Thoracic epidural analgesia augments ileal mucosal capillary perfusion and improves survival in severe acute pancreatitis in rats

BACKGROUND: Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats. METHODS: Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia. RESULTS: In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05). CONCLUSION: Thoracic epidural analgesia attenuated systemic response and improved survival in severe acute pancreatitis. These effects might be explained by improved mucosal perfusion.     

Thoracic epidural anesthesia increases mucosal perfusion in ileum of rats

BACKGROUND: Previous studies reported that thoracic epidural anesthesia (TEA) protected against a decrease in gastric intramucosal pH, suggesting that TEA increased gut mucosal perfusion. The current study examines the effects of TEA on ileal mucosa using intravital microscopy in anesthetized rats. METHODS: Nineteen rats were equipped with epidural catheters, with the tip placed at T7 through T9. Rats were anesthetized and mechanically ventilated. After midline abdominal incision, the ileum was prepared for intravital microscopy. Videomicroscopy on the ileal mucosa was performed before and after epidural infusion of 20 microliter of bupivacaine 0.4% (TEA group, n = 11 rats) or normal saline (control group, n = 8 rats). Microvascular blood flow in ileum mucosa was assessed offline using computerized image analysis. RESULTS: Control rats exhibited unchanged mean arterial pressure and microvascular perfusion. During TEA, mean arterial pressure was decreased compared with the control group (93 +/- 10 vs. 105 +/- 9 mmHg; P < 0.05). Epidural bupivacaine increased red cell velocity in terminal arterioles from 888 +/- 202 to 1,215 +/- 268 micrometer/s (control, 793 +/- 250 to 741 +/- 195 micrometer/s; P < 0.001 between groups). Because arteriolar diameter was not affected, this increase in red cell velocity may represent an increase in arteriolar blood flow. Total intercapillary area (inversely related to perfused capillary density) was unchanged, but for the TEA group the difference between total intercapillary area and the intercapillary area calculated for continuously perfused capillaries was decreased compared with the control group (16 +/- 12 vs. 40 +/- 19%; P < 0.001), indicating a decrease in intermittent (stop-and-go) blood flow in the villus microcirculation. CONCLUSION: Thoracic epidural anesthesia increased gut mucosal blood flow and reduced intermittent flow in the villus microcirculation in the presence of a decreased perfusion pressure.     

Thoracic Epidural Anesthesia Increases Mucosal Perfusion in Ileum of Rats

Background: Previous studies reported that thoracic epidural anesthesia (TEA) protected against a decrease in gastric intramucosal pH, suggesting that TEA increased gut mucosal perfusion. The current study examines the effects of TEA on ileal mucosa using intravital microscopy in anesthetized rats.

Methods: Nineteen rats were equipped with epidural catheters, with the tip placed at T7 through T9. Rats were anesthetized and mechanically ventilated. After midline abdominal incision, the ileum was prepared for intravital microscopy. Videomicroscopy on the ileal mucosa was performed before and after epidural infusion of 20 [mu]l of bupivacaine 0.4% (TEA group, n = 11 rats) or normal saline (control group, n = 8 rats). Microvascular blood flow in ileum mucosa was assessed offline using computerized image analysis.

Results: Control rats exhibited unchanged mean arterial pressure and microvascular perfusion. During TEA, mean arterial pressure was decreased compared with the control group (93 +/- 10 vs. 105 +/- 9 mmHg;P < 0.05). Epidural bupivacaine increased red cell velocity in terminal arterioles from 888 +/- 202 to 1,215 +/- 268 [mu]m/s (control, 793 +/- 250 to 741 +/- 195 [mu]m/s;P < 0.001 between groups). Because arteriolar diameter was not affected, this increase in red cell velocity may represent an increase in arteriolar blood flow. Total intercapillary area (inversely related to perfused capillary density) was unchanged, but for the TEA group the difference between total intercapillary area and the intercapillary area calculated for continuously perfused capillaries was decreased compared with the control group (16 +/- 12 vs. 40 +/- 19%;P < 0.001), indicating a decrease in intermittent (stop-and-go) blood flow in the villus microcirculation.     

