Biomedical subjects

S Gando

Publications and source records attributed to S Gando.

At least 37 records · Page 2Linked to original sources

PubMed2000

Pentobarbital inhibits apoptosis in neuronal cells.

OBJECTIVE: Previous reports have demonstrated that barbiturates have a protective effect against cerebral ischemia, although the mechanisms are incompletely understood. Recently, it has been suggested that apoptosis is involved in ischemic neuronal death. This study examined the effect of pentobarbital on neuronal apoptosis. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: PC12 cells derived from rat pheochromocytoma as a model of neuronal tissue. INTERVENTIONS: Apoptosis was induced by depriving serum from the cell culture medium. Effect of pentobarbital (0.5, 5, 50 microg/mL) was evaluated. MEASUREMENTS AND MAIN RESULTS: First, electrophoresis of DNA and fluorescence microscopic examination were performed to ascertain whether apoptosis was really induced after serum deprivation in our cells. Second, the effect of pentobarbital on cytotoxicity (evaluated by a leakage assay of lactic dehydrogenase) was evaluated. Third, the percentage of apoptotic cells was calculated by measuring cellular DNA content with flow cytometry. Calculation of the percentage of apoptotic cells was based on cumulative frequency curves of the appropriate DNA histograms. DNA electrophoresis exhibited a typical ladder pattern from the first day after the induction of apoptosis. The cells with chromatin condensation and/or fragmentation increased day by day after depriving serum in fluorescence microscopic examination. Four days after the induction of apoptosis, cytotoxicity without pentobarbital was 53.9 +/- 24.3% (mean +/- SD). Pentobarbital significantly inhibited cell death in a dose-dependent fashion. The percentage of apoptotic cells without pentobarbital was 94.9 +/- 6.3% 4 days after the induction of apoptosis. The treatment with 50 microg/mL pentobarbital significantly decreased the percentage of apoptotic cells to 61.8 +/- 21.3%. CONCLUSIONS: Our data indicate that pentobarbital inhibits apoptosis induced by serum deprivation in PC12 cells.

Apoptosis↗

PubMed1999

Tissue factor and tissue factor pathway inhibitor levels during and after cardiopulmonary resuscitation.

Disseminated intravascular coagulation frequently occurs after global ischemia and reperfusion due to cardiac arrest. The present study was performed to demonstrate the role of tissue factor for coagulation pathway activation, as well as to investigate the precise time course of tissue factor pathway inhibitor (TFPI) during and after cardiopulmonary resuscitation (CPR). Thirty-two of out-of-hospital cardiac arrest patients were classified into two groups, those who achieved return of spontaneous circulation (ROSC) (n=13) and those without ROSC (n=19). Ten normal healthy volunteers served as control subjects. Serial levels of tissue factor and TFPI were measured during and after cardiac arrest and CPR. In patients with ROSC, cardiac arrest and CPR led to persistent increases in the levels of tissue factor that peaked 6 hours after arrival at the Emergency Department. Tissue factor levels in patients without ROSC also showed marked elevations compared to those of the control subjects. In both groups, the levels of TFPI were significantly lower than those in the control subjects. However, we could not find differences in the levels of the two markers between the patients with ROSC and those without ROSC. In conclusion, we demonstrated persistent elevation of the tissue factor levels associated with low TFPI during and after CPR in patients with out-of-hospital cardiac arrest. These results indicate the activation of the extrinsic coagulation pathway without adequate TFPI generation, which may contribute to thrombin activation and fibrin formation after whole-body ischemia and reperfusion.

Adult↗

PubMed1999

Diabetes-induced down-regulation of beta1-adrenoceptor mRNA expression in rat heart.

The present study addressed the question of whether the number of myocardial beta-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabetes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [3H]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one} showed that the density of beta-adrenoceptors fell by 50% with no change in affinity in diabetic rat ventricular myocardium compared with age-matched control myocardium. The relative content of beta1-adrenoceptor mRNA in diabetic myocardium also was reduced from the control level by 57%, as determined by northern blot analysis. The reductions in myocardial beta-adrenoceptor number and beta1-adrenoceptor mRNA observed in diabetes were prevented by insulin therapy. These data indicate that the diminished density of myocardial beta-adrenoceptors in diabetes occurred, at least in part, at the mRNA level.

