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Background Limited data are available regarding the perioperative management of cardiac rhythm management devices (CRMDs) exposed to intraoperative electromagnetic interference. We postulated that implementation of a simple, standardized approach to CRMD management using our own institution's Pacing And Cardioverting Electronic Devices peri-Operative Protocol (the PACED-OP protocol) would be associated with a reduction in the amount of device reprogramming without an increase in CRMD-related complications. Methods Records of patients with CRMDs undergoing 497 consecutive surgical procedures were analyzed retrospectively. Roughly half (51%, n = 254) of these procedures occurred before implementation of the PACED-OP protocol, when patients were generally treated according to the American Society of Anesthesiologists' 2005 guidelines. These cases were compared to the remaining surgeries that occurred after implementation of the PACED-OP protocol. Records were screened for evidence of intraoperative CRMD malfunction that was directly associated with the use of electrocautery. Postoperative complications that could be indirectly or possibly linked to electrocautery-mediated CRMD malfunction were also identified. Results Implementation of the PACED-OP protocol was associated with a significant reduction in the odds of device reprogramming (adjusted odds ratio [aOR] 0.19, P

Introduction We have previously defined aspirin resistance detected by TEG PlateletMapping using arachidonic acid (AA). This aspirin resistance is observed as platelet activation (> 20%) by AA in whole blood, even though the isolated platelets are inhibited by aspirin. This platelet activation in whole blood is due to a transcellular pathway mediated by platelets and leukocytes. Methods To determine if this PlateletMapping assay of aspirin resistance on pre-procedure blood samples correlated with an in vivo response we assayed the first voided urine samples collected 2-8 hours post interventional cardiology procedures for 11-dehydro thromboxane B2. Results and Conclusions We detected 27 aspirin resistant patients out of a total of 81 (33%), in agreement with our previous study. All of these patients were on aspirin therapy, confirmed by a

Posttraumatic coagulopathy is a major cause of morbidity. This prospective study evaluated the thrombelastography (TEG) system and PlateletMapping (Haemoscope Corporation, Niles, Ill) values posttrauma, and it correlated those values with transfusions and fatalities. After institutional review board approval, assays were performed on 161 trauma patients. One citrated blood sample was collected onsite (OS), and 1 citrate and 1 heparinized sample were collected within 1 h of arrival to the emergency department (ED). Paired and unpaired t-testing was performed for nominal data with chi square testing for categorical values. Except for a slight increase in clot strength (maximal amplitude (MA)), there were no significant changes from OS to the ED. None of the TEG parameters were significantly different for the 22 patients who required transfusion. PlateletMapping showed lower platelet adenosine diphosphate (ADP) responsiveness in patients who needed transfusions (MA = 22.7 +/- 17.1 vs MA = 35.7 +/- 19.3, P = 0.004) and a correlation of fibrinogen100 mg/dL with fatalities (P = 0.013). For the 14 fatalities, TEG reaction (R) time was 3703 +/- 11,618 versus 270 +/- 393 s (P =0.001), and MA was 46.4 +/- 22.4 versus 64.7 +/- 9.8 mm (P0.001). Hyperfibrinolysis (percent fibrinolysis after 60 min (LY60)15%) was observed in 3 patients in the ED with a 67% fatality rate (P =0.001 by chi-square testing). PlateletMapping assays correlated with the need for blood transfusion. The abnormal TEG System parameters correlated with fatality. These coagulopathies were already evident OS. The TEG assays can assess coagulopathy, platelet dysfunction, and hyperfibrinolysis at an early stage posttrauma and suggest more effective interventions.