Epidural analgesia prevents endotoxin-induced gut mucosal injury in rabbits

In the present study, we evaluated the effect of epidural analgesia on the alterations of gut barrier function elicited by endotoxin in rabbits. After the placement of an epidural catheter, 28 male rabbits were randomized into either 0.5% lidocaine (group E) or saline (group C) group. The solutions (0.4 mL/kg) were epidurally injected, followed by continuous infusion (0.1 mL . kg(-1) . h(-1)) throughout the study period. Under a continuous infusion of lipopolysaccharide (15 microg . kg(-1) . h(-1)), mean arterial blood pressure, intramucosal pH, and plasma thrombomodulin concentrations were measured. At 4 h, mean arterial blood pressure was lower (P < 0.05), intramucosal pH was higher (P < 0.01), and the progression of hemodilution more profound (P < 0.05) in group E versus group C, whereas plasma thrombomodulin levels were increased to a similar extent between the groups. With less wet-to-dry weight ratio of ileum, histopathological injury scores of gut mucosa were significantly less in group E versus group C (P < 0.01). In a separate series of experiments (n = 10 each group), mucosal permeability in group E was significantly less compared with group C (P < 0.05). Collectively, these studies showed that despite a significant decrease of perfusion pressure and arterial oxygen content, epidural analgesia minimized endotoxin-induced functional and structural injury of gut mucosa possibly through endothelium-independent mechanisms.     

Intestinal microcirculation and gut permeability in acute pancreatitis: Early changes and therapeutic implications

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl-min^−l.cap ⁻¹ [control]; P = NS), whereas mucosal (1.59 _± 0.03 vs. 2.28 ± 0.03 nl.min^−l.cap ⁻¹ [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl-min^−l.cap ^-1 [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 = 0.03 vs. 1.98 ± 0.04 nl’min^-1.cap ^-1 [control]; P <0.01) and colonic (mucosal: 0.59 = 0.01 vs. 2.28 ± 0.03 nl.min^−l.cap ^-1 [control], P < 0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl.min^−l.cap ^-1 [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ±19 nmol.hr^−l.cm {−2}2; mild pancreatitis: 158±23 nmol-hr^−l.cm^-2; severe pancreatitis: 181 ±33 nmol.hr^−l.cm^-2; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 19–22, 1996. Supported in part by Deutsche Forschungsgemeinschaft (DFG Fo 197/3).     

Evidence for the role of reactive nitrogen species in polymicrobial sepsis-induced renal peritubular capillary dysfunction and tubular injury

Acute kidney injury (AKI) remains a frequent and serious complication of human sepsis that contributes significantly to mortality. For better understanding of the development of AKI during sepsis, the cecal ligation and puncture (CLP) murine model of sepsis was studied using intravital video microscopy (IVVM) of the kidney. IVVM with FITC-dextran was used to determine the percentage of capillaries with continuous, intermittent or no flow at 0 (sham), 10, 16, and 22 h after CLP. There was a dramatic fall in capillary perfusion as early as 10 h after CLP that persisted through 22 h. The percentage of vessels with continuous flow at 16 h decreased from 73 +/- 2% in shams to 16 +/- 2% (P < 0.05), whereas the percentage of vessels with no flow increased from 4 +/- 1% in shams to 42 +/- 2% (P < 0.05). The capillary perfusion defect preceded the rise in serum creatinine. IVVM with dihydrorhodamine-123 was used to quantify in real time reactive nitrogen species (RNS) generation by renal tubules, and the inducible nitric oxide synthase inhibitor L-iminoethyl-lysine (mg/kg) was used to examine the role of inducible nitric oxide synthase inhibitor on capillary dysfunction and RNS generation. Tubular generation of RNS was significantly elevated at 10 h after CLP and was associated with tubules that were bordered by capillaries with reduced perfusion. L-iminoethyl-lysine significantly reversed the capillary perfusion defect, blocked RNS generation, and reduced AKI. These data show that capillary dysfunction and RNS generation contribute to tubular injury and suggest that RNS should be considered a potential therapeutic target in the treatment of sepsis-induced AKI.     

