Low-dose Lidocaine Suppresses Experimentally Induced Hyperalgesia in Humans

Background: The antinociceptive effects of systemically administered local anesthetics have been shown in various conditions, such as neuralgia, polyneuropathy, fibromyalgia, and postoperative pain. The objective of the study was to identify the peripheral mechanisms of action of low-dose local anesthetics in a model of experimental pain.

Methods: In a first experimental trial, participants (n = 12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg [middle dot]-1 [middle dot] h-1 for another 50 min). In a second trial, modified intravenous regional anesthesia was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in their other arm, 40 ml NaCl, 0.9%, served as a control. In both trials, calibrated tonic and phasic mechanical and chemical (histamine) stimuli were applied to determine differentially the impairment of tactile and nociceptive perception.

Results: Mechanical sensitivity to touch, phasic mechanical stimuli of noxious intensity, and heat pain thresholds remained unchanged after systemic and regional application of the anesthetic. In contrast, histamine-induced itch (intravenous regional anesthesia), axon reflex flare (systemic treatment), and development of acute mechanical hyperalgesia during tonic pressure (12 N; 2 min) of an interdigital web was significantly suppressed after both treatments.     

7种常用静脉麻醉药对血流动力学影响的比较

比较常用静脉麻醉药对血流动力学的影响。方法：８０９例拟行全麻醉患者随机分成八组,分别给予生理盐水１０ｍｌ、硫喷妥钠６ｍｇ／ｋｇ、异丙酚２．５ｍｇ／ｋｇ咪唑安定０．３ｍｇ／ｋｇ,依托咪酯丙二醇制剂０．３ｍｇ／ｋｇ,依托咪酯乳剂０．３ｍｇ／ｋｇ、氯胺酮２ｍｇ／ｋｇ和芬太尼５μｇ／ｋｇ。用Ｕｌｔｉｍａ监测仪和阻抗法记录并计算血液动力学有关参数。结果：ＢＰ而言,其降幅排序为异丙酚〉咪唑安定〉硫喷妥钠〉硫喷     

Platelet Consumption by Arterial Prostheses: The Effects of Endothelialization and Pharmacologic Inhibition of Platelet Function

The thrombogenic mechanism of arterial grafts has been studied by determining the relative utilization of platelets, fibrinogen and plasminogen by human arterial prostheses, and by direct examination of arterial grafts in a baboon model. Forty-one survival and turnover measurements of (51)Crplatelets, (131)I-fibrinogen and (125)I-plasminogen in ten patients with aortofemoral knitted Dacron prostheses demonstrated platelet consumption after graft placement (platelet survival 4.2 days +/- 0.5 and turnover 68,000 plat/ul/day +/-10,000 compared with 8.2 days +/- 0.3 and 35,000 plat/ul/day +/- 5,000 respectively for control subjects with stable vascular disease, p < 0.01). In vitro platelet function test results were normal. Platelet consumption was interrupted by dipyridamole or a combination of dipyridamole and acetylsalicylic acid, and platelet survival normalized spontaneously during nine months postoperatively. No significantly increased consumption of fibrinogen or plasminogen was found in these patients with arterial grafts.Placement of impervious knitted Dacron velour aortic grafts in baboons reproduced platelet consumption that progressively normalized over six weeks postoperatively. Platelet survival measurements correlated directly with endothelial cell coverage of the graft luminal surface in these animals implying that endothelialization of the graft surface was also occurring postoperatively in patients.     

Effects of Intravenous Aspirin on Prostaglandin Synthesis and Kidney Function in Intensive Care Patients

The effects of intravenous acetylsalicylic acid (1.0 g bolus)on renal function and prostaglandin synthesis were evaluatedin a prospective, controlled study in eight patients in an intensivecare unit. Four of these patients had congestive heart failure.Administration of acetylsalicylic acid caused significant antidiuresis(–56%), antinatriuresis (–82%), renin suppression(–26%) and decreased GFR (–41%). All of these changeswere completely reversible within 1–2 hours and tendedto be more pronounced in the patients with congestive heartfailure. Urinary excretion of prostaglandin E was depressedprofoundly (–93%) and did not return to more than 45%of control 6 h after the administration of acetylsalicylic acid. We conclude that intravenous acetylsalicylic acid affects kidneyfunction in a manner similar to other prostaglandin synthesisinhibitors. Its effects are, however, short-lived. The inhibitionof urinary PGE₂ excretion outlasts GFR depression, antidiuresis,antinatriuresis and renin suppression by several hours.     