Trauma during pregnancy places two lives at risk. Knowledge of risk factors for trauma during pregnancy may improve outcomes.We reviewed the charts of 188 such patients admitted to a Level I trauma center from 1996 to 2004. A comparison was made of injury severity and outcome from a cohort of nonpregnant female trauma patients selected with a similar temporal occurrence and age range.Motor vehicle collisions comprised 160 cases, 67 using a restraint device. Of 84 patients tested, 45 tested positive for intoxicants, 16 positive for 2 or more intoxicants. A significant trend toward less testing through the study period was observed (p = 0.0002). Injury severity was assessed by Revised Trauma Score (RTS). RTS11 or admission to operating room or intensive care units (OR/ICU) classified patients as severely injured. The six maternal fatalities had an RTS11 or OR/ICU disposition. Fetal outcomes included 155 live in utero, 18 live births, and 15 fatalities correlating with injury severity by either criteria (p0.0001). Of the fetal fatalities, 7 occurred with RTS = 12, but only 3 fatalities occurred in the 147 cases not admitted to OR/ICU. Gestational age correlated (p0.0001) with fetal outcomes. The 18 live births had mean gestational ages of 35 +/- 4 weeks as compared with fetal fatalities at 20 +/- 9 weeks, and fetuses alive in utero at 22 +/- 9 weeks gestation. Coagulation tests prothrombin time (PT), international normalized ratio (INR) (both p0.008), and partial thromboplastin time (PTT) (p0.0001) correlated with maternal outcome. A matched cohort of nonpregnancy trauma cases during the same time frame indicated that, despite a significantly higher percentage of severely injured patients, fewer fatalities occurred. This might reflect a greater risk for the pregnant trauma patient.This study of trauma in pregnancy cases revealed a high percentage with risk behaviors. There was a significant trend toward less intoxicant testing in recent years. Coagulation tests were the most predictive of outcomes. Lower gestational age correlated with fetal demise.

The anticoagulant effect of enoxaparin is readily observed by Thrombelastography (TEG), particularly on the reaction time (R) to form a clot, and is completely reversed by heparinase. In this study, recalcified citrated whole blood with heparinase (CNHR) and without (CNR), along with TEG R time, was used to derive a delta R (CNR-CNHR). This delta R (DeltaR) was then used to measure enoxaparin anticoagulation, which was correlated by linear regression (r(2)=0.806) with plasma anti-Xa in 48 thrombophilic pregnancy patients. In a follow up study whole blood from 15 thrombophilic and 15 normal pregnancy subjects was titrated ex vivo with enoxaparin and TEG DeltaR determined. Linear dose responses (all r(2)>0.9) of DeltaR versus plasma enoxaparin concentration were obtained for each subject. A large variation in slope was observed for both thrombophilic (>7 fold, 217 to 1,588 s DeltaR/unit anti-Xa) and normal (>3 fold, 788 to 2,758) pregnancy subjects. The average slope for the thrombophilic group (710 s DeltaR/unit anti-Xa) was significantly (P=0.002) lower than the normal pregnancy group (1,354 s), indicating resistance to enoxaparin anticoagulation in the thrombophilic group. This technique may help gauge the appropriate dose of enoxaparin for each individual, check for residual anticoagulation before invasive procedures, and perhaps help screen for thrombophilic subjects.

Standard activated clotting time (ACT) tests have a poor correlation to bivalirudin levels, leading to uncertainty regarding adequate anticoagulation in percutaneous coronary intervention patients. We tested a Thrombelastograph (TEG) ecarin clotting time (ECT) assay for sensitivity to bivalirudin using blood from 80 patients undergoing interventional cardiology procedures with bivalirudin anticoagulation. This was compared to a standard Hemochron ACT assay using diatomaceous earth. With the TEG assay, the direct thrombin activator, ecarin, was used to initiate coagulation and measured as the reaction time. Plasma samples were evaluated for bivalirudin by a chromogenic assay at an independent hematological laboratory. Linear regression of the standard ACT versus bivalirudin level gave an r = 0.306 whereas the TEG ECT gave a much higher r2 = 0.746 (both P < 0.0001). The TEG ECT should prove more useful than the standard ACT for monitoring bivalirudin anticoagulation across the clinically therapeutic range.