Thoracic Epidural Anesthesia Attenuates Hemorrhage-induced Impairment of Intestinal Perfusion in Rats

Background: During hemorrhagic hypotension, sympathetic vasoconstriction crucially contributes to gut mucosal damage. Sympathetic blockade by thoracic epidural anesthesia has been shown to increase mucosal microvascular perfusion and to improve survival after severe hemorrhage in laboratory animals. This study investigates the effects of thoracic epidural anesthesia on intestinal microvascular perfusion during hemorrhagic hypotension in rats.

Methods: In 32 anesthetized Sprague-Dawley rats either lidocaine 2% (thoracic epidural anesthesia) or normal saline (control) was infused via thoracic epidural catheters. Hemorrhagic hypotension (mean arterial pressure 30 mmHg for 60 min) was induced by withdrawal of blood, which was subsequently retransfused for resuscitation. Functional capillary density and erythrocyte velocity in the mucosa and muscularis were determined by intravital microscopy. Leukocyte-endothelium interaction was studied in postcapillary venules and sympathetic nerve fibers of the intestinal wall were identified by immunohistochemistry.

Results: During hypotension functional capillary density was significantly (P < 0.001) lower in the muscularis of the control group (median [25/75 percentile]: -46.5% [-59.6/-20.8%] change from baseline) as compared with animals that received thoracic epidural anesthesia (-6.1% [-13.4/1.1%]). There were no differences in erythrocyte velocity between groups throughout the experiment. Leukocyte rolling increased significantly (P < 0.001) after resuscitation in control (12 [6/15]vs. baseline 2.5 [1/8]) but not in thoracic epidural anesthesia (4 [2.3/7]vs. baseline: 5 [3/15.5]). Sympathetic nerve fibers were identified in the muscularis and submucosa but not in the mucosa.     

Thoracic epidural anesthesia attenuates hemorrhage-induced impairment of intestinal perfusion in rats

BACKGROUND: During hemorrhagic hypotension, sympathetic vasoconstriction crucially contributes to gut mucosal damage. Sympathetic blockade by thoracic epidural anesthesia has been shown to increase mucosal microvascular perfusion and to improve survival after severe hemorrhage in laboratory animals. This study investigates the effects of thoracic epidural anesthesia on intestinal microvascular perfusion during hemorrhagic hypotension in rats. METHODS: In 32 anesthetized Sprague-Dawley rats either lidocaine 2% (thoracic epidural anesthesia) or normal saline (control) was infused via thoracic epidural catheters. Hemorrhagic hypotension (mean arterial pressure 30 mmHg for 60 min) was induced by withdrawal of blood, which was subsequently retransfused for resuscitation. Functional capillary density and erythrocyte velocity in the mucosa and muscularis were determined by intravital microscopy. Leukocyte-endothelium interaction was studied in postcapillary venules and sympathetic nerve fibers of the intestinal wall were identified by immunohistochemistry. RESULTS: During hypotension functional capillary density was significantly (P < 0.001) lower in the muscularis of the control group (median [25/75 percentile]: -46.5% [-59.6/-20.8%] change from baseline) as compared with animals that received thoracic epidural anesthesia (-6.1% [-13.4/1.1%]). There were no differences in erythrocyte velocity between groups throughout the experiment. Leukocyte rolling increased significantly (P < 0.001) after resuscitation in control (12 [6/15] vs. baseline 2.5 [1/8]) but not in thoracic epidural anesthesia (4 [2.3/7] vs. baseline: 5 [3/15.5]). Sympathetic nerve fibers were identified in the muscularis and submucosa but not in the mucosa. CONCLUSIONS: During hemorrhagic hypotension and after resuscitation, thoracic epidural anesthesia has beneficial effects on intestinal microvascular perfusion. Because of blockade of sympathetic nerves, thoracic epidural anesthesia prevents perfusion impairment of the muscularis during hypotension and attenuates leukocyte rolling after resuscitation.     

