过敏性休克——一种没有抑制氧耗的分布性休克

背景：麻醉中发生过敏性休克的病理生理尚未完全阐明。它被认为是一种具有分布性的类似于感染性休克（无氧代谢，高组织氧压【PtiO2】）的一种休克形式。过敏性反应中组织氧压的情况及其结果至今尚未知晓。     

Anaphylactic Shock at the End of Hemodialysis

Allergic reactions to epoetin alfa, including anaphylaxis, have been described but desensitization in the setting of an IgE‐mediated reaction has not been reported. We present a case of a hemodialysis patient who developed symptoms of an IgE‐mediated allergic response to epoetin alfa that occurred after each administration. These reactions progressed to a single episode of anaphylaxis with generalized pruritus, urticaria, oropharyngeal edema, and hypotension that prompted its discontinuation. Intradermal skin testing confirmed an allergic response to this agent. The patient then underwent a desensitization procedure to epoetin alpha after which she was able to tolerate it without further problems.     

Anaphylactic Shock at the Beginning of Hemodialysis

In patients who receive hemodialysis, most hypersensitivity reactions to components of the dialysis circuit are due to ethylene oxide or complement activating bio‐incompatible membranes. We present a case of a 59 year‐old female, with a 4‐year history of uneventful hemodialysis using a cellulose based dialyzer membrane at her outpatient dialysis center, who developed repeated anaphylactic reactions associated with markers of an IgE mediated hypersensitivity reaction when a polysulfone based dialyzer membrane was used while she was hospitalized. Only when the patient's dialyzer was changed back to her usual cellulose based membrane, did these reactions cease. On the basis of her clinical course and laboratory findings, we concluded that the patient's symptoms were due to exposure to polysulfone. This case reminds us that “biocompatible” membranes are not free from dialyzer reactions, and can be especially severe if the mechanism is an IgE mediated anaphylactic hypersensitivity reaction.     

Anaphylactic Shock Caused by Nonruptured Hydatid Cyst of the Liver

Anaphylactic reaction is a known complication of cystic hydatid disease, a parasitic infestation caused by the larval/cyst stage of Echinococcus granulosus that usually happens after trauma or during interventions. Nontraumatic leakage of cyst contents into the blood circulation is an uncommon triggering factor for anaphylaxis, which is rarely reported in available literatures. We describe anaphylaxis in a 47-year-old lady who was admitted for evacuation of hydatid cyst of the liver. Unfortunately, she developed signs and symptoms of anaphylaxis in the ward while waiting for her operation. However, the condition was controlled immediately, and she was taken to the operating theater for surgery. As she had not sustained any trauma in the ward and operative exploration did not reveal any macroscopic rupture, we assumed that her problem must have been caused by nontraumatic spillage of cyst material into circulation. Although the condition is not common, one should bear in mind the possibility of such diagnosis in all patients with Eccinococcous infection who develop shock especially in areas where this infestation is endemic.     

Inhibition of De Novo Ceramide Synthesis Reverses Diet-Induced Insulin Resistance and Enhances Whole-Body Oxygen Consumption

OBJECTIVE

It has been proposed that skeletal muscle insulin resistance arises from the accumulation of intramyocellular lipid metabolites that impede insulin signaling, including diacylglycerol and ceramide. We determined the role of de novo ceramide synthesis in mediating muscle insulin resistance.

RESEARCH DESIGN AND METHODS

Mice were subjected to 12 weeks of diet-induced obesity (DIO), and then treated for 4 weeks with myriocin, an inhibitor of serine palmitoyl transferase-1 (SPT1), the rate-limiting enzyme of de novo ceramide synthesis.