Animals↗

PubMed1999

Therapeutic strategy of perioperative use of percutaneous cardiopulmonary bypass support (PCPS) for adult cardiac surgery.

SUBJECT AND METHOD: Percutaneous cardiopulmonary bypass support is beneficial for patients with circulatory collapse. However, therapeutic strategies of percutaneous cardiopulmonary bypass support for post-cardiotomy LOS have not been determined. We reviewed 9 patients undergoing cardiac surgery and treated with percutaneous cardiopulmonary bypass support to determine an adequate strategy for perioperative use of percutaneous cardiopulmonary bypass support. Patients included 8 males and 1 female with a mean age of 56.4 +/- 3.9 years. Six patients with IHD underwent CABG for 5 and CABG + MVR for 1 patient and 3 patients with valvular disease underwent AVR, AVR + MVR, and Ross operation respectively. Indication for percutaneous cardiopulmonary bypass support was post-cardiotomy LOS in 7 and preoperative cardiogenic shock in 2 patients. All patients underwent IABP associated with percutaneous cardiopulmonary bypass support. Systemic blood pressure was regulated to 100-120 mmHg by percutaneous cardiopulmonary bypass support flow and with minimum inotropic supports. RESULTS: Six of 9 patients (66.7%) were weaned from percutaneous cardiopulmonary bypass support and 5 patients were discharged. Five of 6 patients (83.3%) with IHD were weaned from percutaneous cardiopulmonary bypass support compared to 1 of 3 patients (33.3%) (p = 0.134) with valvular disease. Hemodynamic conditions in patients weaned from percutaneous cardiopulmonary bypass support were markedly improved within 40 hours of the introduction of percutaneous cardiopulmonary bypass support (mean percutaneous cardiopulmonary bypass support running time: 23.9 +/- 5.5 hrs). In contrast, those unable to be weaned from percutaneous cardiopulmonary bypass support (mean percutaneous cardiopulmonary bypass support running time: 84.3 +/- 6.3 hrs) showed no improvement and developed major complications such as cerebral damage or multiorgan failure. CONCLUSIONS: Perioperative use of percutaneous cardiopulmonary bypass support may be more effective for patients undergoing coronary artery surgery. Limited use of percutaneous cardiopulmonary bypass support within 48 hours may be applicable for post-cardiotomy patients.

Adult↗

PubMed1999

Alterations of soluble L- and P-selectins during cardiac arrest and CPR.

OBJECTIVE: To investigate the relationship between cytokines and the inflammatory responses in patients with out-of-hospital cardiac arrest, we examined the changes of cytokines as well as alterations in the markers of neutrophil activation, platelet and endothelial activation, and endothelial injury. DESIGN: Prospective, cohort study. SETTING: General intensive care unit of a tertiary care center. PATIENTS AND PARTICIPANTS: 26 out-of-hospital cardiac arrest patients were classified into two groups: those who achieved return of spontaneous circulation (ROSC) (n = 10) and those with no ROSC (n = 16). Eight normal healthy volunteers served as control subjects. MEASUREMENTS AND RESULTS: Serial levels of soluble L-selectin (sL-selectin), soluble P-selectin (sP-selectin), neutrophil elastase, and soluble thrombomodulin were measured during and after cardiopulmonary resuscitation (CPR). Serial levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) were also measured. We could not find any elevations in either cytokine during the study period. In both groups, sP-selectin levels were significantly higher than those in control subjects from the time of arrival at the emergency department to 24 h after admission. sL-selectin levels in the two groups were markedly lower compared to those in control subjects at all sampling points. In patients with ROSC, cardiac arrest and CPR led to an increase in the levels of neutrophil elastase and soluble thrombomodulin that peaked 6 h or 24 h after arrival at the emergency department. No statistical differences in the levels of the two selectins, neutrophil elastase, and soluble thrombomodulin between the two groups were found during CPR. CONCLUSIONS: Out-of-hospital cardiac arrest and CPR induces platelet, neutrophil, and endothelial activation and is associated with endothelial injury. Inflammatory cytokines may not have an important role in human whole-body ischemia-reperfusion injury.