布比卡因、罗哌卡因与芬太尼不同配伍用于连续术后硬膜外镇痛安全性探讨

目的探讨布比卡因、罗哌卡因与芬太尼不同配伍用于连续术后硬膜外镇痛的效果、并发症及安全陛。方法1600例行连续术后硬膜外镇痛的患者,按所用镇痛药物配伍不同分为：0．1％布比卡因＋5μg／ml芬太尼组（B组,n=920）和0．2％罗哌卡因＋2μg／ml芬太尼组（R组,n=680）。对两组镇痛效果（视觉模拟评分及患者对镇痛效果的满意度）、并发症和处理措施进行总结分析。结果视觉模拟评分两组无差异（P〉0．05）。患者对镇痛的满意度R组明显高于B组（P〉0．05）。并发症的发生率B组高于R组（P〉0．05）。两组内年龄≥60岁的患者低血压的发生率高于年龄〈60岁者（P〈0．05）;女性患者恶心呕吐的发生率高于男性（P〈0．05）;腰段硬膜外镇痛患者下肢乏力或麻木的发生率明显高于胸段硬膜外镇痛患者（P〈0．05）。结论布比卡因、罗哌卡因与芬太尼不同配伍均可安全有效地用于连续术后硬膜外镇痛,罗哌卡因组并发症较少,并发症的发生与镇痛药物、年龄、性别及硬膜外置管部位有关。     

Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis.

Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.     

Oleic acid induced pancreatitis in pigs

An experimental model of edematous pancreatitis in pigs was established and measurement of pancreatic macro- and microcirculatory parameters and determinations of pancreatic enzymes (lipase, phospholipase A) and vasoactive mediators (prostanoids, kallikrein, kininogen) were performed. During general anesthesia the pancreas was isolated in situ. Pancreatic microcirculatory parameters were measured using videofluorescence microscopy after iv administration of FITC-Dextran. In hourly collected samples lipase and phospholipase A activities were determined enzymatically, concentrations of kallikrein, kininogen, and selected prostanoids were measured by radioimmunoassay. Two experimental groups were studied: (1) control (n = 9); (2) edematous pancreatitis induced by injection of oleic acid into the pancreatic artery (free fatty acid, ffa; n = 10). The animals were followed up for 6 hr. Systemic hemodynamic parameters remained constant in both groups. In the pancreatitis group pancreatic blood flow and O2-consumption decreased significantly (-55 and -49%), while pancreatic vascular resistance increased significantly (+50%). During baseline conditions 41% of all capillaries were perfused. In the pancreatitis group there were both areas with persistent stasis as well as areas with continuous perfusion. However, in the latter areas the portion of perfused capillaries decreased significantly to 27%. In the control group the portion of perfused capillaries remained constant. Liberation of lipase and phospholipase A especially into lymph and ascites fluid was measured during pancreatitis. Furthermore, considerable releases of kallikrein into lymph (+50%) and ascites (+800%) and a marked consumption of kininogen in lymph (+90%) and in ascites fluid (+80%) were measured. Activation of the arachidonic acid cascade and a significant release of prostacyclin and thromboxane A2 into pancreatic venous blood and lymph was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local shockwave-induced capillary recruitment improves survival of musculocutaneous flaps

Background

Shockwave (SW) application has been shown to limit flap necrosis. However, the underlying microhemodynamic mechanisms remain unclear. Therefore, the objective of this study was to analyze the effect of SW application on a microcirculatory level.

Methods

We treated 12 C57BL/6 mice with local SW application (500 shockwave impulses at 0.15 mJ/mm²) either 24 h before (preconditioning [PRE]) or 30 min after (postconditioning [POST]) flap elevation. Animals with an untreated flap (CON) or without a flap served as controls. We applied dorsal skinfold chambers to the animals and performed epifluorescence microscopy over a 10-d period to assess microcirculatory parameters (arteriolar diameter, red blood cell velocity, blood flow, functional capillary density, and intercapillary distance) as well as inflammation, apoptotic cell death, and necrosis.