Combined Aspirin and Cilostazol Treatment is Associated with Reduced Platelet Aggregation and Prevention of Exercise-Induced Platelet Activation

BackgroundCilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise.MethodsNineteen claudicants completed a double-blind, randomised, controlled, cross-over trial. Each subject received a 2-week course of aspirin (75 mg) and placebo and aspirin and cilostazol (100 mg twice daily). Following each 2-week treatment period, patients participated in a standardised treadmill test (3.2 km h^?1, 10° incline) walking to maximal claudication distance. The exercise was repeated thrice in total, and blood was sampled before and after exercise. Platelet activation was measured using free platelet counting aggregation, flow cytometry for surface markers of platelet activation and soluble P-selectin assay.ResultsCompared to aspirin and placebo, combination treatment with aspirin and cilostazol was associated with reduced arachidonic-acid-induced platelet aggregation (p < 0.01, Wilcoxon signed-rank test). Aspirin and placebo treatment were associated with elevated P-selectin expression, platelet-monocyte aggregation and reduced CD42b expression (p < 0.05, Wilcoxon signed-rank test) post-exercise. No difference was seen in spontaneous platelet aggregation whilst soluble P-selectin was reduced post-exercise with combination treatment with aspirin and cilostazol (p < 0.05, Wilcoxon signed-rank test).ConclusionsCombination treatment with aspirin and cilostazol results in suppression of platelet activation and reduces the effect of exercise on platelets. The benefit seen may be a result of cilostazol enhancing the inhibitory effect of aspirin on the cyclo-oxygenase pathway.     

比较七氟醚、异氟醚和安氟醚对颅内压的影响

目的：为了观察七氟醚对颅内压的影响。方法：选择２４例颅内肿胶病人,测定七氟醚麻醉的时颅内压变化并与异氟醚和安氟醚进行比较。术前用药、麻醉诱导及维持的静脉用药相同。于Ｌ３－４穿刺蛛网膜睛腔测脑脊液压（代表颅内压,ＩＣＰ）。依吸入药不同随机分为七的氟醚（Ｓ）组,异氟醚（１）组和安氟醚（Ｅ）组,监测ＢＰ、ＭＡＰ、ＥＣＧ、ＳｐＯ２、ＰＥＴ、ＣＯ２和ＭＡＣ,调整ＶＴ和ＲＲａＣＯ２维持在４～４．６６ＫＰＡ。三     

The Effects of Fiberoptic Bronchoscopy With and Without Atropine Premedication on Pulmonary Function in Humans

Pulmonary function studies, including arterial blood gas analysis, were performed in 21 patients undergoing fiberoptic bronchoscopy. Eight received premedication with atropine and 13 did not. In the atropine-treated group there was no significant deterioration in pulmonary function immediately after bronchoscopy compared with baseline. Compared with the values obtained after topical lidocaine anesthesia, however, there was a decrease in peak expiratory flow rate (PEFR) (20 ± 20%), forced expiratory volume in one second (FEV_1.0) (11 ± 12%), forced expiratory flow between 25 and 75% of vital capacity (FEF_25–75) (22 ± 16%), and forced expiratory flow at 75% of exhaled vital capacity (FEF₇₅) (28 ± 38%) and an increase in residual volume (RV) (16 ± 19%). In the no-atropine group, postbronchoscopy values showed a decrease in PEFR (13 ± 19%), forced vital capacity (FVC) (13 ± 19%), FEV_1.0 (14 ± 16%), and oxygen partial pressure (Pa_O2) (11 ± 9%) and an increase in RV (19 ± 31%) and alveolar-arterial oxygen pressure gradient (ΔaaPo₂) (91 ± 129%) compared with baseline values. In this group also, topical lidocaine anesthesia resulted in a decrease in FVC compared with baseline. We conclude that the deleterious effect of bronchoscopy on pulmonary function is counterbalanced by the beneficial effect of atropine and that atropine is therefore a useful premedication for fiberoptic bronchoscopy.     