Aged↗

PubMed1999

Cardiac profile of EGIS-9377, a novel cardiotonic agent as a Ca2+ sensitizer with bradycardiac activity.

The cardiac profile of EGIS-9377 ¿2-(1-methylthio)-5-(2-morpholinoethylamino)-8,9-dihydro-7H-thi opyrano[3,2-d][1,2,4]triazolo[1,5-a]pyrimidine dihydrochloride¿, a newly synthesized cardiotonic agent, was compared with those of pimobendan and isoprenaline in cardiac preparations isolated from guinea pigs. The positive inotropic potency and efficacy of EGIS-9377 were equal to those of pimobendan in electrically paced papillary muscles, with each agent maximally increasing force of contraction by 30-35% of the maximum effect of isoprenaline. The positive inotropic effects of EGIS-9377 and pimobendan were accompanied by an increase in the relaxation time of the isometric contraction curve, whereas that of isoprenaline was associated with an abbreviation of this parameter. Pimobendan significantly increased the spontaneously beating frequency of right atria, and its positive chronotropic effect amounted to 40% of the maximum effect of isoprenaline. In contrast, EGIS-9377 exerted a significant negative chronotropic action, which resulted in a 30% decrease in the basal frequency. In beta-escin-skinned trabecular muscles, both EGIS-9377 and pimobendan substantially enhanced contractions induced by Ca2+. EGIS-9377 at concentrations to cause a significant negative chronotropic action produced a marked prolongation of action potential duration (APD) in guinea pig papillary muscle and greatly inhibited the delayed rectifier potassium current (I(K)) in guinea pig ventricular single cells. This suggests that the negative chronotropic effect of EGIS-9377 may, at least in part, be due to the prolongation of APD as a result of the I(K) inhibition. The present results indicate that EGIS-9377 efficiently increases myocardial contractile force possibly due to its Ca2+ -sensitizing activity, and yet produces a substantial negative chronotropic action. This cardiac profile of EGIS-9377 is suggested to be a clinically favorable feature compared with the inotropic agents having cyclic AMP generation or phosphodiesterase inhibition as their action mechanisms.

Animals↗

PubMed1999

Disseminated intravascular coagulation and sustained systemic inflammatory response syndrome predict organ dysfunctions after trauma: application of clinical decision analysis.

OBJECTIVE: To determine the accuracy of disseminated intravascular coagulation (DIC) and sustained systemic inflammatory response syndrome (SIRS) in predicting posttrauma multiple organ dysfunction syndrome (MODS) and to find a simple laboratory test for detecting MODS. SUMMARY AND BACKGROUND DATA: In trauma patients, the duration of SIRS is the main determinant for MODS and outcome. METHODS: One hundred thirty-six patients with trauma were classified into subgroups according to the duration of SIRS: patients without SIRS (n = 27), patients with SIRS for <2 days (n = 52), and patients with SIRS for > or =3 days (n = 57). Platelets and five coagulation and fibrinolytic laboratory tests for diagnosing DIC were measured on the day of admission and on days 1 through 4 after admission. Simultaneously, the DIC score was determined. The diagnostic accuracy of DIC and sustained SIRS for the prediction of MODS was determined using likelihood ratios. A receiver operating characteristic curve of platelet counts for predicting MODS was also constructed. RESULTS: Platelet counts showed significant differences among the three groups. The incidence of DIC, acute respiratory distress syndrome, and MODS was significantly higher in patients with SIRS for > or =3 days compared with those in the other groups, and they had a poor outcome. Likelihood ratios of DIC and SIRS for > or =3 days for predicting posttrauma MODS were 11.6 and 6.25, respectively. Platelet counts (80 x 10(9)/l) on day 1 had a sensitivity of 83.3% and a specificity of 100% for predicting MODS. CONCLUSIONS: Disseminated intravascular coagulation and sustained SIRS are strong determinants for posttrauma MODS. This retrospective analysis supports the possibility that platelet counts can be used as a simple laboratory test for predicting MODS. This hypothesis requires proof using a prospective clinical survey.

