Biomedical subjects

S Gando

Publications and source records attributed to S Gando.

At least 55 records · Page 3Linked to original sources

PubMed1997

Impaired contractile response to beta adrenoceptor stimulation in diabetic rat hearts: alterations in beta adrenoceptors-G protein-adenylate cyclase system and phospholamban phosphorylation.

The aim of this study was to explore the cellular mechanisms underlying the impaired contractile response to beta adrenoceptor stimulation in diabetic hearts. Chronic diabetes was induced in rats by a streptozotocin injection. Four to six weeks later, papillary muscles isolated from diabetic hearts exhibited marked reductions in the positive inotropic responses to isoproterenol, norepinephrine and epinephrine. The contractile responses to forskolin, 3-isobutyl-1-methylxanthine and dibutylic cyclic AMP were also prominently depressed. The density of beta adrenoceptors was decreased by 50%. However, competitive binding studies with isoproterenol showed no difference in the proportion of beta adrenoceptors with high-affinity binding between control and diabetic myocardial membranes. Determination of the levels of the alpha subunits of Gs and Gi by immunoblotting revealed markedly less expression of Gi in diabetic myocardium. The abilities of isoproterenol, sodium fluoride, 5'-guanylyl imidodiphosphate and forskolin to stimulate adenylate cyclase were preserved well in membranes prepared from diabetic hearts. Nevertheless, neither stimulation of beta adrenoceptors with isoproterenol nor direct activation of adenylate cyclase with forskolin evoked any significant increase in the degree of phosphorylation of phospholamban in diabetic hearts. These results suggest that impaired contractile response to beta adrenoceptor stimulation is not caused by an alteration in the beta adrenoceptors-Gs-adenylate cyclase system, but is possibly caused by an alteration in cellular function beyond the step of adenylate cyclase activation.

1-Methyl-3-isobutylxanthine↗

PubMed1996

Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome.

To evaluate the role of disseminated intravascular coagulation (DIC) and to determine the influence of antithrombin, protein C, and plasminogen activator inhibitor 1 on multiple organ dysfunction syndrome (MODS) and outcome in patients with systemic inflammatory response syndrome (SIRS), we made a prospective cohort study. The study subjects consisted of thirty-five patients who exhibited two or more of the conditions of SIRS for more than three consecutive days. They were classified into subgroups of survivors (n = 13) and nonsurvivors (n = 22). The global coagulation and fibrinolytic markers, antithrombin, protein C, and plasminogen activator inhibitor 1 were measured on the day of the diagnosis of SIRS, and also on the 1st, 3rd, and 5th days. The results of these measurements, demographic data, criteria of severity, incidence of MODS were compared between the subgroups. For prediction of patient's death, a receiver operating characteristic (ROC) curve analysis was made. DIC was frequently associated with SIRS patients (29/35, 82.9%). A significant decrease in the DIC score was found in the survivors (p = 0.0001). None of them suffered from DIC on the 5th day. In the nonsurvivors, low levels of protein C and antithrombin and markedly high values of plasminogen activator inhibitor 1 continued up to the 5th day, no improvement of the DIC was observed during the study period and the number of the dysfunctioning organs were significantly higher than in the survivors. Plasminogen activator inhibitor 1 on the 5th day had prognostic value for the prediction of death on the SIRS patients. In conclusion, DIC occurs commonly in patients with SIRS and may be the main determinant for the outcome of these patients. Changes in antithrombin, protein C, and plasminogen activator inhibitor 1 are one of the aggravating factors of MODS. Furthermore, plasminogen activator inhibitor 1 is a good predictor of death in these patients.

APACHE↗

PubMed1996

[Two cases of severe cytomegalovirus pneumonitis treated with permissive hypercapnia].