Effects of Propofol on H-reflex in Humans

Background: Depression of spinal cord motoneuron excitability has been proposed to contribute to surgical immobility. The H-reflex, which measures [alpha]-motoneuron excitability, is depressed by volatile anesthetics, whereas the action of propofol is unknown. The objective of this study was to determine the effects of propofol anesthesia on the H-reflex.

Methods: In 13 patients (group 1), H-reflex was measured before (T0), 3 min after (T1), and 10 min after (T2) a 2-mg/kg bolus dose of propofol, followed by an infusion of 10 mg [middle dot] kg-1 [middle dot] h-1. Ten patients (group 2) were studied when propofol was given via a programmable pump set to a propofol blood concentration of 6 [mu]g/ml, and 10 patients (group 3) were studied with the pump set to 9 [mu]g/ml. Latencies and amplitudes of H-reflexes (H0, H1, H2) and M-responses (M0, M1, M2) of the soleus muscle were recorded, and H/M ratios (H0/M0, H1/M1, H2/M2) were calculated.

Results: In group 1, H-reflex amplitudes and the H/M ratio were diminished after induction with propofol (H0vs. H1, P = 0.033; H0/M0vs. H1/M1, P = 0.042). After 10 min of propofol infusion, the H2/M2 ratio was still decreased versus H0/M0 (P = 0.031). In group 2, no difference was detected. In group 3, propofol depressed H-reflex amplitudes at T2 (H0vs. H2, P < 0.01), and amplitudes were also lower at T2 than at T1 (H1vs. H2, P < 0.01). In this group, the H/M ratio decreased from T0 to T2 (H0/M0vs. H2/M2, P < 0.002).     

Effects of Hyperventilation and Hypocapnic/Normocapnic Hypoxemia on Renal Function and Lithium Clearance in Humans

Background: Using the renal clearance of lithium as an index of proximal tubular outflow, this study tested the hypothesis that acute hypocapnic hypoxemia decreases proximal tubular reabsorption to the same extent as hypocapnic normoxemia (hyperventilation) and that this response is blunted during normocapnic hypoxemia.

Methods: Eight persons were studied on five occasions: (1) during inhalation of 10% oxygen (hypocapnic hypoxemia), (2) during hyperventilation of room air leading to carbon dioxide values similar to those with hypocapnic hypoxemia, (3) during inhalation of 10% oxygen with the addition of carbon dioxide to produce normocapnia, (4) during normal breathing of room air through the same tight-fitting face mask as used on the other study days, and (5) during breathing of room air without the face mask.

Results: Hypocapnic and normocapnic hypoxemia and hyperventilation increased cardiac output, respiratory minute volume, and effective renal plasma flow. Glomerular filtration rate remained unchanged on all study days. Calculated proximal tubular reabsorption decreased during hypocapnic hypoxemia and hyperventilation but remained unchanged with normocapnic hypoxemia. Sodium clearance increased slightly during hypocapnic and normocapnic hypoxemia, hyperventilation, and normocapnic normoxemia with but not without the face mask.     

A Comparison of the Effects of Membrane and Bubble Oxygenators on Platelet Counts and Platelet Size in Elective Cardiac Operations

To compare the effects of membrane and bubble oxygenators on platelet counts and the size of circulating platelets, serial hematocrits, platelet counts, and platelet sizing were measured in 23 patients undergoing elective cardiac operations. In 10 patients a bubble oxygenator was used and in 13, a SciMed membrane oxygenator. The two groups were statistically similar with respect to age, weight, time on bypass, and mean blood flow rates during bypass.It was found that platelet counts, when corrected for hemodilution, did not fall from control levels during or up to 24 hours after cardiopulmonary bypass in either group. In both groups, the relative number of platelets per gram of hemoglobin increased slightly during and after bypass, and this increase was significant in the bubble oxygenator group. The average size of circulating platelets increased only in the bubble oxygenator group, and then only in the one-day postoperative sample. These findings suggest that the membrane oxygenator offers no advantage with respect to preservation of platelets during cardiopulmonary bypass lasting up to 2 to 3 hours.     

Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans

The aim of this study was to determine the effects of single and repeated episodes of clamped hypoglycemia on fibrinolytic balance, proinflammatory biomarkers, proatherothrombotic mechanisms, and endothelial function. Twenty healthy individuals (12 male and 8 female) were studied during separate 2-day randomized protocols. Day 1 consisted of either two 2-h hyperinsulinemic (812 ± 50 pmol/L)-euglycemic (5 ± 0.1 mmol/L) or hyperinsulinemic (812 ± 50 pmol/L)-hypoglycemic (2.9 ± 0.1 mmol/L) clamps. Day 2 consisted of a single 2-h hyperinsulinemic-hypoglycemic clamp. Two-dimensional Doppler ultrasound was used to determine brachial arterial endothelial function. Plasminogen activator inhibitor 1, vascular cell adhesion molecule-1, intracellular adhesion molecule-1, E-selectin, P-selectin, TAT (thrombin/antithrombin complex), tumor necrosis factor-α, and interleukin-6 responses were increased (P < 0.05) during single or repeated hypoglycemia compared with euglycemia. Endogenous and exogenous nitric oxide (NO)-mediated vasodilation were both impaired by repeated hypoglycemia. Neuroendocrine and autonomic nervous system (ANS) responses were also blunted by repeated hypoglycemia (P < 0.05). In summary, acute moderate hypoglycemia impairs fibrinolytic balance; increases proinflammatory responses, platelet activation, and coagulation biomarkers; and reduces NO-mediated endothelial function in healthy individuals. Repeated episodes of hypoglycemia further impair vascular function by additionally reducing exogenously NO-mediated endothelial function and increasing coagulation biomarkers. We conclude that despite reduced neuroendocrine and ANS responses, antecedent hypoglycemia results in greater endothelial dysfunction and an increased proatherothrombotic state compared with a single acute episode of hypoglycemia.     

Platelet Function During Cardiopulmonary Bypass Using Multiple Electrode Aggregometry: Comparison of Centrifugal and Roller Pumps

Blood trauma may be lower with centrifugal pumps (CPs) than with roller pumps (RPs) during cardiopulmonary bypass (CPB), because, unlike RPs, CPs do not compress the tubing, and shear stress is considered lower in CPs than in RPs. However, relative platelet function remains unclear. Using multiple electrode aggregometry (MEA), we compared platelet function with CP and RP. Ten swine underwent CPB for 3 h, with five weaned off using CP and five using RP. Platelet function was measured using MEA, as were hemoglobin concentration and platelet count, before sternotomy, after heparin infusion, 30 min and 3 h after starting CPB, after protamine infusion, and 60 min after stopping CPB. Platelet activation was initiated with adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor‐activating protein 6 (TRAP). Fibrinogen, platelet factor 4 (PF4), and β‐thromboglobin (β‐TG) concentrations were measured before sternotomy and 60 min after stopping CPB. In the CP group and using ADP, aggregation was significantly reduced 30 min (P = 0.019) and 3 h (P = 0.027) after starting CPB, recovering to baseline 60 min after CPB was stopped. In the RP group, aggregation was significantly decreased 30 min (P = 0.007) and 3 h (P = 0.003) after starting CPB and after protamine administration (P = 0.028). With AA, aggregation significantly decreased 30 min after starting CPB in both the CP (P = 0.012) and RP (P = 0.016) groups, slightly increasing 3 h after starting CPB and after protamine infusion, and recovering to baseline 60 min after CPB cessation. With TRAP, aggregation in the CP and RP groups decreased 30 min after starting the pump, although changes were not significant; aggregation gradually recovered after 3 h and returned to baseline 60 min after the pumps were stopped. There were no significant differences at all sampling points of MEA. In both groups, fibrinogen, PF4, and β‐TG concentrations were similar 60 min after pump cessation and before sternotomy. Platelet function, evaluated with MEA, was lowest 30 min after CPB was started but did not decrease over time in either group. As assessed by MEA, platelet function using CP and RP did not differ significantly. Platelet dysfunction was caused mainly by initial contact with foreign materials and may not be dependent on type of pump.     