Adult↗

PubMed1999

End-tidal carbon dioxide and resuscitation.

In this review, we attempted to summarize the effectiveness and the limitation of end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. End-tidal carbon dioxide can be an indicator of the real return of spontaneous circulation and can also be an indicator of the effectiveness of cardiac massage. We cannot, however, estimate the prognosis of cardiopulmonary resuscitation from the end-tidal carbon dioxide value. We concluded that cardiopulmonary resuscitation should never be abandoned for the sole reason that the end-tidal carbon dioxide value is low.

Journal Article↗

PubMed1999

Coagulofibrinolytic changes after isolated head injury are not different from those in trauma patients without head injury.

BACKGROUND: To test the hypothesis that tissue factor release, thrombin activation, fibrin formation, and fibrinolysis after an isolated head injury are equal to those in patients without head injury, as well as to investigate the precise time course of the coagulation and fibrinolytic abnormalities after head injury, we performed prospective and retrospective studies. METHODS AND RESULTS: In the prospective study, 5 patients with isolated head injury and 11 trauma patients without head injury took part in this study. Tissue factor antigen concentration, prothrombin fragment F1+2, thrombin antithrombin complex, fibrinopeptide A, and fibrin degradation products (D-dimer) were measured on the day of admission, and days 1, 2, 3, and 4 after admission. The levels of all five hemostatic molecular markers were markedly elevated on the day of admission, and then gradually decreased to day 4. The levels and the time course of these hemostatic markers in patients with isolated head injury were not different from those in the control patients. The same incidence of disseminated intravascular coagulation between the two groups was also observed. In the retrospective study, the records of fibrinopeptide Bbeta15-42, plasmin antiplasmin complex, plasminogen activator inhibitor-1 antigen concentration (PAI-1 antigen), and PAI-1 activity in 76 trauma patients were reviewed. On the basis of the exclusion criteria, 9 patients with isolated head injury and 30 control patients were selected for the study group. Fibrinopeptide Bbeta15-42 and plasmin antiplasmin complex markedly elevated on the day of admission, then decreased on day 1, and tended to increase to day 5. Markedly elevated PAI-1 antigen and PAI-1 activity on the day of admission significantly decreased on day 1 and recovered to the normal values on day 5. The changes of these molecular markers in patients with isolated head injury were equal to those in the control patients. CONCLUSION: We systematically elucidated the time course of coagulation and fibrinolysis after isolated head injury. We further demonstrated that changes in coagulofibrinolytic and antifibrinolytic systems in patients with isolated head injury are not different from those in patients without head injury.

Adult↗

PubMed1999

Systemic activation of tissue-factor dependent coagulation pathway in evolving acute respiratory distress syndrome in patients with trauma and sepsis.

