Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin.</p><p><b>METHODS</b>Male Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators (t-PA/u-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance.</p><p><b>RESULTS</b>An alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects.</p><p><b>CONCLUSIONS</b>Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.</p>

Population pharmacokinetics of rocuronium delivered by target-controlled infusion in adult patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients.</p><p><b>METHODS</b>Fourteen ASA I-II patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 µg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T₁ scale was blocked by 90% - 95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The population pharmacokinetics analysis was performed using NONMEM program.</p><p><b>RESULTS</b>The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-compartment model. Pharmacokinetic parameters were clearance (CL)₁ = 0.205 L/min, CL₂ = 0.324 L/min, CL₃ = 0.0292 L/min, volumes of distribution (V)₁ = 4.00 L, V₂ = 2.28 L, V₃ = 4.26 L, Vdss = 10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V₁ and CL₁ were negatively correlated with patient age. CL₁ was positively correlated with weight.</p><p><b>CONCLUSIONS</b>No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.</p>

Selection of the early stage differentially expressed genes in rat lung tissue by cDNA microarray after total hepatic ischemia reperfusion injury / 中华外科杂志

<p><b>OBJECTIVE</b>To examine the early changes in gene expression levels in lung tissues by cDNA microarray using a rat model of total hepatic ischemia reperfusion and to analysis function of the changes.</p><p><b>METHODS</b>Twelve adult male SD rats weighting 220 - 250 g were divided randomly into two groups (6 in each group). The rats were sacrificed at end point of the operation and lung tissues were divided into several parts for either microarray analysis or RT-PCR of several genes selected from microarray data. Common change genes were selected from three chips and the final results of microarray analysis were identified by RT-PCR. At last, differentially expressed genes were classified according to their biological functions by cluster analysis.</p><p><b>RESULTS</b>Analysis of the results showed those 48 genes up-regulated and 32 genes down-regulated after hepatic ischemia reperfusion lung injury. Only parts of them had we known about the function. Genes significantly up-regulated were IL-1 alpha, IL-1 beta, SLPI, MMP9, MMP14, MMP15, TIMP1, PIK3RL, MAPK, NF-kappaB, JNK and others. Genes significantly down-regulated were CYP1A1, NQO1, GSTA3, RETNLA and others. Differentially expressed genes were mainly classified into inflammatory reaction, transcription factors, cell metabolism, signals transduction, ion or receptors, cytoskeleton, etc.</p><p><b>CONCLUSIONS</b>cDNA microarray technique provides a new method for detecting differentially expressed genes in rat lung tissues. Further study may reveal the molecular pathologic mechanism of hepatic ischemia reperfusion lung injury and discern new targets for therapeutic interventions.</p>

Effect of nicardipine combined with esmolol on systemic and tissue oxygenation during off-pump coronary artery bypass grafting surgery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The hemodynamics and oxygenation severely fluctuated during the off-pump coronary artery bypass grafting (OPCABG). This study aimed at investigating whether or not nicardipine combined with esmolol (1:10) can maintain systemic and tissue oxygenation during OPCABG.</p><p><b>METHODS</b>Twenty patients scheduled for OPCABG were divided ramdomly into Group nicardipine (N) and Group nitroglycerine (X) respectively combined with esmolol (E) (Dosage ratio: 1 to 10) (Group N + E and Group X + E) with 10 patients in each group. The mixed solution of N + E or X + E were titrated to maintain mean arterial blood pressure between 70 and 80 mmHg following anesthesia induction. The variables of hemodynamics, arterial blood lactate content (Lac) and gastric intramucosal partial pressure of carbon dioxide were measured at the following time points: after induction of anesthesia (T1), pre-revascularization (T2), grafting of left anterior descending (T3), right coronary descending (T4) and left coronary circumflexus branches (T5), post-revascularization (T6), the end of operation (T7). The delivery of oxygen (DO2), consumption of oxygen (VO2) and gastric intramucosal pH (pHi) were calculated.</p><p><b>RESULTS</b>The cardiac index (CI) in Group N + E was significantly increased (P < 0.05) as compared with T1 during OPCABG, while it was mildly decreased in Group X + E. The stroke volumes at T4, T5 in Group N + E and at T3-T6 in Group X + E were significantly decreased (P < 0.05). The systemic vascular resistance indices in Group N + E were significantly decreased as compared with T1 (P < 0.05). The heart rates in these two Groups were significantly elevated intraoperatively (P < 0.05). The DO2 after the infusion of N + E was significantly increased (P < 0.05) or leveled to T1, and the Lac were within the normal range. But the DO2 in Group X + E was decreased throughout the procedure, reaching significant level at T5 (P < 0.05), and the Lac was significantly increased beyond normal range (P < 0.05). The pHi in Group N + E was maintained above 7.35 during OPCABG, while it was less than 7.35 from T4 to T7 in Group X + E.</p><p><b>CONCLUSION</b>Nicardipine combined with esmolol (1:10) regimen may maintain systemic and tissue oxygenation during OPCABG.</p>

Postoperative analgesic and anti-inflammatory effects of rofecoxib after total knee replacement / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the analgesic efficacy and systemic anti-inflammation of preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib, after total knee replacement (TKR).</p><p><b>METHODS</b>Thirty patients underwent elective knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural combined isoflurane anesthesia during surgery and patient-controlled epidural analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine + 0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate postoperative pain intensity. The outcomes included pain scores during rest and movement of knee joints and analgesia satisfaction. Daily morphine consumption was recorded. Circulation leucocyte and serum cytokine concentrations (including interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h after surgery in two groups using RIA. The amount of intraoperative blood loss and postoperative drainage from the knees were measured.</p><p><b>RESULTS</b>The pain scores were significantly less in the group RE than in group E during rest and knee joints movement on the first and second postoperative day, with an improvement in total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = -2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha concentration was significantly lower in group RE than group E at the end of surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after surgery (P < 0.05). There were no significant differences in respect to the amount of intraoperative and postoperative blood loss between two groups (P > 0.05).</p><p><b>CONCLUSION</b>Preoperative cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid requirement and demonstrates a systemic anti-inflammatory effect after TKR.</p>