Our recent study determined a difference between preeclamptic and non-preeclamptic patients in platelet potentiation by thrombopoietin (TPO) of reactivity to collagen. The main conclusion was that non-preeclamptic, but not preeclamptic, pregnancy patients' platelets showed significant TPO potentiation at first and third trimesters. Since TPO or B2 Bradykinin platelet receptor levels might influence TPO potentiation, we obtained platelet samples from 187 first trimester pregnant patients prospectively followed through pregnancy. Patients were additionally sampled at third trimester, delivery, and 4 to 6 weeks postpartum. A total of 43 patients, including 11 diagnosed as preeclamptic at third trimester, were sampled at least three different times. We used Western blotting normalized with glyceraldehyde 3 phosphate dehydrogenase as a loading and staining control. There were no significant differences in relative receptor levels between groups or sampling times using repeated measures ANOVA with the mixed model allowing for missing samples. While the mechanism for differences in thrombopoietin potentiation of platelet activation by collagen remains unknown, it may be a first trimester indicator of developing preeclampsia.

Clinically monitoring recovery from clopidogrel and nonsteroidal anti-inflammatory drug (NSAID) inhibition requires whole blood assays corresponding to a standard methodology such as platelet-rich plasma aggregation monitored optically (OPA). We compared OPA, using an ED 50 dose of adenosine diphosphate activation, with 2 whole blood assays, Plateletworks (PWA) and modified Thrombelastograph (TEG). Two sets of assays were performed on 43 surgery patients while on clopidogrel and off clopidogrel to determine the reversal of absolute and relative inhibition. The modified TEG had Spearman correlations with OPA for absolute (rho = .424; P = .006) and relative inhibition (rho = .742; P < .0001). PWA correlations with OPA gave absolute (rho = .28; P = .08) and relative inhibition (rho = .46; P = .004) values. Bland-Altman analysis indicated agreement of both tests with OPA, showing constant biases of about 18% and some dependency on mean magnitude error. Cohen effect size thresholds defined nonresponders as < 7.7% clopidogrel inhibition relative to baseline recovery of full platelet function. Apparent nonresponse to clopidogrel or lack of platelet recovery did not correlate with statin or NSAID therapies. These PWA and modified TEG whole blood assays could prove useful for monitoring the reversal of clopidogrel and NSAID inhibition before surgery. More important, these assays done at baseline and after beginning clopidogrel therapy could monitor the effectiveness for the individual patients with cardiovascular disease and help identify the need for alternative therapies.

To determine whether a difference exists in platelet reactivity to collagen and potentiation by thrombopoietin (TPO) between preeclamptic and non-preeclamptic patients, 187 first trimester pregnant patients were prospectively followed through pregnancy. Citrated blood, drawn at first (14 weeks estimated gestational age) and third trimesters (28 weeks), when patients were admitted for delivery, and 4-6 weeks postpartum, was assayed by a Whole Blood Impedance Aggregometer measuring platelet activation by 0.4 mug/ml collagen, +/-10 ng/ml TPO. There was no significant difference in 1st trimester platelet collagen activation by unpaired t-test between groups. Significant TPO potentiation of collagen activation (P0.05, paired t-test) was observed in non-preeclamptic patients at the first and third trimesters. In contrast, preeclamptic patients' platelets show no significant (P0.8, paired t-test) TPO potentiation at any time. While the mechanism for this difference in thrombopoietin potentiation of platelet activation by collagen as early as the first trimester is unknown, it may be one of the initiating events in this syndrome.

Platelet function was evaluated before and after clopidogrel therapy in 50 cardiology candidates scheduled for intervention; results were averaged from optical platelet aggregation with 2 significantly correlated point-of-care instruments, Thrombelastograph and Ichor PlateletWorks. Although this was a limited study with few complications, the failure of clopidogrel therapy (30% nonresponders with

BACKGROUND Aspirin-resistant platelet activation in whole blood is attributable to a transcellular pathway not detected by isolated platelet aggregometry. Aspirin resistance as defined by urinary thromboxane levels is associated with increased risk for myocardial infarction or cardiac death. Whole blood point-of-care assays may also detect aspirin resistance. METHODS We compared PlateletMapping® with VerifyNow® for detecting aspirin resistance in 200 patients undergoing invasive cardiac procedures. This included 10 patients not receiving aspirin therapy for comparison. The assay results were correlated with urinary 11-dehydro-thromboxane B2 collected 2 to 8 hours after the procedure. RESULTS PlateletMapping detected aspirin resistance in 32% of patients. VerifyNow detected aspirin resistance in 6% of patients. A patient's compliance with aspirin therapy was confirmed by a