BACKGROUND: Extravascular coagulation and fibrin deposition coupled with perturbations of intravascular coagulation occurs in association with acute respiratory distress syndrome (ARDS). To evaluate the pathogenetic role of an extrinsic coagulation pathway in the intravascular coagulation of ARDS patients and to explore the time course of the changes of tissue factor levels, platelet counts, and disseminated intravascular coagulation (DIC), we performed a prospective cohort study. METHODS: The study subjects consisted of 113 patients: 27 patients with ARDS, 31 patients at risk for but not developing the syndrome, and 55 patients without ARDS. According to the underlying disease, the patients were further subdivided into two groups: patients with trauma (n = 76) and patients with sepsis (n = 37). Ten normal healthy volunteers served as control subjects. Plasma tissue factor antigen (tissue factor) levels and platelet counts were measured on the day of admission and on days 1 through 4 after admission. Simultaneously, the DIC scores were determined. RESULTS: The values of tissue factor in the patients with ARDS were significantly more elevated than those measured in the other two groups (p < 0.001) and control subjects (p < 0.001) on the day of admission. The values continued to be markedly high up to day 4 of admission. On the day of admission, the platelet counts in the ARDS patients showed significantly lower values (p < 0.05) than those in the other two groups. The incidence of DIC and the DIC scores in ARDS patients were significantly higher than those in the other two groups. The tissue factor levels (r(s) = 0.428, p < 0.0001) and DIC scores (r(s) = 0.357, p < 0.0002) correlated significantly with Lung Injury Score. When the patients were subdivided into two subgroups, i.e., trauma and sepsis, some differences of the tissue factor levels were noted between the two groups. CONCLUSION: We demonstrated that tissue-factor dependent coagulation pathway of plasma is extensively activated in patients with ARDS, followed by intravascular coagulation and platelet consumption. We further provide precise information on the time course of tissue factor levels and DIC in patients with ARDS and those at risk for developing this syndrome.

APACHE↗

PubMed1998

Pharmacokinetics and clearance of ganciclovir during continuous hemodiafiltration.

OBJECTIVE: To evaluate the ganciclovir pharmacokinetics and clearance during continuous venovenous hemodiafiltration. DESIGN: Case report. SETTING: General intensive care unit of a tertiary care emergency department. PATIENTS: A 63-yr-old female who has a history of active behçet's disease that has been controlled with oral prednisolone, and who has chronic renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A 5-mg/kg dosage of ganciclovir was administered intravenously over a 60-min period under continuous venovenous hemodiafiltration. Samples from the arterial and venous blood catheters and from the ultradiafiltrate were collected over the next 12 hrs to calculate pharmacokinetic parameters and clearance of hemodiafiltration. The pharmacokinetic parameters were as follows: half-life of elimination phase 12.6 hrs; total clearance 0.55 mL/min/kg; and volume distribution of steady state 27.07 L. The clearance of hemodiafiltration was 0.63 mL/min/kg. CONCLUSION: Continuous venovenous hemodiafiltration is effective in removing ganciclovir from the blood.

Antimetabolites↗

PubMed1998

Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock.

OBJECTIVES: To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. DESIGN: Prospective observational study. SETTING: General intensive care unit. PATIENTS: Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). CONCLUSIONS: We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.

Adult↗

PubMed1998

Significant correlations between tissue factor and thrombin markers in trauma and septic patients with disseminated intravascular coagulation.

To determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 +/- 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

APACHE↗

PubMed1997

Platelet activation with massive formation of thromboxane A2 during and after cardiopulmonary resuscitation.

OBJECTIVE: Hypoxia and ischemia cause endothelial cell damage with consequent platelet activation. The hypothesis that human cardiac arrest accelerates platelet activation and the formation of prostanoids was tested. DESIGN: Prospective, observational cohort study. SETTING: Emergency Department and general Intensive Care Unit in a city hospital. INTERVENTIONS: Basic and advanced life support. PATIENTS AND PARTICIPANTS: Forty-seven out-of-hospital cardiac arrest patients. The patients were classified into two groups, those who were resuscitated (n = 18) and those who died (n = 29). MEASUREMENTS AND RESULTS: Serial levels of platelet aggregation, thromboxane B2 (TXB2), 11-dehydro-TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured. The results of measurements and demographic data were compared between the groups. Platelet counts decreased at the end of cardiopulmonary resuscitation (CPR), the decrease of the platelet counts showed statistical significance especially in the patients who died (p < 0.001). Platelet aggregation induced by adenosine diphosphate, epinephrine and collagen decreased to the lower limits of normal during and after CPR. Although high values of TXB2 and 11-dehydro-TXB2 continued throughout the study period in the resuscitated patients, 6-keto-PGF1 alpha decreased to the normal range (22.7 +/- 3.6 pg.ml-1. p < 0.05 at -24 h after arrival at the Emergency Department. CONCLUSIONS: Platelet activation with the massive formation of thromboxane A2 (TXA2) occurs in patients with out-of-hospital cardiac arrest. Successful resuscitation is not associated with the balanced production of PGI2 against the TXA2 formation.

