[Clinicopathological features and prognosis of colorectal stromal tumor].

OBJECTIVE: The incidence of colorectal stromal tumor is low among digestive tract tumors, therefore the literatures about clinicopathological features and prognosis of colorectal stromal tumor are few at home and abroad. In this study, we performed survival analyses for colorectal stromal tumor. The nomogram made by prognostic factors provided basis for evaluation of prognosis. METHODS: The clinico-pathological and prognostic data of colorectal stromal tumor between January 1992 and December 2015 were collected from the surveillance, epidemiology, and end results (SEER) database. The survival analyses were made by SPSS 24.0 software. The nomogram and calibration curve were made by RMS package in R 3.5.2 software. RESULTS: In the study, 546 patients with colorectal stromal tumor were included. The median age of onset was 64 years. The regional lymph node metastasis (LNM) rate was 9.4%. The multivariate Cox regression analyses of the 546 cases showed that the older age of onset (>64 years), single or divorce, colon tumor (compared with rectal tumor), non-surgery, high histological grade, LNM and distant metastasis were associated with worse cancer specific survival (CSS) and overall survival (OS), P < 0.05 for all. The treatment district was independent prognostic factor of OS (P = 0.027). The C-index of independent prognostic factors predicting CSS and OS probability were 0.76 (95%CI: 0.72-0.80) and 0.75 (95%CI: 0.72-0.78), respectively. Multivariate analyses were further carried out in the 174 patients with definite histological grade and tumor location, which revealed that the age of onset, histological grade, surgery or not were independent prognostic factors of CSS and OS (P < 0.05 for all). Tumor location was associated with CSS (P = 0.041) but not OS (P = 0.057) among the 174 cases. Four independent prognostic factors influencing the 174 patients' prognosis were used to make nomogram for predicting survival probability of 546 cases. The C-index of four prognostic factors predicting probability of CSS and OS of the 546 cases were separately 0.71 (95%CI: 0.66-0.75) and 0.73 (95%CI: 0.70-0.77). The nomogram had more accuracy for predicting OS probability of colorectal stromal tumors. CONCLUSION: The prognosis of colorectal stromal tumor was affected by multiple clinicopathological factors. The nomogram provided the basis for predicting the survival probability of patients with colorectal stromal tumor.

MiRNA-188-5p alleviates the progression of osteosarcoma via target degrading CCNT2.

OBJECTIVE: The aim of this study was to investigate the biological role of microRNA-188-5p (miRNA-188-5p) in mediating the progression of osteosarcoma by degrading CCNT2. PATIENTS AND METHODS: The relative expression levels of miRNA-188-5p and CCNT2 in osteosarcoma tissues and para-cancerous normal tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, their expression levels in osteosarcoma cell lines were examined. The regulatory effects of miRNA-188-5p on the proliferative ability and cell cycle progression of osteosarcoma cells were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Dual-Luciferase reporter gene assay was applied to verify the binding relationship between miRNA-188-5p and CCNT2. Furthermore, rescue experiments were conducted to clarify the role of miRNA-188-5p/CCNT2 in mediating the progression of osteosarcoma. RESULTS: MiRNA-188-5p was lowly expressed in osteosarcoma tissues when compared with paracancerous normal tissues. Overexpression of miRNA-188-5p significantly suppressed the proliferative ability and arrested cell cycle progression of osteosarcoma cells. However, knockdown of miRNA-188-5p obtained the opposite trends. The Dual-Luciferase reporter gene assay verified the binding relationship between miRNA-188-5p and CCNT2. The expression level of CCNT2 in HOS and MG-63 cells was markedly downregulated after transfection of miRNA-188-5p mimics. In addition, overexpression of CCNT2 could partially reverse the inhibitory effect of miRNA-188-5p on the proliferative ability and cell cycle progression of osteosarcoma cells. CONCLUSIONS: MiRNA-188-5p is downregulated in osteosarcoma. Furthermore, it suppresses the proliferative ability and cell cycle progression of osteosarcoma cells via target degrading CCNT2.

microRNA-1205 promotes cell growth by targeting APC2 in lung adenocarcinoma.