Limited data are available regarding the perioperative management of cardiac rhythm management devices (CRMDs) exposed to intraoperative electromagnetic interference. We postulated that implementation of a simple, standardized approach to CRMD management using our own institution's Pacing And Cardioverting Electronic Devices peri-Operative Protocol (the PACED-OP protocol) would be associated with a reduction in the amount of device reprogramming without an increase in CRMD-related complications.Records of patients with CRMDs undergoing 497 consecutive surgical procedures were analyzed retrospectively. Roughly half (51%, n = 254) of these procedures occurred before implementation of the PACED-OP protocol, when patients were generally treated according to the American Society of Anesthesiologists' 2005 guidelines. These cases were compared to the remaining surgeries that occurred after implementation of the PACED-OP protocol. Records were screened for evidence of intraoperative CRMD malfunction that was directly associated with the use of electrocautery. Postoperative complications that could be indirectly or possibly linked to electrocautery-mediated CRMD malfunction were also identified.Implementation of the PACED-OP protocol was associated with a significant reduction in the odds of device reprogramming (adjusted odds ratio [aOR] 0.19, P0.001). There was no direct evidence of CRMD malfunction in either cohort. The rate of postoperative complications that could be indirectly or possibly linked with electrocautery-mediated CRMD damage did not differ significantly between cohorts (aOR = 1.37, 95% confidence interval 0.56-3.3, P = 0.49).The PACED-OP protocol implementation was associated with a significant reduction in the odds of device reprogramming without a significant difference in the odds of CRMD-related complications.

Study Objective To validate a Thromboelastograph (Haemoscope Corporation, Niles, IL) assay for functional fibrinogen. Design Correlation study of the Thromboelastograph assay with two conventional fibrinogen assays by the standard Clauss method. Setting Research laboratory of a university medical center. Participants and Interventions Blood samples were obtained from 19 healthy volunteers. Measurement and Main Results Thromboelastograph assays, using heparinized whole blood from 19 healthy donors, indicated that reptilase-XIIIa mixture (Activator f )–generated clot shear elasticity in dynes per square centimeter ( G f ) correlated with fibrinogen (mg/dL). Blood from four donors was used to define the contribution of hematocrit (Hct) to G f by titration with platelet-rich plasma. The G f versus Hct gave linear correlations ( r 2 = 0.746) with G f = 1258 − 17.8 × % Hct. A commercial collection of 19 normal, 10 borderline, and one deficient for functional fibrinogen-citrated plasmas was assayed for G f after recalcification using Activator f . Of the 30 plasma samples, four were from factor X– or factor VII–deficient donors and one was from a coumadin-treated donor. There was a linear correlation of Activator f G f with functional fibrinogen ( r 2 = 0.940) with G f = −730 + 9.21 × fibrinogen (mg/dL). Conclusion Thrombelastography with Activator f may be used to determine fibrinogen levels in whole blood.

The authors evaluated the correlation of post-cardiopulmonary bypass surgery bleeding, measured as 24-hour chest tube output/kilogram body weight, with platelet function tests using glass bead adhesion and Thrombelastograph Platelet Mapping (Haemoscope Corporation, Niles, Ill); coagulation tests; patient characteristics; surgery parameters; and visual assessment of surgical field bleeding before closure as not bleeding (code 1), oozing (code 2), and excessive bleeding (code 3). All platelet function and coagulation tests indicated significant dysfunction 15 minutes after protamine neutralization of heparin. With the exception of glass bead adherence, these assays indicated poor recovery of function 1 hour postoperatively. By multiple regression, the most significant predictors of postoperative bleeding were a low body mass index (BMI) (P < 0.0001), lowest core body temperature (P = 0.0006), and cross clamp time (P < 0.0001). Low core temperature was significantly (P < 0.0001) correlated with cross clamp time, which the authors believe is the most likely cause of coagulation and platelet dysfunction. None of the platelet function tests significantly correlated with bleeding. Looking at the highest quartile of chest tube output patients (n = 19) versus the upper and lower 50th percentile of coagulation and platelet function, bleeding could be explained for 11 patients by BMI plus surgery parameters along with coagulation and/or platelet dysfunction. In three cases without negative surgery parameters, coagulation dysfunction was observed. The remaining five cases did not give a clear indication of which parameters were primarily responsible for the bleeding.