Two patients with severe cytomegalovirus (CMV) pneumonitis were treated with permissive hypercapnia. Case 1 was a 66-year-old male who suffered ventricular septal perforation caused by acute myocardial infarction. Case 2 was a 54-year-old male who sustained a blunt chest injury. In both cases, hypoxia with reduction of lung compliance developed after their operations. They were mechanically ventilated and we limited their peak inspiratory pressure, disregarding hypercapnia (i.e. permissive hypercapnia). During permissive hypercapnia, the maximum arterial partial pressure of carbon dioxide (PaCO2) was 96 mmHg in case 1 and 141 mmHg in case 2. Duration of hypercapnia (PaCO2 > 50mmHg) was 22 days in case 1 and 29 days in case 2. The patients were weaned from the respirator after two months of mechanical ventilation. In conclusion, the permissive hypercapnia was a useful method in the treatment of severe CMV pneumonitis.

Aged↗

PubMed1995

Cytokines, soluble thrombomodulin and disseminated intravascular coagulation in patients with systemic inflammatory response syndrome.

To investigate the relationships between tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), soluble thrombomodulin (TM), and disseminated intravascular coagulation (DIC) in patients with systemic inflammatory response syndrome (SIRS), twenty-nine SIRS patients were classified into three groups; 4 patients without DIC, 8 DIC patients who recovered, and 17 DIC patients who did not recover. Serum TNF, IL-1 beta, and soluble TM were measured on the day of the diagnosis of SIRS, and also on the 1st, 3rd, 5th days. All of the DIC patients had multiple organ dysfunction syndrome (MODS) and the number of the dysfunctioning organs showed significant differences between the groups (p = .0017). All of the patients who did not recover from DIC died. The serum soluble TM level was higher in the patients without DIC recovery than in either the DIC recovery patients or the non DIC patients throughout the study period. In DIC patients who did not recover, there were significant correlations between soluble TM and TNF (r2 = 0.205, p = .0003) or IL-1 beta (r2 = 0.157, p = .0036). In conclusion, the DIC being associated with endothelial injury is an important pathogenetic factor for MODS and is a main determinant of the outcome of SIRS patients. TNF and IL-1 beta might be involved in the cause of this endothelial injury. The soluble TM is a good predictor of organ dysfunction and also of a poor prognosis.

Adult↗

PubMed1995

Endothelin-1 does not phosphorylate phospholamban and troponin I in intact beating rat hearts.

To determine a role of phosphorylation of specific cardiac regulatory proteins in the positive inotropic effect of endothelin-1, we examined phosphorylation of sarcoplasmic reticulum and myofibrillar proteins in perfused beating rat hearts treated with endothelin-1. In parallel experiments, the effects of isoprenaline and phorbol-12,13-dibutyrate (PDB) on protein phosphorylation were also tested. In 32Pi-labeled hearts, perfusion with isoprenaline (100 nM) caused 4.4- and 10.4-fold increases in the degree of phosphorylation of phospholamban in sarcoplasmic reticulum and of troponin I in myofibrils, respectively. In contrast, neither endothelin-1 (100 nM) nor PDB (1 microM) significantly changed the phosphorylation state of these proteins. These findings provide evidence that phosphorylation of major cardiac regulatory proteins is not responsible for the positive inotropic action of endothelin-1.

Animals↗

PubMed1995

Increased neutrophil elastase release in patients with cardiopulmonary arrest: role of elastase inhibitor.

OBJECTIVE: To determine the changes in neutrophil elastase levels in patients with cardiac arrest occurring outside the hospital and to evaluate the effects of urinastatin on these changes and on the clinical outcomes of the patients. DESIGN: Prospective study. SETTING: The Emergency Department and a general ICU in the tertiary care city hospital. PATIENTS: Of the 40 patients who had an out-of-hospital cardiac arrest, 38 of the cases were randomized into 2 groups, with 2 cases being excluded because of contradiction to protocol. The control and urinastatin groups consisted of 20 and 18 patients, respectively. INTERVENTIONS: Control patients were treated by standard cardiopulmonary resuscitation (CPR) procedures. Patients in the urinastatin group were administered a 100,000 U dose of urinastatin immediately after arrival at the Emergency Department and three 100,000 U doses at 8 h intervals, within the first 24 h after resuscitation. MEASUREMENTS AND MAIN RESULTS: At the time of arrival at the emergency room (before administration of urinastatin), and at 30 min, 60 min, and 24 h after, the plasma levels of neutrophil elastase and blood gas levels were determined. Concerning the baseline characteristics of patients, causes of cardiac arrest, time duration of pre-hospital care and treatments given during CPR, there was no difference detected between the control and urinastatin groups. In addition, the pH and PaO2 values showed no differences. Neutrophil elastase values had already increased by the time of arrival and continued to do so until 60 min; at 24 h after admission, markedly higher values were obtained. These values were significantly higher in the non-resuscitated cases than in the resuscitated ones. Administration of urinastatin significantly suppressed this increase at 24 h, but did not improve the clinical outcomes, including resuscitation rate and survival rate. CONCLUSIONS: Accompanying cardiopulmonary arrest and resuscitation, neutrophils are activated and elastase is released. Elevated elastase level is associated with poorer prognosis. Urinastatin can suppress the release of elastase, when utilized at the dose described in this study, did not improve the clinical outcomes of patients who had suffered an out-of-hospital cardiac arrest.