OBJECTIVE: An increasing amount of evidence indicates that microRNAs (miRNAs) can be potential diagnostic and prognostic markers for various cancers. In this study, a novel miRNA, miR-1205, was identified in lung adenocarcinoma (LUAD). PATIENTS AND METHODS: First, the expression of miR-1205 in tissues was determined and verified to be correlated with the prognosis of patients. Overexpression and knockdown in LUAD cells were chosen to evaluate the effect of miR-1205 on cell growth in vitro. Luciferase assays, Western blot and rescue assays were performed to screen and confirm potential targets of miR-1205. RESULTS: We demonstrated that miR-1205 was down-regulated in the tissues of LUAD, and that miR-1205 may be a predictor of overall survival of LUAD. The overexpression of miR-1205 promoted cell proliferation and colony formation. Our results indicated that miR-1205 targeted APC2 directly, serving as a vital part in accelerating LUAD cell proliferation. CONCLUSIONS: We showed that miR-1205 could promote LUAD cell growth by targeting APC2 protein expression and provided further proof of miR-1205 as a potential non-invasive biomarker and therapeutic target for LUAD.

[Analysis of characteristics and influence factors of diagnostic delay of endometriosis].

Objective: To access the influence factors of diagnostic delay of endometriosis. Methods: We designed a questionnaire of diagnostic delay of endometriosis. From February 2014 to February 2016, 400 patients who had dysmenorrhea and diagnosed with endometriosis by surgery in Peking University Third Hospital were surveyed retrospectively. Time and risk factors of diagnostic delay were analyzed. Results: The diagnostic delay of 400 patients was 13.0 years (0.2-43.0 years), 78.5%(314/400) patients thought pain was a normal phenomenon and didn't see the doctor. Patients who suffered dysmenorrhea at menarche experienced longer diagnostic delay than those who had dysmenorrhea after menarche (18.0 vs 4.5 years; Z=191.800, P<0.01) . Patients who suffered aggravating dysmenorrhea experienced shorter delay time than those who suffered stable or relieving dysmenorrhea (11.0 vs 12.5 vs 18.0 years; Z=8.270, P<0.05) , with the difference statistically significant, single factor analysis shows. Severe dysmenorrhea, deep infiltration endometriosis (DIE) , family history of dysmenorrhea or endometriosis, previous surgical history of endometriosis, high stage, with infertility, adenomyoma or other symptoms, could help to shorten diagnostic delay with no significant difference (P>0.05) . By multiple logistic regression analysis, the results shown that whether have dysmenorrhea at menarche and clinical diagnosis time were the independent factors affecting delayed diagnosis (P<0.01) . Conclusions: Diagnostic delay of endometriosis is common and the mean delay time is 13.0 years mainly due to the unawareness of dysmenorrhea. Dysmenorrhea at menarche, clinical diagnosis time and dysmenorrhea intensity are the factors affecting time of diagnostic delay.

Photosensitizer-induced self-assembly of antigens as nanovaccines for cancer immunotherapy.

Herein, the photosensitizer indocyanine green (ICG) is used to induce the self-assembly of antigens to form nanovaccines. Under near-infrared (NIR) laser irradiation, reactive oxygen species can be generated by nanovaccines to disrupt the membranes of endo/lysosomes, which helps to release antigens into the cytosol efficiently, thereby enhancing antigen cross-presentation and anti-cancer immunity. To the best of our knowledge, this study represents the first example of ICG as a biocompatible adjuvant to improve cancer vaccine efficacy.

[Role of oral contraceptives in preventing endometriosis-related pain progression].

