracer composed of recombinant human serum albumin (HSA) covalently conjugated to the near-infrared (NIR) fluorophore IRDye78 via an amide bond (HSA-78). Nodal uptake was imaged at 10, 20, 30, and 60 minutes and 4, 12, and 24 hours after injection with a custom system that simultaneously acquires color video, NIR fluorescence of HSA-78, and a merged picture of the two. Six pigs underwent the same procedure with imaging at 30 minutes, 1 hour, and 24 hours.Results: In both the rat model and the pig model, HSA-78 drained from the pleural space to superior mediastinal lymph nodes first, followed by other intrathoracic and then extrathoracic lymph nodes over the course of 24 hours.Conclusion: NIR fluorescence imaging in two species shows that the superior mediastinal lymph nodes are the first to drain the pleural space. Over the course of 24 hours, the pleural space also communicates with other intrathoracic and then extrathoracic lymph nodes. This study also demonstrates an intraoperative method for identifying nodes communicating with the pleural space, with potential utility in the staging and/or resection of lung cancer and mesothelioma.     

Haemodynamic Changes during Sodium Nitroprusside Induced Hypotension and Halothane/Nitrous Oxide Anaesthesia

The haemodynamic effects of nitroprusside (SNP) were studied in six patients undergoing surgery for intracranial aneurysm under controlled hypotension in endotracheal anaesthesia with halothane-nitrous oxide during hypocapnia. Mean arterial pressure was reduced with SNP from mean 12.25 kPa to mean 8.29 kPa (32%). There were concomitant statistically significant decreases in systemic vascular resistance (-21%), cardiac index (-17%), stroke index (-23%), pulmonary arterial mean pressure (-27%) and pulmonary capillary wedge pressure (-27%). Heart rate, central venous pressure and pulmonary vascular resistance did not change significantly. After the infusion of SNP was discontinued all parameters, except cardiac index and heart rate, returned to values not significantly different from the control values. The hypotension induced by SNP resulted from reductions in cardiac index and systemic vascular resistance. The reduction in cardiac index did not reach a critical level in any of the patients.     

颈丛神经阻滞期脑氧饱和度的变化

目的与方法：随机选择３０例ＡＳＡⅠ级的甲状腺腺瘤病人，在双侧颈丛神经阻滞下行甲状腺腺瘤摘除术，术中测定ｒＳＯ２、ＳｐＯ２、ＢＰ、ＨＲ和ＥＣＧ。结果：所有病人术中ｒＳＯ２值均在正常范围内，ＳｐＯ２、ＢＰ、ＨＲ没有明显的改变，且ｒＳＯ２和ＳｐＯ２、ｒＳＯ２与ＢＰ，ｒＳＯ２与ＨＲ没有相关性。结论：颈丛神经阻滞对病大人脑的氧供需平衡影响极小，是一种安全简单有效的麻醉方法。