Aged↗

PubMed1995

Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated intravascular coagulation: relationship to multiple organ dysfunction syndrome.

OBJECTIVES: a) To investigate the relationships between tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator inhibitor-1, and disseminated intravascular coagulation (DIC); b) to determine the influence of DIC on the mortality rate, adult respiratory distress syndrome (ARDS), and multiple organ dysfunction syndrome; and c) to find a useful prognostic index for outcome. DESIGN: Prospective, case-control study. SETTING: General intensive care unit (tertiary care center) in a city hospital serving a population of 1.5 million people. PATIENTS: Fifty-eight trauma patients; 22 of the patients with DIC and 36 of the patients without DIC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: TNF-alpha, IL-1 beta, plasminogen activator inhibitor-1 activity, and plasminogen activator inhibitor-1 antigen concentration were measured on the day of the injury, and on days 1, 3, and 5 after admission. The results of these measurements, demographic data, severity of illness score, mortality rate in the intensive care unit and frequencies of ARDS, multiple organ dysfunction syndrome, and sepsis were compared according to the occurrence of DIC. DIC patients were classified into subgroups of survivors and nonsurvivors, and the changes in plasminogen activator inhibitor-1 between subgroups were studied. The Acute Physiology and Chronic Health Evaluation II scores, the Injury Severity Scores, and the frequency of ARDS and multiple organ dysfunction syndrome were higher in the DIC patients. The mortality rate of the DIC patients was higher than the rate of the non-DIC patients (59.0% vs. 13.8%; p = .0009). TNF-alpha and IL-1 beta concentrations increased more in the DIC patients than in the non-DIC patients. Plasminogen activator inhibitor-1 activity and plasminogen activator inhibitor-1 antigen concentrations in the DIC patients, especially those values in the nonsurvivors, continued to be markedly high up to day 5 of admission. The most favorable prognostic value of plasminogen activator inhibitor-1 for the prediction of death in all of the trauma patients and the DIC patients was determined on days 3 and 5, respectively. No significant correlation was noted between the two cytokines and plasminogen activator inhibitor-1. CONCLUSIONS: In the patients with trauma, DIC is a predictor of ARDS, multiple organ dysfunction syndrome, and death. TNF-alpha and IL-1 beta might be one of the causes of DIC, while plasminogen activator inhibitor-1 may be one of the aggravating factors of ARDS and multiple organ dysfunction syndrome. Plasminogen activator inhibitor-1 is a good predictor of death for posttrauma DIC patients.

APACHE↗

PubMed1995

Soluble thrombomodulin increases in patients with disseminated intravascular coagulation and in those with multiple organ dysfunction syndrome after trauma: role of neutrophil elastase.