Objective: To analyze the effect of oral contraceptives on dysmenorrhea in patients with endometriosis. Methods: We designed dysmenorrhea and chronic pelvic pain questionnaire.From February 2014 to February 2016 in the Gynecological Department of Peking University Third Hospital, patients suffered dysmenorrhea with or without endometriosis or adenomyosis were included.According to their own willingness, patients were divided into the research group and the control group.The research group periodically took oral contraceptives (Diane-35 or Yasmin), while the control group received no treatment.They were followed-up about dysmenorrhea every six months, and the total follow-up time was one and a half year. Results: The dysmenorrhea VAS scores of patients in research group after taking oral contraceptives for six or twelve months were significantly lower than that in baseline (VAS 4 vs 5 vs 7). The dysmenorrhea VAS scores increased after quitting medication, but remained still lower than baseline (VAS 6.5 vs 7). However, the dysmenorrhea VAS scores of patients in control group remained unchanged (VAS 6 vs 6). Patients who took pills for more than one year experienced the same severity of dysmenorrhea after six months' or one year's medication (VAS 2 vs 2), and they suffered slowly aggravating recurrent dysmenorrhea, while those who quitted after six months' medication suffered quickly recurrent dysmenorrhea.The relieving rate of dysmenorrhea in research group was significantly higher than that in control group (79.7% vs 8.2%), and the relieving rate in patients with severe pain was significantly higher than that with mild or moderate pain (87.0% vs 66.6 % vs 77.1%). The relieving rate in patients without lesions was significantly higher than patients with adenomyosis (92.6% vs 59.1%). Conclusions: Endometriosis is a progressing disease. Longterm medication of oral contraceptives can relieve the dysmenorrhea pain.The extent of pain relief was not connected with the length of medication.Dysmenorrhea recurred after quitting medication, and the longer of medication, the slower pain recurred.Patients without lesions experienced higher pain relieving rate than those with adenomyosis.

[The expression of serum endoplasmic reticulum stress protein-78 in obstructive sleep apnea patients].

OBJECTIVE: This study aimed to detect serum level of glucose regulated protein 78(GRP78) in patients with obstructive sleep apnea(OSA) and explore the relationship between endoplasmic reticulum stress and the pathophysiology of OSA. METHODS: A total of 91 patients with OSA were enrolled in this study, including 30 mild, 28 moderate and 33 severe. The other 27 obese subjects were of age, gender and BMI matched group. Eleven moderate or severe OSA patients were administrated with continuous positive airway pressure (CPAP) treatment for 24 hours. Polysomnography, apnea hypopnea index (AHI), lowest arterial oxygen saturation(SaO2) and percentage of time spent at SaO2 below 90% (SIT90) were measured before and after sleep. Serum GRP78 was measured by ELISA. RESULTS: The expression of GRP78 in mild(3.42±0.97)µg/L, moderate(2.67±1.14)µg/L and severe(2.62±1.11)µg/L OSA groups was significantly higher than in control group(1.75±0.41)µg/L (P<0.05). The GRP78 level in mild OSA group was significantly higher than either moderate or severe OSA group (P<0.05). After 24 h treatment of CPAP, serum GRP78 level decreased significantly [(1.77±0.39)µg/L vs(2.84±0.39)µg/L; P<0.05]. CONCLUSIONS: Endoplasmic reticulum stress involves in the pathophysiology of patients with OSA. Higher GRP78 level in mild OSA patients suggests that endoplasmic reticulum related protein GRP 78 might rise then fall during exacerbation of OSA.

Beneficial effects of jejunal continuity and duodenal food passage after total gastrectomy: a retrospective study of 704 patients.

AIM: To evaluate effects of reconstruction procedures on post-operative outcomes and nutritional status after total gastrectomy. METHODS: The study group comprised 704 consecutive patients with gastric cancer who underwent total gastrectomy between December 1985 and December 2003. Six alimentary reconstruction procedures were performed, including jejunal continuity [Braun, modified Braun I and II and functional jejunal interposition (FJI)] and jejunum transection ["P" Roux-en-Y and "P" jejunal interposition (PJI)]. The duodenal food passage was maintained only by FJI and PJI. We evaluated the time interval to restore food intake after surgery and the incidence of complications and nutritional status for 12 months. RESULTS: Patients who received jejunum transection required 7.8+/-2.5 days and 11.9+/-4.9 days to restore liquid and semi-liquid food intake, respectively, which reduced to 3.9+/-2.1 days for liquid and 7.9+/-3.9 days for semi-liquid food intake by jejunum continuity. The incidence rates of reflux esophagitis and Roux-en-Y syndrome in patients receiving jejunum transection were 23.5% and 42.4%, respectively, which were decreased to 9.35% and 14.7%, respectively, by jejunal continuity. Furthermore, prognostic nutrition index score of patients receiving the procedures maintaining duodenal food passage (52.9+/-10.9) was higher than that of patients without the duodenal food passage (46.7+/-8.2). CONCLUSION: Jejunal continuity and duodenal food passage showed beneficial effects on clinical outcomes after surgery. Among these six procedures, FJI was the only procedure to combine the benefits of jejunal continuity and maintaining the duodenal food passage, indicating that FJI has potential clinical application to improve the quality of patient's life after total gastrectomy.