RESULTS

After 12 weeks of DIO, C57BL/6 mice demonstrated a doubling in gastrocnemius ceramide content, which was completely reversed (141.5 ± 15.8 vs. 94.6 ± 10.2 nmol/g dry wt) via treatment with myriocin, whereas hepatic ceramide content was unaffected by DIO. Interestingly, myriocin treatment did not alter the DIO-associated increase in gastrocnemius diacyglycerol content, and the only correlation observed between lipid metabolite accumulation and glucose intolerance occurred with ceramide (R = 0.61). DIO mice treated with myriocin showed a complete reversal of glucose intolerance and insulin resistance which was associated with enhanced insulin-stimulated Akt and glycogen synthase kinase 3β phosphorylation. Furthermore, myriocin treatment also decreased intramyocellular ceramide content and prevented insulin resistance development in db/db mice. Finally, myriocin-treated DIO mice displayed enhanced oxygen consumption rates (3,041 ± 124 vs. 2,407 ± 124 ml/kg/h) versus their control counterparts.

CONCLUSIONS

Our results demonstrate that the intramyocellular accumulation of ceramide correlates strongly with the development of insulin resistance, and suggests that inhibition of SPT1 is a potentially promising target for the treatment of insulin resistance.Obesity and type 2 diabetes frequently occur hand in hand, and are thought of as diseases of Western society, due to lifestyles characterized by overnutrition and physical inactivity. This overnutrition manifests itself as hyperlipidemia, which is believed to be a major precipitating event in the development of skeletal muscle insulin resistance (1,2).Numerous studies in vivo and in vitro have provided strong evidence that lipid excess leads to an accumulation of intramyocellular lipid-derived metabolites, which coincide with an impaired insulin response (3,4). Previous studies have postulated that this accumulation of lipid-derived metabolites results from an impaired ability of the mitochondria to oxidize fatty acids (5–8). Thus, esterified fatty acids in the form of long-chain acyl-CoA are diverted away from carnitine palmitoyl transferase 1, the rate-limiting enzyme in the mitochondrial uptake and oxidation of fatty acids, toward triacylglycerol (TAG) and other lipid metabolites, such as ceramide and diacylglycerol (DAG). These metabolites are believed to activate classic/novel protein kinase C isoforms that phosphorylate and inactivate insulin receptor substrate proteins, preventing the insulin response at the level of Akt and GLUT4 translocation (3,4).Of the aforementioned lipid metabolites, ceramide is an attractive candidate to be a primary culprit involved in mediating the skeletal muscle insulin resistance seen with obesity and type 2 diabetes, as it is elevated by both inflammation and nutrient overload, and hence links two popular models of insulin-resistance development (9). Numerous studies in both culture and animal models demonstrate that increasing ceramide levels inhibit insulin signaling and cause insulin resistance (10–13). Moreover, Holland et al. showed that inhibiting de novo synthesis of ceramide by pharmacological inhibition of serine palmitoyl transferase one (SPT1) can prevent insulin resistance caused by corticosteroids, saturated fats, and genetic models of obesity (12). Pharmacological inhibition of SPT1 in human muscle cells has also been shown to prevent the inhibition of insulin-stimulated glycogen synthesis induced by palmitic acid (11). Finally, improvements in insulin sensitivity brought about by exercise training in obese patients are associated with significant reductions in intramyocellular ceramide levels, whereas TAG and DAG levels were either unchanged or showed only a trend to a reduction (14,15).Our objective in this investigation was to determine if inhibition of de novo ceramide synthesis could reverse the insulin resistance induced by chronic high-fat feeding of mice, and to gain a further understanding of how ceramides affect insulin sensitivity in muscle.     

Anaphylactic shock: a form of distributive shock without inhibition of oxygen consumption

BACKGROUND: The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known. METHODS: Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes. RESULTS: In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x 100 g(-1) x min(-1); P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P < 0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05). CONCLUSIONS: This profile suggests decreased skeletal muscle blood flow and oxygen delivery. Persistent energy consumption results in decreased Ptio2 and substrate depletion through anaerobic glycolysis leading to complete failure of cellular energy production. This could explain rapid organ dysfunction and resuscitation difficulties.     