Results

SW application significantly decreased tissue necrosis independently of the application time point (PRE: 29% ± 7%; POST: 25% ± 7% versus CON: 47% ± 2%; day 10, P < 0.05). Arteriolar diameter, red blood cell velocity, and blood flow were not statistically significantly different among the 3 flap groups. However, SW (PRE and POST) resulted in an early and persistent increase in functional capillary density and consequently decreased intercapillary distance compared with CON and the group without a flap (P < 0.05). Also, SW resulted in a significantly decreased inflammatory response (P < 0.05) and induced an angiogenic response, as indicated by new functional microvessel formation observed 5 d after therapy.

Conclusions

Local SW application improved tissue survival by recruitment of sleeping capillaries within the non ischemic tissue and maintenance of capillary perfusion within the critically perfused tissue after induction of ischemia, which was independent of the application time point. Neoangiogenesis occurred beyond the ischemic tolerance of the tissue, and therefore does not seem to contribute to improved tissue survival.     

Cardiopulmonary bypass in humans--jejunal mucosal perfusion increases in parallel with well-maintained microvascular hematocrit

BACKGROUND: An imbalance between splanchnic oxygen supply and demand occurs during cardiopulmonary bypass (CPB) in man, which might disrupt the intestinal mucosal barrier function. The aim of the present study was to evaluate the effects of mild hypothermic CPB on intestinal mucosal perfusion in man undergoing cardiac surgery. Additionally we aimed to identify variables, which independently could predict changes of intestinal mucosal microcirculatory variables during CPB. METHODS: Jejunal mucosal perfusion (JMP), jejunal mucosal hematocrit (JMHt), red blood cell (RBC) velocity and arteriolar vasomotion using endoluminal jejunal laser Doppler flow metry were studied in eight cardiac surgical patients before and during CPB at a temperature of 34 degrees C. RESULTS: Cardiopulmonary bypass and the accompanied hemodilution (25-30%) induced a 44% increase in JMP (P < 0.05) and a 42% increase in RBC velocity (P < 0.01), with no change in JMHt. The oscillation amplitude of JMP, at a fundamental frequency of 2.8 cycles min(-1), increased with 175% (P < 0.05) during CPB. Splanchnic oxygen extraction increased by 64% during CPB (P < 0.05). Stepwise multiple regression analysis identified systemic hematocrit, arterial O2 and CO2 tension and splanchnic oxygen extraction as independent predictors of RBC velocity during CPB (R2=0.63, P < 0.001). The oscillation amplitude of JMP was predicted by RBC velocity and splanchnic oxygen extraction (R2= 0.68, P <0.0001). CONCLUSIONS: The increase in RBC velocity and enhanced arteriolar vasomotion, as well as maintained jejunal mucosal hematocrit, are microcirculatory, compensatory mechanisms for the splanchic oxygen supply/demand mismatch seen during cardiopulmonary bypass in humans.     

Automated regular boluses for epidural analgesia: a comparison with continuous infusion

BACKGROUND: Intermittent epidural bolus dosing is a method of drug delivery that can prolong the duration of labour analgesia induced by a combined spinal epidural (CSE). In this randomized, double-blinded study, we compared the analgesic efficacy of two drug delivery systems: regular intermittent epidural boluses and continuous epidural infusion and assessed the incidence of breakthrough pain after CSE. METHODS: With the approval of the Hospital Ethics Committee, we recruited 60 parturients into this randomized controlled trial. A CSE was performed with intrathecal fentanyl 25 mug in all patients. The parturients were then randomly allocated into two groups. The infusion group received a continuous epidural infusion of levobupivacaine 0.1% with fentanyl 2 microg/mL at a rate of 10 mL/h. The bolus group received 5-mL epidural boluses every half hour. The sample size was computed to detect a 40% reduction in the rate of breakthrough pain. RESULTS: The bolus group had a lower incidence of breakthrough pain than the infusion group (10% vs. 37%, P < 0.05). The bolus group also had significantly higher satisfaction scores for labour analgesia: 97+/-8 (mean+/-SD) vs. 89+/-7 (P < 0.05). CONCLUSION: Automated regular bolus delivery of epidural analgesia when compared with continuous infusion decreased the incidence of breakthrough pain and increased maternal satisfaction. In a busy obstetric unit, this may also serve to decrease the anesthetists' workload.     