[Adsorption of TNF alpha onto the amino acid-modified NK-110 resin].

It is a effective way to remove Tumor Necrosis Factor(TNF alpha) from plasma by adsorbent. In the present study, NK-110 was modified by 8 amino acids to prepare the adsorbents to be used in the static adsorption experiments of TNF alpha. We have studied the adsorption capacity, kinetic profiles and adsorption isoterm of Cys modified NK-110, and some comparison were made between Cys modified NK-110 and unmodified one. The experimental results show that the Cys modified NK-110 exhibited superior adsorption capacity which is 7683.80 u/mL, and the adsorption percentage is 85.38% at 120 min in stable adsorption. Compared with unmodified NK-110, the Cys-modified one with high adsorption velocity. Furthermore, adsorption isotherms were also studied on Cys-modified and bare NK-110, bot showed to be of "L" shape at 37 degrees C. The adsorption amount increased as the concentration of TNF alpha increased, however, the adsorption percentage is stable adsorbed by Cys-modified NK-110, whereas it is decreased by bare one. The results demonstrating that Cys can significantly raised the adsorption capacity.

Development of a DNA immunoadsorbent: coupling DNA on sepharose 4FF by an efficient activation method.

To remove anti-DNA antibodies from a patient's plasma with systemic lupus erythematosus (SLE), a DNA immunoadsorbent was developed by covalently coupling calf thymus DNA on activated Sepharose 4FF. Sepharose 4FF was activated with 5-norbornene-2,3-dicarboximido carbonochloridate (Cl-CO-ONB), which was proven to be a very effective method for preparation of affinity chromatographic adsorbents. The activation was carried out in dry acetone using 4-(dimethylamine)pyridine (DMAP) and triethylamine (TEA) as catalysts at 4 degrees C or at room temperature. The coupling of DNA to the activated support was investigated as a function of pH, temperature, time, concentration of DNA, and activation level. It was found that the pH for optimal coupling is 3.0, and the amount of coupled DNA increases with an increase either in the concentration of DNA or the activation level. The maximum amount of coupled DNA could reach 1.0 mg DNA/ml support. The incubation of 5 to 20 ml of SLE plasma with 1.0 ml of adsorbent resulted in an 80 to 90% decline in the anti-DNA antibody level. Nonspecific adsorption for normal IgG and total protein is less than 15%.

Effect of selective inhibition of cyclooxygenase 2 on temporary focal cerebral ischemia in rats.

Cyclooxygenase 2 (COX2) is the inducible isoform of COX but its involvement in ischemic neuronal injury is unclear. The effect of selective inhibition of COX2 was evaluated by intraperitoneal administration of NS-398, a selective COX2 inhibitor, before and after 2 h of temporary focal ischemia in rats. After 4 h of reperfusion, the infarct volume and the hemispheric concentration of prostaglandin E2 (PGE2), a major substance produced by COX2, were assessed. The infarct volume was unchanged by NS-398 administration. There was no difference in PGE2 levels between the ischemic and the contralateral hemispheres in the control group. However, PGE2 concentration significantly decreased in the ischemic hemisphere in the NS-398 group. The results are consistent with the previous observation that COX2 is induced in peri-ischemic areas and suggests that COX2 has a significant role in peri-ischemic pathophysiology.

Clinical trials of type I and in vitro studies of type II immunoadsorbents for systemic lupus erythematosus therapy.