Discontinuation of Living Donor Liver Transplantation due to Donor's Intraoperative Latex-Induced Anaphylactic Shock

We report on a 33-year-old female liver donor candidate who developed intraoperative latex-induced anaphylactic shock during surgery for living donor transplantation. She was the mother of the organ recipient, who was a 9-year-old boy with biliary atresia. We planned extended lateral segmentectomy for her. Although we dissected the ligament around the left lobe, the systolic blood pressure suddenly dropped and her body became flushed and warm. We administered transfusion and an ephedrine injection to recover the blood pressure. Because she recovered after the treatment, we restarted the procedure. However, she went into shock again within a few minutes. We decided to discontinue the operation. Postoperative blood tests revealed an increase in IgE-RAST and basophil activation, suggesting that the anaphylactic shock was induced by latex. Because latex allergy has become a public health problem, this allergy should be kept in mind as a potential donor operation risk.     

过敏性休克--一种没有抑制氧耗的分布性休克

背景:麻醉中发生过敏性休克的病理生理尚未完全阐明。它被认为是一种具有分布性的类似于感染性休克(无氧代谢,高组织氧压【PtiO2】)的一种休克形式。过敏性反应中组织氧压的情况及其结果至今尚未知晓。方法:卵白蛋白致敏的过敏性休克小鼠(n=11)组与尼卡地平诱导的低血压小鼠(n=12)组,分别比较它们的全身血流动力学数据,组织氧压,交感神经系统的活化情况,骨骼肌血流量,还有联合使用微型透析和极谱描记的clark型氧探针测得间质的乳酸与丙酮酸浓度。结果:两组的实验数据随时间的变化趋势与动脉低压变化相类似。卵白蛋白组显示出骨骼肌血流量的…     

Nitroprusside-Hypotension: Cerebral Blood Flow and Cerebral Oxygen Consumption in Neurosurgical Patients

The effects of nitroprusside-induced hypotension on cerebral blood flow and cerebral oxygen consumption were investigated in nine patients scheduled for cerebral arterial aneurysm surgery. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl; muscle relaxation was achieved with pancuronium; Paco₂ was maintained at 4.79-5.32 kPa. Mean arterial pressure was reduced to 50 mm Hg by nitroprusside infusion after opening of the dura. Measurements were recorded and blood samples were taken 15 min before induction of hypotension, during stable hypotension and 15 min after termination of nitroprusside infusion. Measurements included: cerebral blood flow, using the argon-washin technique, cardiac output (thermodilution), mean arterial pressure and heart rate. Cerebral blood flow averaged 56 ± 6 ml/min. 100 g before hypotension. Nitroprusside produced hypotension but did not significantly alter cerebral blood flow (61 ± 7 ml/min · 100 g). Cerebral blood flow remained virtually at preinfusion values upon cessation of infusion (53 ± 6 ml/min · 100 g). Cerebral oxygen uptake averaged 3 ± 0.2 ml/min · 100 g before hypotension and did not change significantly during hypotension (3.3 ± 0.3 ml/min · 100 g) and after termination of hypotension (2.7 ± 0.3 ml/min · 100 g). In two patients nitroprusside produced a 17 and 20% increase, respectively, in cerebral blood flow with no change in cerebral oxygen consumption, together with a marked increase in cardiac output and heart rate.     

Effect of Caspase Inhibition on Thymic Apoptosis in Hemorrhagic Shock

In hemorrhagic shock (HS) an increased thymic apoptosis (TA) was described. The aim of this study was to evaluate the effect of administration of the caspase inhibitor N-benzyloxy-carbonil-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) during the resuscitation phase on TA, organ dysfunctions, and tumor necrosis factor (TNF)-α release in HS. Forty rats were randomly assigned to four groups: no HS/resuscitation (sham); HS/resuscitation with shed blood and normal saline (control); HS/resuscitation with shed blood and phosphate-buffered solution (PBS) (vehicle); and HS/resuscitation with shed blood and Z-VAD-FMK (inhibitor). Rats were subjected to HS by blood removal to a MAP of 35–40 mmHg. After a 1-h shock period, the animals were resuscitated according to the protocol. At 1 and 3 h after resuscitation, transaminases, creatinine, urea, lipase, TNF-α, and TA were evaluated. Our study showed that a nonlethal HS is early able to induce organ dysfunctions and increased TA. Administration of Z-VAD-FMK did not significantly decrease organ dysfunctions, while it induced a significant TNF-α release. TA was significantly reduced by Z-VAD-FMK after 1 h, but not after 3 h. Our results suggest that postinjury caspase inhibition does not attenuate organ dysfunctions, and also does not permanently reduce TA induced by HS and resuscitation in rats.     