Fluorescence Microangiography for Quantitative Assessment of Peritubular Capillary Changes after AKI in Mice

AKI predicts the future development of CKD, and one proposed mechanism for this epidemiologic link is loss of peritubular capillaries triggering chronic hypoxia. A precise definition of changes in peritubular perfusion would help test this hypothesis by more accurately correlating these changes with future loss of kidney function. Here, we have adapted and validated a fluorescence microangiography approach for use with mice to visualize, analyze, and quantitate peritubular capillary dynamics after AKI. A novel software-based approach enabled rapid and automated quantitation of capillary number, individual area, and perimeter. After validating perfusion in mice with genetically labeled endothelia, we compared peritubular capillary number and size after moderate AKI, characterized by complete renal recovery, and after severe AKI, characterized by development of interstitial fibrosis and CKD. Eight weeks after severe AKI, we measured a 40%±7.4% reduction in peritubular capillary number (P<0.05) and a 36%±4% decrease in individual capillary cross-sectional area (P<0.001) for a 62%±2.2% reduction in total peritubular perfusion (P<0.01). Whereas total peritubular perfusion and number of capillaries did not change, we detected a significant change of single capillary size following moderate AKI. The loss of peritubular capillary density and caliber at week 8 closely correlated with severity of kidney injury at day 1, suggesting irreparable microvascular damage. These findings emphasize a direct link between severity of acute injury and future loss of peritubular perfusion, demonstrate that reduced capillary caliber is an unappreciated long-term consequence of AKI, and offer a new quantitative imaging tool for understanding how AKI leads to future CKD in mouse models.     

胆胰和胃冲剂对大鼠急性胰腺炎早期小肠粘膜抗氧化损伤的保护

目的：观察大鼠急性胰腺炎早期肠粘膜损伤及胆胰和胃冲剂对小肠粘膜的保护效应及其可能的机制。方法：选择SD大鼠96只，制作急性胰腺炎模型，并设假手术组和胆胰和胃冲剂治疗组，分别于术后2、6、12、24h检测各组动物小肠粘膜的超氧化物歧化酶（SOD）、丙二醛（MDA）和分泌型免疫球蛋白A（sIgA）的含量。结果：急性胰腺炎各组的SOD、MDA、sIgA含量与假手术组各时段相比有明显差异（P＜0．05）；治疗2h组与急性胰腺炎2h组各指标相比无明显差异（P＞0．05）；治疗6、12、24h组与急性胰腺炎组各时段相比有显著差异（P＜0．05）；结论：急性胰腺炎时可引起肠粘膜损伤，胆胰和胃冲剂能增强肠粘膜对氧自由基的清除力，提高肠粘膜的免疫机能。     

Differences in Systemic Opioid Use Do Not Explain Increased Fever Incidence in Parturients Receiving Epidural Analgesia

Background: It has been hypothesized that an increased incidence of fever in patients receiving epidural analgesia might result not from epidural per se, but rather from the antipyretic effect of opioids preferentially administered to women in the no-epidural group. If this were the case, then one would expect the incidence of fever in parturients who did not receive systemic opioids to be independent of whether they received epidural analgesia.

Methods: Using a cohort study design, the authors evaluated the records of 1,233 nulliparous patients whose labor analgesia was managed with (1) no medication (N = 170); (2) 10 mg intravenous systemic nalbuphine plus 10 mg intramuscular every 3 to 4 h as required (N = 327); (3) epidural analgesia with continuous infusion of 0.125% bupivacaine with 2 [mu]g/ml fentanyl (N = 278); or (4) patients who received both systemic nalbuphine and epidural analgesia (N = 458). Fever was diagnosed if the maximum temperature during labor exceeded 100.4[degrees]F (38[degrees]C).