A highly selective immunoadsorbent was prepared by immobilization of DNA on carbonized resin beads (Type I) for the removal of the pathogenic antibodies of systemic lupus erythematosus (SLE) patients. Thirty cases of clinical trials of this SLE therapy were performed at 12 hospitals in China. The levels of anti-DNA antibodies after whole blood perfusion were decreased 40-70%. Almost all the symptoms were relieved, and some patients were freed from medicine administration. A new immunoadsorbent was prepared using aminated cellulose beads (Type II) having a higher DNA immobilization capacity of 0.6 mg/ml than the 0.4 mg/ml capacity for Type I. Stationary adsorption tests with the sera of SLE patients showed that the Type II immunoadsorbent could remove 60% of the pathogenic antibodies, which is much higher than the 30% for the Type I adsorbent.

Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2.

BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock.

Transpulmonary prostaglandin F2 alpha metabolism in sheep: an in vivo model.

We investigated transpulmonary enzymatic conversion of prostaglandin F2 alpha (PGF) to the 13,14-dihydro-15-keto metabolite (PGFM) in normal and acutely lung injured sheep. PGF was infused directly into the right ventricle. Sequential, simultaneous blood samples were drawn from the pulmonary artery (PA) and aorta (A). PGF and PGFM plasma concentrations were quantitated by double antibody radioimmunoassay (RIA). The pulmonary conversion rate of PGF in normal lung was established over a wide range of concentrations in intubated, normoxic, and hemodynamically stable sheep. Both zero and first order kinetics were present. PGF had no physiological effects on either pulmonary or systemic hemodynamics at any infusion rate studied. Acute lung injury was produced by intravenous injections of oleic acid into the PA until the resting mean pulmonary artery pressure doubled. Infusions were then repeated and fractional metabolism of PGF across the lung was assessed. PGF, at infusion rates of 2 micrograms/kg/min and 8 micrograms/kg/min, was metabolized greater than 70% respectively. Thus, there was no difference between control or experimental groups in PGF conversion. We conclude that the in vivo sheep lung has an extensive substrate-dependent capacity to metabolize PGF and this mechanism is resistant to severe acute oleic acid lung injury.

High tidal volume ventilation produces increased lung water in oleic acid-injured rabbit lungs.

Repeated lung inflation with very high tidal volumes (VT) is associated with the production of permeability pulmonary edema in animal models using previously normal lungs. We studied the effect of mechanical ventilation, at VT values approaching those used clinically, on lung weight gain (lung water) in salt-perfused rabbit lungs diffusely injured by the administration of oleic acid. Lungs ventilated at a VT of 18 ml/kg gained significantly more weight at 30 through 90 min than did lungs ventilated at 6 ml/kg. These differences in weight gain were not associated with differences in the evolution of thromboxane B2 in the perfusate. The impact of VT on lung water and outcome in patients with lung injury deserves further study.

Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery.

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.

Experimental traumatic brain injury elevates brain prostaglandin E2 and thromboxane B2 levels in rats.

Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels were measured in rats following experimental traumatic brain injury. Rats (n = 36) were prepared for fluid percussion brain injury under pentobarbital anesthesia. Twenty-four hours later, rats were lightly anesthetized using methoxyflurane, injured (2.3 atm), and killed 5 or 15 min later. Twelve of the rats died before and are not included in the analyses. The following groups were used for data analysis: group I (n = 6) were sham-injured rats prepared for injury but not injured: group II (n = 6) were injured and killed 5 min later; group III (n = 12) were injured and killed 15 min posttrauma. Thirty seconds prior to sacrifice by decapitation into liquid nitrogen, all rats were injected with indomethacin (3 mg/kg, intravenously [IV]) to prevent postmortem PG synthesis. After sacrifice, brains were removed, weighed, and homogenized in a small quantity of phosphate buffer with indomethacin (50 micrograms/ml). PGE2 and TxB2 levels were determined using double-label radioimmunoassays. Posttraumatic convulsions were observed in 5 of 12 rats in group III and these rats were analyzed separately. PGE2 and TxB2 levels increased significantly (p less than 0.05) in both hemisphere and brainstem 5 min posttrauma. Fifteen minutes after injury, both PGE2 and TxB2 levels remained elevated but the levels were lower than at 5 min in the rats that did not exhibit posttraumatic seizures. This decrease in PG levels at 15 min was not observed in the rats that had seizures after injury and both PGE2 and TxB2 levels remained high in hemispheres and brainstem. Thus, fluid percussion brain injury results in substantial elevations in PGE2 and TxB2 levels and posttraumatic seizures exacerbate the observed increases.