Aged↗

PubMed1997

Ionized hypocalcemia during out-of-hospital cardiac arrest and cardiopulmonary resuscitation is not due to binding by lactate.

OBJECTIVE: To determine the relationship between ionized calcium concentrations and blood lactate levels during cardiac arrest and cardiopulmonary resuscitation (CPR). DESIGN: A prospective cohort study. SETTING: Emergency department (ED) and general intensive care unit in a city hospital (tertiary care center). PATIENTS AND PARTICIPANTS: 32 patients with out-of-hospital cardiac arrest; 14 of the patients had a return of spontaneous circulation (ROSC) and 18 of the patients died. INTERVENTIONS: Basic and advanced life support. MEASUREMENTS AND RESULTS: Concentrations of ionized and total calcium, bicarbonate, lactate, and pyruvate and pH were simultaneously determined immediately upon arrival at the ED, and at 30 and 60 min. Upon arrival at the ED, all patients had ionized hypocalcemia (1.09 +/- 0.02 mmol/l). Ionized and total calcium concentrations progressively decreased during and after CPR, but pH and bicarbonate concentrations did not show any significant changes. In patients who had ROSC, a significant, but perhaps not clinically relevant, relationship was observed between the ionized calcium concentrations and pH (r2 = 0.152, p = 0.0117). In the patients who died, there were significant correlations between ionized calcium and pH (r2 = 0.382, p = 0.0001) and bicarbonate concentrations (r2 = 0.298, p = 0.0006). No definite correlations were demonstrated when comparing ionized calcium concentrations with lactate and pyruvate concentrations. CONCLUSIONS: Ionized hypocalcemia during out-of-hospital cardiac arrest and CPR is not due to binding by both lactate and pyruvate, but may be partly due to complexing by bicarbonate, with some modifications due to variations in pH.

Aged↗

PubMed1997

Participation of tissue factor and thrombin in posttraumatic systemic inflammatory syndrome.

OBJECTIVE: To determine the roles of tissue factor and thrombin on the systemic inflammatory response syndrome (SIRS) in posttrauma patients, as well as to investigate the relationship between SIRS and sepsis. DESIGN: Prospective, cohort study. SETTING: General intensive care unit of a tertiary care emergency department. PATIENTS: Forty trauma patients were classified into subgroups, according to the duration of SIRS: non-SIRS patients (n = 9); patients with SIRS for < 2 days (n = 15); and patients with SIRS for > 3 days (n = 16). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration, prothrombin fragment F1+2, thrombin antithrombin complex, fibrinopeptide A, and cross-linked fibrin degradation products (D-dimer) were measured on the day of admission, and on days 1 through 4 after admission. Simultaneously, the number of SIRS criteria that the patients met and the disseminated intravascular coagulation score were determined. The results of these measurements, frequency of acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome, sepsis, and outcome were compared among the groups. The values of all five hemostatic molecular markers in the patients with SIRS for > 3 days were significantly more increased than those molecular marker values measured in the other groups on the day of admission. These values continued to be markedly high up to day 4 of admission. The occurrence rates of disseminated intravascular coagulation in these patient groups were significantly higher than those rates in the other two groups (p = .0001), and the disseminated intravascular coagulation scores did not improve during the study period. The occurrence rates of ARDS (p < .05) and multiple organ dysfunction syndrome (p < .01) were higher in patients with SIRS for > 3 days compared with those rates in the other groups, and the patients with SIRS for > 3 days had a poor outcome. No significant difference was noted in the frequency of sepsis among the groups. CONCLUSIONS: Sustained SIRS is the main determinant for ARDS, multiple organ dysfunction syndrome, and outcome in posttrauma patients. Disseminated intravascular coagulation associated with massive thrombin generation and its activation is involved in the pathogenesis of sustained SIRS. Sepsis has a small role in early posttrauma multiple organ dysfunction syndrome.