Optical platelet aggregation (OPA) with platelet-rich plasma (PRP) was compared with a Thrombelastograph (TEG) whole blood assay for monitoring arachidonic acid (AA)-induced platelet activation. Assays were performed on 47 interventional cardiology and 24 general surgery patients receiving aspirin therapy for cardiovascular disease, as well as 48 volunteers asked to take nonsteroidal anti-inflammatory drugs (NSAIDs) or 12 volunteers on chronic NSAID therapy unrelated to diagnosed cardiovascular disease. Whole blood TEG monitoring of NSAID inhibition detected NSAID-insensitive AA activation of platelets in a significantly higher number of cardiology (23%) and surgery (25%) patients and normal volunteers on chronic NSAID (25%) therapy relative to normal subjects not on chronic NSAID therapy (0%). Whole blood NSAID insensitivity was observed with cyclooxygenase-I inhibitors, such as aspirin and ibuprofen; was not affected by Celebrex, a cyclooxygenase-II inhibitor; but was completely inhibited by thromboxane-receptor antagonists. This was not due to platelet NSAID insensitivity, because complete inhibition of AA-activation responses in PRP was observed with either TEG or OPA assays. We confirmed that thromboxane B(2) formation in PRP from NSAID-insensitive subjects was completely inhibited by NSAIDs. However, significant amounts were formed in whole blood from NSAID-insensitive subjects, but not in whole blood from NSAID-sensitive subjects. Thromboxane formation after AA addition was not found in washed blood cells with 90% reduced platelet counts or in leukocyte-rich buffy coat fractions, but could be restored by addition of PRP. NSAID-insensitive activation was inhibited by nordihydroguaiaretic acid, with an IC(50) of 30 micromol, implicating 12- and/or 15-lipoxygenases in this transcellular pathway.

We used a thrombelastograph (TEG) assay with tissue factor and kaolin (TEG TF/K) to measure activated clotting time (ACT) in 31 patients during cardiopulmonary bypass. For comparison, ACTs were also determined by a Hemochron Jr. Signature and a Hepcon HMS. The TEG TF/K correlated with both the Hepcon (r(2) = 0.789) and Hemochron (r(2) = 0.743) ACTs. The average ACT after heparin was 319 +/- 119 s (mean +/- sd) for the TEG TF/K compared with 624 +/- 118 s for the Hepcon instrument. To evaluate the effects of hemodilution on TEG TF/K and Hemochron assays, ACT assays were performed on blood diluted to 50% and titrated with heparin from 0 to 6 U/mL. Both instruments showed significant (P0.01) changes in the ACT-versus-heparin slope, but the 0 heparin intercept for the TEG TF/K ACTs was not significantly changed (P = 0.292), in contrast to that for the Hemochron device (P = 0.041). Both instruments also indicated the same 1.3:1 ratio of protamine to heparin for optimum heparin neutralization, with increasing ACTs at ratios2.6:1. The TEG TF/K ACT assay rapidly monitors heparin anticoagulation, in addition to the capabilities of this instrument to monitor platelet function, clotting factors, and fibrinolysis.