Thromboxane generation after thrombin. Protective effect of thromboxane synthetase inhibition on lung fluid balance.

We examined the role of thromboxane in mediating the alterations in pulmonary hemodynamics and in lung fluid and protein exchange after thrombin. Studies were made in control sheep and in sheep pretreated with the thromboxane synthetase inhibitor, Dazoxiben (injection of 10 mg/kg followed by infusion of 4 mg/kg per hr). Thrombin infusion caused an increase in mixed venous and aortic concentrations of thromboxane B2, a stable degradation product of thromboxane A2, whereas the concentrations of 6-keto-PGF1 alpha, a degradation product of prostacyclin, did not change significantly. In sheep pretreated with Dazoxiben, thromboxane B2 concentrations did not increase, indicating effectiveness of the thromboxane synthetase inhibitor. The blood concentrations of 6-keto-PGF1 alpha after thrombin increased in the thromboxane synthetase-inhibited group, indicating shunting towards prostacyclin synthesis. Thrombin in untreated sheep increased pulmonary lymph flow (Qlym) and the lymph protein clearance (Qlym X lymph-to-plasma protein concentration ratio). The increases in lymph parameters were due to an increase in pulmonary vascular permeability to proteins because raising left atrial pressure further increased Qlym but did not change lymph-to-plasma ratio. Dazoxiben prevented the thrombin-induced increase in pulmonary vascular permeability because the increase in left atrial pressure resulted in an increase in Qlym and a decrease in lymph-to-plasma ratio, as was the case after left atrial hypertension in normal animals. Therefore, thrombin results in selective release of thromboxane A2 which precedes the increase in pulmonary vascular permeability. Thromboxane A2 may contribute to the increased permeability after thrombin, since inhibition of thromboxane synthesis prevents the permeability change.

Thromboxane and prostacyclin changes during cardiopulmonary bypass with and without pulsatile flow.

Nonpulsatile cardiopulmonary bypass, in patients with coronary artery disease, produces a significant increase in thromboxane, a potent platelet aggregant and putative coronary vasoconstrictor. Pulsatile flow may decrease the incidence of perioperative infarction and the hormonal stress response to bypass. This study assessed the effect of pulsatile blood flow on plasma thromboxane and prostacyclin profiles during cardiopulmonary bypass by serial measurement of their stable metabolites, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Two groups of eight patients each were studied before, during, and after cardiopulmonary bypass. Eight patients had routine (nonpulsatile) bypass and eight had pulsatile flow. In the nonpulsatile group, the TxB2 concentration significantly increased during bypass (65 +/- 39 to 1,224 +/- 306 pg/ml, p less than 0.01) and rapidly returned to control. Prostacyclin also rose (53 +/- 20 to 613 +/- 132 pg/ml, p less than 0.01). In the pulsatile group, TxB2 rose during bypass (53 +/- 18 to 693 +/- 130 pg/ml, p less than 0.01), but peak concentration was significantly lower than in the nonpulsatile group (1,224 +/- 306 versus 693 +/- 130 pg/ml, p less than 0.05). Prostacyclin rose sharply during cardiopulmonary bypass in the pulsatile group (53 +/- 22 to 1,033 +/- 136 pg/ml, p less than 0.01) and was higher than in the nonpulsatile group (1,033 +/- 136 versus 325 +/- 33 pg/ml, p less than 0.01). There were no intragroup differences of plasma hemoglobin, hematocrit, or platelet count. These data demonstrate that pulsatile flow significantly alters prostacyclin and thromboxane profiles during cardiopulmonary bypass and favors production of the coronary vasodilator and platelet disaggregant prostacyclin. This may be an important factor in some of the clinical advantages previously reported with this modality.