OBJECTIVE: Our goal was to investigate the role of soluble thrombomodulin (TM) and neutrophil elastase in patients with trauma. DESIGN: This study is a prospective case-control study. MATERIALS AND METHODS: Forty-seven trauma victims, 14 with disseminated intravascular coagulation (DIC), 5 with multiple organ dysfunction syndrome (MODS), and 28 control patients without DIC or MODS were the participants. Soluble TM and neutrophil elastase (elastase-alpha1-proteinase inhibitor complex) were measured on the day of the injury, and on the first, third, and fifth days after admission. The results of these measurements and demographic data were compared among the groups, and correlations between the soluble TM and the neutrophil elastase were examined. The DIC patients were classified into subgroups of survivors (n = 5) and nonsurvivors (n = 9), and the changes of the soluble TM between the subgroups were then studied. MEASUREMENTS AND MAIN RESULTS: A high incidence of DIC patients encountered MODS complications (12 of 14, 86%). The DIC patients had higher Injury Severity Scores (ISSs) than the other patients. The levels of soluble TM and neutrophil elastase significantly increased on the day of admission in the patients with DIC and also in those with MODS (p < 0.05 vs. control patients) and continued to show markedly high values until the fifth day of admission in the patients with DIC. In the DIC patients, the levels of soluble TM were higher in the nonsurvivors than in the survivors (p < 0.05 on the third and the fifth days of admission). In all patients, there was weak but statistically significant correlation between peak levels of soluble TM and ISS (r2 = 0.125, p < 0.025). Comparison of the levels of soluble TM and neutrophil elastase in the patients with DIC or MODS demonstrated an excellent correlation (r2 = 0.718 and r2 = 0.714, respectively). CONCLUSIONS: Soluble TM as a novel endothelial cell injury marker increases in patients with DIC and also in those with MODS after trauma. Neutrophil elastase may be involved in the pathogenesis of the injury. Soluble TM is a marker of the severity of injury and is a good predictor of MODS.

Adult↗

PubMed1994

Diagnostic and prognostic value of fibrinopeptides in patients with clinically suspected pulmonary embolism.

To determine the diagnostic and prognostic value of fibrinopeptides in patients with clinically suspected pulmonary embolism (PE), we made a pilot study in the Emergency Department with a general ICU. 32 patients with clinically suspected pulmonary embolism were the participants and 16 cases were diagnosed as PE-positive. After the diagnosis of PE, thrombolytic therapy with urokinase was administered, followed by heparin therapy. Plasma fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta 15-42) were measured before treatment and at 1, 2 and 6 days after treatment. In the PE-positive patients, the levels of both fibrinopeptides measured prior to the treatment were above the normal values, and were significantly higher than those of PE-negative patients. When the cutoff points of FPA and, FPB beta 15-42 were set at 15 ng/ml, 15 ng/ml respectively, both markers had a high sensitivity, a highly negative predictive value and a moderate specificity. Six of the PE-positive patients died. The FPB beta 15-42 levels were significantly lower in the survivors than those in the patients who died at 2 days (p = 0.0092) and 6 days (p = 0.0011). We can conclude that: 1) the fibrinopeptide measured in this study are useful for screening for PE; and 2) FPB beta 15-42 may possibly be useful as a method for predicting the clinical outcome of PE.

Biomarkers↗

PubMed1994

Attenuated contractile response of diabetic rat aorta to caffeine but not to noradrenaline in Ca(2+)-free medium.

The phasic contractions induced by noradrenaline and caffeine were compared in aortic rings from rats with 8-12 week streptozotocin-induced diabetes and age-matched control rats. In Ca(2+)-free medium, no difference was found in the magnitude of the contractile responses to 10 microM noradrenaline between control and diabetic aortas. The transient contraction induced by 20 mM caffeine was significantly diminished in diabetic aorta compared aorta. The results suggest that the ability of caffeine, but not of inositol 1,4,5-trisphosphate, to mobilize Ca2+ from intracellular stores is impaired in diabetic rat aorta.

Animals↗

PubMed1994

The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients.