The aim of this study was to describe the clinical, functional, and morphologic characteristics of platelets in Cavalier King Charles Spaniel dogs (Cavaliers).Blood from 69 clinically normal Cavaliers was collected and anticoagulated with ethylenediamine-tetraacetic acid (EDTA) and citrate. Automated and manual platelet counts were obtained. Percent platelet aggregation in response to ADP (2, 4, 8, 16, and 32 microM) was determined. Electron microscopy was performed to examine platelet internal morphology and dense granule distribution. A cardiologist recorded the quality of murmurs.Thrombocytopenia (100,000/microL) was present in 51.43% (36/69) of Cavaliers. Macrothrombocytes (3 microm) were present in 33.33% (22/69). Mean manual platelet count was 118,770/microL. Manual (EDTA blood) and automated (EDTA and citrated blood) methods of platelet counting were correlated. Prevalence of cardiac murmurs was 38% (26/69). There was no association between affected dogs and murmur, signalment, or coat color. Mean percent platelet aggregation was significantly higher in controls than in Cavaliers (79% vs 38%, p=0.001). Response to ADP was unaffected by thrombocytopenia, macrothrombocytes, murmur, or any combination thereof. Platelet electron microscopy showed normal and giant sized platelets with normal internal morphology.A benign inherited giant platelet disorder affects approximately 50% of Cavalier King Charles Spaniels. It is characterized by thrombocytopenia, macrothrombocytes, or decreased platelet aggregation in response to ADP. Platelet ultrastructure is normal. Citrated or EDTA blood provides accurate platelet counts. Further studies are indicated to determine platelet glycoprotein structure and any association with mitral endocardiosis. Cavaliers may be useful models of inherited giant platelet disorders.

Study objective To evaluate a point-of-care (POC) coagulation monitoring analyzer (CoaguChek™ Pro DM) in patients undergoing cardiopulmonary bypass (CPB). Design Prospective, blinded study. Setting University hospital. Participants 32 patients scheduled for elective cardiac surgery with CPB. Intervention Arterial blood samples were drawn four times: preoperatively, postinduction, and 10 minutes and 60 minutes after reversal of heparin with protamine. Measurements and main results Activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured with a point-of-care system—CoaguChek™ Pro DM as well as with the Core Laboratory facility using a MD180 analyzer. A total of 128 consecutive paired analyses were conducted. There was very good agreement of the point-of-care-based monitoring of aPTT and PT with the Core Laboratory-based monitoring of aPTT and PT (positive correlations by linear regression analysis: r 2 = 0.83 and 0.92, respectively). The turn-around time (time from blood sampling until availability of data for the anesthesiologists) was significantly shorter for the point-of-care system (averaging 30 min). Conclusion CoaguChek™ Pro DM is a reliable and time-efficient point-of-care system for monitoring coagulation of patients undergoing CPB. The use of this system may improve patient care in this group through timely and accurate clinical decisions.

Objective: Proinflammatory eicosanoids and cytokines are important mediators of local inflammation in acute lung injury. We determined if enteral nutrition with anti-inflammatory fatty acids, eicosapentaenoic acid, and γ-linolenic acid would reduce the intrapulmonary synthesis of proinflammatory eicosanoids and cytokines and pulmonary neutrophil accumulation in a rat model of acute lung injury. Design: Prospective, randomized, controlled, double-blind study. Setting: Research laboratory at a university medical center. Subjects: Male Long-Evans rats (250 g). Interventions: Rats were randomly assigned to three dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/ day) containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, or 20% fish and 20% borage oil for 21 days. On day 22, bronchoalveolar lavage was performed 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/ kg) or saline. Bronchoalveolar lavage fluid was analyzed for leukotriene B 4 , leukotriene C 4 /D 4 , thromboxane B 2 , prostaglandin E 2 , 6 keto-prostaglandin F 1α , tumor necrosis factor (TNF)-α, and macrophage inflammatory protein-2 (MIP-2). Lung myeloperoxidase activity (a marker for neutrophil accumulation) and phospholipid fatty acid composition were also determined. Measurements and Main Results: Lung phospholipid concentrations of arachidonic acid were lower and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher with fish oil and fish and borage oil as compared with corn oil. Dihomo-γ-linolenic acid, the desaturated and elongated intermediate of γ-linolenic acid, increased with fish and borage oil as compared with fish oil and corn oil. The levels of leukotriene B 4 , leukotriene C 4 /D 4 , 6-keto-prostaglandin F 1α and thromboxane B 2 with corn oil were significantly increased with endotoxin as compared with saline. In contrast to the corn oil group, endotoxin did not significantly increase bronchoalveolar lavage levels of leukotriene B 4 , leukotriene C 4 /D 4 , and thromboxane B 2 above those of saline-treated rats with fish oil and fish and borage oil. Lung myeloperoxidase activity was significantly increased in endotoxin-treated rats compared with those rats given saline in all dietary treatment groups. However, lung myeloperoxidase activity was significantly lower with either fish oil or fish and borage oil as compared with corn oil after endotoxin. Although endotoxin increased the levels of TNF-α and MIP-2 with all dietary treatment groups as compared with saline-treated rats, there were no significant differences in the levels of either cytokine between the dietary treatment groups. Conclusions: These results indicate that dietary fish oil and fish and borage oil as compared with corn oil may ameliorate endotoxin-induced acute lung injury by suppressing the levels of proinflammatory eicosanoids (but not TNF-α or MIP-2) in bronchoalveolar lavage fluid and reducing pulmonary neutrophil accumulation.