Continuous Real-time Viability Assessment of Kidneys Based on Oxygen Consumption

Background

Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation.

Methods

Five porcine kidneys were procured using a donation after cardiac death (DCD) model. The renal artery and renal vein were cannulated and the kidney connected to a custom-made hypothermic machine perfusion (HMP) system equipped with an inline oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8°C, and the perfusion parameters and partial oxygen pressures (pO₂) were measured to calculate WOOCR.

Results

Without an inline oxygenator, the pO₂ of the perfusion solution at the arterial inlet and venous outlet diminished to near 0 within minutes. However, once adequate oxygenation was provided, a significant pO₂ difference was observed and used to calculate the WOOCR. The WOOCR was consistently measured from presumably healthy kidneys, and results suggest that it can be used to differentiate between healthy and purposely damaged organs.

Conclusions

Custom-made HMP systems equipped with an oxygenator and inline oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a promising approach for the real-time quality assessment of kidneys and other organs during preservation before transplantation.     

Cardiopulmonary Exercise Testing with Elastic Resistance: A New Reproducible Proposal for Determination of Ventilatory Thresholds and Maximum Oxygen Consumption

To propose a new Cardiopulmonary Exercise Test with Elastic Resistance (CPxEL) and compare the physiological responses to conventional cardiopulmonary exercise test (CPx) performed on a treadmill. In addition, we tested the reproducibility of the CPxEL. Twenty-four physically active participants completed the CPx (first session) and CPxEL twice (second and third sessions) interspersed by seven days. A treadmill protocol with increments of 1km·h^-1 every minute until exhaustion was used in CPx. The CPxEL consisted of performing alternating steps back-and-forth against an elastic resistance attached to a belt and an incremental protocol with 1 stage (S) per minute following a cadence of 200 bpm controlled by a metronome in an 8-stage rubber mat. First analysis: first ventilatory threshold (VT1) occurred at 69.7% and 75.3% of maximal heart rate (HR_max) and 53.5% and 65.7% of maximal oxygen consumption (V̇O_2max). Second VT (VT2) occurred at 93.3% and 96.8% of the HR_max and 87.0% and 96.9% of V̇O_2max for CPx and CPxEL, respectively. At exhaustion, V̇O_2max, perceived exertion (BORG-CR10 and OMNI-RES EB), and test duration presented lower values for CPxEL (P < 0.05). Second analysis: VT1 occurred at warm-up (S0) (P = 0.731), VT2 occurred at S5 (P = 0.912), and the exhaustion occurred at S6 and S7 (P = 0.271) for CPxEL and retest, respectively. The intraclass correlation coefficient (ICC) for V̇O_2max was 0.921 and for HR_max was 0.930. The CPxEL has good test-retest reproducibility and represents a possible and interesting add-on to determine maximal oxygen consumption, maximal heart rate, and second ventilatory threshold without using traditional ergometers. Key points

• The CPxEL represents a possible and interesting add-on to the CPx, not requiring treadmills or ergometers.
• The CPxEL has good test-retest reproducibility and represents a possible and interesting add-on to determine maximal oxygen consumption and heart rate.
• Using back-and-forth movements alternating strides with elastic resistance in an 8-stage rubber mat can be applied to measure maximal (V̇O₂max) and submaximal capacity (VT2).

Key words: Cardiopulmonary exercise test, ventilatory thresholds, exercise testing, accessibility