阿屈可林对眼内压影响的临床观察

观察全麻时阿屈可林和琥珀胆碱对眼内压的影响，结果表明，阿屈可林对眼内压无影响，而琥珀胆碱增加眼内压，提示对患有青光眼的病人进行全麻时，阿屈可林是一种较好的选择。     

Platelet Function in Acute Experimental Pancreatitis

Acute pancreatitis (AP) is characterized by disturbances of pancreatic microcirculation. It remains unclear whether platelets contribute to these perfusion disturbances. The aim of our study was to investigate platelet activation and function in experimental AP. Acute pancreatitis was induced in rats: (1) control (n = 18; Ringer’s solution), (2) mild AP (n = 18; cerulein), and (3) severe AP (n = 18; glycodeoxycholic acid (GDOC) + cerulein). After 12 h, intravital microscopy was performed. Rhodamine-stained platelets were used to investigate velocity and endothelial adhesion in capillaries and venules. In addition, erythrocyte velocity and leukocyte adhesion were evaluated. Serum amylase, thromboxane A2, and histology were evaluated after 24 h in additional animals of each group. Results showed that 24 h after cerulein application, histology exhibited a mild AP, whereas GDOC induced severe necrotizing AP. Intravital microscopy showed significantly more platelet–endothelium interaction, reduced erythrocyte velocity, and increased leukocyte adherence in animals with AP compared to control animals. Thromboxane levels were significantly elevated in all AP animals and correlated with the extent of platelet activation and severity of AP. In conclusion, platelet activation plays an important role in acute, especially necrotizing, pancreatitis. Mainly temporary platelet–endothelium interaction is observed during mild AP, whereas severe AP is characterized by firm adhesion with consecutive coagulatory activation and perfusion failure. Parts of the results of this study were presented at the congress of the German Surgical Society, Berlin (May 2004), the Digestive Disease Week (May 2004), and the Annual Meeting of the American Pancreatic Association, Chicago (November 2004).     

体外循环对血小板功能影响的研究

选择心脏瓣膜替换术病人１０例，用流式细胞术（ＦＣＭ）方法在围术期定量检测血小板质膜蛋白Ｉｂ、ＩＩｂ／ＩＩａ复合物、血小板α颗粒膜蛋白、溶酶体完整膜蛋白－ＣＤ６３及血小板计数等项血小板膜糖蛋白指标进行统计学处理。结果表明体外循环中血小板计数、膜糖蛋白Ｉｂ均明显下降；α－颗粒膜蛋白１４０、溶酶体完整膜蛋白及膜糖蛋白Ｉｂ／ＩＩａ均显著增高。证实体外循环（ＣＰＢ）对血小板膜糖蛋白的影响，更深入了解ＣＰＢ导致血小板功能获得性损害的分子机制。     

Endothelial Function and Weight Loss in Obese Humans

Background: Obesity is a major risk factor for the development of endothelial dysfunction. We explored the effect of different degrees of body mass on endothelial function, lipids, systemic inflammation and glucose homeostasis and the effect of surgically-induced weight loss on endothelial function in severely obese humans. Methods: A cross-sectional study of healthy subjects across a wide range of body fatness was performed to characterize the effect of obesity on flow-mediated dilatation (FMD), systemic inflammation, blood pressure and insulin sensitivity. A longitudinal study was performed to assess the effect of bariatric surgery induced weight loss on these parameters. 73 healthy subjects across a wide range of body mass were recruited; of these, 8 underwent bariatric surgery (median BMI 52.2 kg/m², interquartile range 50.355.9). Endothelial dependent vasodilatation was measured using the brachial artery vasodilatory response to forearm hyperemia assessed using highresolution ultrasonography. Results: Obese subjects were characterised by a complex collection of abnormalities, with hypertension, impaired glucose homeostasis, systemic inflammation and reduced FMD. BMI ≤25 kg/m² (median FMD 9.7%, interquartile range 6.8-12.2), BMI >30 kg/m² (median FMD 6.7% 4.8-7.5), P=0.01 comparing FMD in lean and obese subjects. A mean reduction in weight of 23.4 (4.6) kg produced an improvement in FMD from 5.3% (3.87.0) to 10.2% (7.6-13.3), P=0.01. Conclusions: Even moderate obesity leads to endothelial dysfunction. In severely obese subjects, FMD is normalized by weight loss. This improvement in FMD is associated with a decline in inflammatory markers, blood pressure and insulin. The improvement in FMD occurred despite patients remaining significantly obese. These results suggest that an integrated approach to improving endothelial function in obese humans may be necessary.