Objectives: Proinflammatory eicosanoids (cyclooxygenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and γ-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n-6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition. Design: Prospective, randomized, controlled, double-blind study. Setting: Research laboratory at a university medical center. Subjects: Male Long-Evans rats, weighing 250 g. Interventions: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B 4 and B 5, thromboxane A 2 , prostaglandin E 2 , and 6keto-prostaglandin F 1α were measured in a third group of prefed rats. Measurements and Main Results: Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p =.06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B 4 , prostaglandin E 2 , and thromboxane B 2 released from A23187-stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p =.20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher, with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-γ-linolenic acid, the desaturated and elongated intermediate of γ-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil. Conclusions: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B 4 , thromboxane B 2 , and prostaglandin E 2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids. The modulation of proinflammatory eicosanoid synthesis with anti-inflammatory fatty acids, eicosapentaenoic acid, and docosapentaenoic acid and γ-linolenic acid, may have reduced the seve

Objective: To determine if cytokine responses and lung injury induced by intravenous (iv) lipopolysaccharide (LPS) at 4 hr were enhanced in rats that had been previously subjected to 30 min of total liver ischemia (Pringle's maneuver) followed by 24 hr or 3 days of reperfusion. Background: Many patients with liver trauma require occlusion of hepatic blood flow to control hemorrhage and facilitate repair. A significant number of these patients subsequently develop the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MOD) characterized by the release of cytokines and tissue neutrophil influx. Macrophages, including Kupffer cells, may be activated by ischemic injury and dysregulation of their response to LPS may contribute to the development of SIRS and acute respiratory distress syndrome. Methods: Adult male Sprague–Dawley rats were randomly divided into six groups: three groups received total hepatic ischemia for 30 min and three groups had a sham procedure. Twenty-four hours or 3 days after hepatic ischemia/reperfusion injury, rats were treated with LPS (5 mg/kg) or saline and monitored for 4 hr. We collected serum, bronchoalveolar lavage (BAL) fluid, and lung tissue. Results: Serum and BAL cytokine concentrations were significantly increased by iv LPS; however, hepatic ischemia/reperfusion injury 24 hr or 3 days before iv LPS ameliorated this cytokine response. The LPS-induced pulmonary neutrophil influx and histopathological changes were similar in sham and hepatic ischemia/reperfusion-injured groups. Conclusions: Hepatic ischemia/reperfusion injury significantly attenuated the serum and BAL cytokine concentrations, but did not change pulmonary neutrophil influx or histopathological alterations in response to iv LPS.

Gynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain. This study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone™) or an optically identical placebo injection of Intralipid™ and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined. Although the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056) in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative period. Intraoperative ketorolac treatment significantly lowered (P = 0.027) pain scores and reduced the postoperative requirement for additional pain relief drugs. There was a lack of efficacy of preoperative sustained release betamethasone in reducing postoperative pain despite maintaining a therapeutic concentration during the postoperative period. Intraoperative Ketorolac did afford some short-term pain relief in the postoperative period and reduced the need for additional pain relief drugs.