Abbreviated Injury Scale↗

PubMed1997

Increased neutrophil elastase, persistent intravascular coagulation, and decreased fibrinolytic activity in patients with posttraumatic acute respiratory distress syndrome.

BACKGROUND: To investigate the role of plasma neutrophil elastase (elastase-alpha1-proteinase inhibitor complex), plasminogen activator inhibitor-1 (PAI-1), and disseminated intravascular coagulation (DIC) in patients with posttraumatic acute respiratory distress syndrome (ARDS) and to explore the time course of the changes of these factors after trauma, we performed a prospective case-control study. METHODS: The study subjects consisted of 41 trauma patients, 5 with ARDS, 7 at risk for but not developing the syndrome, and 29 control patients without or with no risk for ARDS. Plasma neutrophil elastase, PAI-1 activity, and PAI-1 antigen concentration were measured on the day of the injury and on days 1, 3, and 5 after admission. DIC was measured on the basis of the DIC score. The results of these measurements and demographic data were compared among the three groups. RESULTS: Neutrophil elastase, PAI-1 activity, and PAI-1 antigen concentration for the ARDS patients continued to be markedly high until the fifth day of admission, and the values on the fifth day were significantly higher than those of the other two groups. All patients with ARDS developed DIC. A decrease in the DIC score was found for the control patients and also for the patients at risk for ARDS; however, for the patients with ARDS, the DIC score did not improve during the study period (p = 0.5809). CONCLUSION: We provide precise information on the time course of neutrophil elastase, PAI-1, and DIC in trauma patients with ARDS and those at risk of developing this syndrome. Neutrophil activation and persistent intravascular coagulation as well as impaired fibrinolysis may play a role in the pathogenesis of posttraumatic ARDS.

Adult↗

PubMed1997

Massive fibrin formation with consecutive impairment of fibrinolysis in patients with out-of-hospital cardiac arrest.

Hypoxia and ischaemia influence blood coagulation and fibrinolysis. This study has been made to determine whether human cardiopulmonary arrest causes fibrin formation and reduction of fibrinolysis. Serial levels of fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimer, tissue plasminogen activator antigen concentration (t-PA antigen), t-PA activity, plasminogen activator inhibitor-1 antigen concentration (PAI-1 antigen), and PAI-1 activity were determined in 63 patients with out-of-hospital cardiopulmonary arrest. In the resuscitated patients, the markedly elevated FPA (194.8 +/- 54.2 ng/ml) at the beginning of cardiopulmonary resuscitation (CPR) significantly decreased to 32.4 +/- 9.1 ng/ml at 24 h after admission (p < 0.01), however, this was still about 20 times that of the normal controls. FPB beta 15-42 and D-dimer increased from the start of CPR to 60 min (189.3 +/- 97.4 ng/ml; p < 0.01 and 7726 +/- 3556 ng/ml; p < 0.001, respectively), and then decreased at 24 h after arrival at the Emergency Department (40.4 +/- 11.1 ng/ml and 5434 +/- 1049 ng/ml, respectively). At 30 min after arrival, FPA and FPB beta 15-42 significantly differed between the resuscitated patients and the patients who died (p < 0.001 and P < 0.05, respectively). Although t-PA antigen and t-PA activity was elevated at the time of arrival, 24 h thereafter, no-t-PA activity was detected. At 24 h after admission, PAI-1 antigen and PAI-1 activity were significantly increased (472.2 +/- 145.5 ng/ml; p < 0.001 and 103.6 +/- 36.1 IU/ml; p < 0.001, respectively). In conclusion, during and after CPR in patients with out-of-hospital cardiac arrest, massive fibrin generation with consecutive impairment of fibrinolysis were observed. These fibrin-mediated events may have some role in the derangement of vital organ function after cardiac arrest.

Aged↗