Results: The incidence of fever did not differ according to nalbuphine administration for women not receiving epidural analgesia (1% no nalbuphine, 0.3% with nalbuphine, P = 0.27) or for women receiving epidural analgesia (17% no nalbuphine, 17% with nalbuphine, P = 1.0). However, the incidence of fever differed significantly between patients who received no analgesia as compared to those who received epidural analgesia alone (1%vs. 17%, P = 10-6). Controlling for confounding did not alter these associations.     

The efficacy of thoracic epidural neostigmine infusion after thoracotomy

Few anesthesia studies have explored perioperative continuous epidural infusion of neostigmine. We examined such a regimen in thoracotomy patients. Ninety patients were randomized to one of three groups in this double-blind trial. Before anesthesia induction, an epidural catheter was inserted in all patients at T5-8 levels under local anesthesia. Pre-neo patients received bolus 500-microg epidural neostigmine before anesthesia induction followed by infusion of 125 microg/h until the end of surgery. Post-neo patients received epidural saline during the same time periods plus bolus 500-microg epidural neostigmine at end of surgery. Patients in the control group received saline placebo during all three periods. Patients in the neostigmine groups postoperatively received patient-controlled epidural analgesia with morphine 0.02 mg/mL, bupivacaine 0.08 mg/mL, and neostigmine 7 microg/mL. Control patient-controlled epidural analgesia excluded neostigmine. Data were recorded for 6 postoperative days. Daily patient-controlled epidural analgesia consumption (mL) for Pre-neo patients was significantly less than that of post-neo and control group patients for postoperative days 1-6 (at least 10% and 16% less, respectively; P < 0.05). There was a modest decrease in pain intensity on postoperative days 3-6 for pre-neo patients versus other groups (P < 0.05). These results suggest that continuous thoracic epidural neostigmine started before anesthesia provided preemptive, preventive analgesia and an analgesic-sparing effect that improved postoperative analgesia for these patients without increasing the incidence of adverse effects.     

Epidural analgesia with bupivacaine does not improve splanchnic tissue perfusion after aortic reconstruction surgery

Inadequate splanchnic tissue perfusion is relatively common during and after aortic surgery. We hypothesized that vasodilation caused by thoracic epidural analgesia improves splanchnic blood flow and tissue perfusion after aortic surgery. In this prospective, randomized, controlled study, we studied 20 patients undergoing elective aortic- femoral or aortic-iliac reconstruction surgery. Gastric and sigmoid colon mucosal PCO2 and pH were measured during surgery. An epidural bolus of bupivacaine 40 mg followed by infusion of 15 mg h-1 was started after operation in 10 patients. After operation, splanchnic blood flow and gastric and sigmoid colon mucosal PCO2 and pH were measured before and 2 h after the start of epidural analgesia. During surgery, the gastric mucosal-arterial PCO2 difference remained stable, whereas the sigmoid mucosal-arterial PCO2 difference increased during aortic clamping but returned to pre-clamping values after declamping. After operation, epidural analgesia had no effect on gastric or sigmoid mucosal-arterial PCO2 differences or on splanchnic blood flow.      

急性胰腺炎肠道屏障功能损伤时血浆内毒素和D-乳酸的变化

目的 探讨急性胰腺炎肠道功能损伤时内毒素和D-乳酸的变化.方法 Wistar大鼠随机分为假手术(SO)组和重症急性胰腺炎(SAP)组.术后分4个时段心脏抽血处死,取胰腺组织和回肠组织行组织学检查.偶氮显色法测定血浆内毒素;改良分光光度法测定血浆D-乳酸.结果 SAP组血浆内毒素和D-乳酸随发病时间的延长而持续升高,SO组血浆内毒素和D-乳酸随时间的延长无明显变化.两组比较差异显著(P<0.05).内毒素与D-乳酸呈正相关.(r=0.7323,P<0.05).结论 内毒素和D-乳酸在SAP肠道损伤时升高,可作为评价肠道屏障功能的指标.