A retrospective study was conducted on 53 patients who suffered severe trauma to determine the severity of intravascular hemolysis, the variations of renal function after trauma, and the effects of transfusion and haptoglobin therapy on these factors. Serum total haptoglobin, total hemoglobin, and urine free hemoglobin were measured 0, 1, 3, and 5 days after the trauma and renal tubular function was evaluated by the urinary N-acetyl-beta-D-glucosaminidase (NAG) index. Patients were divided into two groups depending on whether or not haptoglobin was given: group A (n = 34) did not receive haptoglobin, and group B (n = 19) was administered 4,421 +/- 245 U haptoglobin based on clinical indications. The total transfusion volumes were 3,477 +/- 594 ml and 10,146 +/- 1,794 ml, in groups A and B, respectively (P < 0.01). In group A, total haptoglobin was remarkably decreased to 69.4 +/- 11.6 mg/dl on day 0, but recovered to within the normal range on day 3, while the total hemoglobin was increased and the urine hemoglobin was positive in 61.8% of the patients. In group B, decreases in total haptoglobin and increases in total hemoglobin were more remarkable, and 84.2% had a positive urine hemoglobin. On day 5, groups A and B had NAG indices of 18.8 +/- 3.3 and 133.6 +/- 33.8 U/L/creatinine respectively (P < 0.01). These findings led us to conclude that trauma caused hemolysis and that the administration of 4,000 U haptoglobin did not improve either the severity of hemolysis or the deteriorated renal tubular function caused by massive transfusion.

Acetylglucosaminidase↗

PubMed1994

Histamine receptors mediating a positive inotropic effect in guinea pig and rabbit ventricular myocardium: distribution of the receptors and their possible intracellular coupling processes.

The difference in histamine receptor subtypes that are involved in the positive inotropic effect of histamine in guinea pig and rabbit ventricular myocardium was analytically characterized. In guinea pig papillary muscles, the positive inotropic effect of histamine was antagonized by cimetidine but not by mepyramine. The converse was true in rabbit papillary muscles. However, histamine evoked a positive inotropic effect through H1- and H2-receptors after blockade of H2- and H1-receptors in guinea pig and rabbit papillary muscles, respectively. Adenylate cyclase was significantly activated by histamine via H2-receptors in guinea pig but not in rabbit myocardial ventricular membranes. Accumulation of [3H]inositol monophosphate in ventricular strips prelabeled with myo-[3H]inositol was increased by histamine via H1-receptors to a similar extent in rabbits and guinea pigs. Radioligand binding experiments with [3H]mepyramine and [3H]tiotidine showed an increased number of H1-receptors and a decreased number of H2-receptors in guinea pig compared with rabbit ventricular myocardium. These results suggest that the positive inotropic effects of histamine are dominated by an H1-receptor-mediated effect in rabbits and by an H2-receptor-mediated one in guinea pig ventricular myocardium, and the positive inotropic effect manifested by one subtype apparently restricts the expression of the positive inotropic effect mediated by the other subtype. This species difference is not due to a difference in densities of the receptor subtypes, but may be partly related to a difference in the extents of coupling of H2-receptors to adenylate cyclase.

Adenylyl Cyclases↗

PubMed1994

[Pharmacological studies on alterations in myocardial beta-adrenoceptors and their intracellular signal transduction in experimental diabetic rats].

The present study was undertaken to determine abnormalities which are responsible for the diminished functional responsiveness to beta-adrenoceptor stimulation in experimental diabetic rats. Rats were given an intravenous injection of 45mg/kg streptozotocin and hearts were removed from 4 to 6 weeks later. The positive inotropic effects of isoproterenol, norepinephrine and epinephrine were markedly depressed in diabetic rat papillary muscles. Diabetic cardiac muscles also exhibited a reduced maximum contractile responses to forskolin, 3-isobutyl-1-methylxanthine and dibutylic cyclic AMP. The density of beta-adrenoceptors in membranes prepared from diabetic hearts was decreased by 40%, with uniform decreases in the beta 1- and beta 2-subtypes. The affinity of the receptor for the radioligand antagonist [125I]-iodocyanopindolol remained unchanged. Competition binding studies with isoproterenol did not reveal a difference in the fraction of beta-adrenoceptors with high-affinity binding between control and diabetic cardiac membranes, suggesting that interaction between beta-adrenoceptors and Gs may be preserved well in the diabetic state. All measures of adenylate cyclase activity showed that beta-adrenoceptor-dependent and Gs-dependent cyclic AMP productions are well maintained in membranes from diabetic hearts. Thus, these data suggest that the decreased positive inotropic response to beta-adrenoceptor stimulation in diabetic hearts is not attributable to changes in beta-adrenoceptor-Gs-adenylate cyclase system but rather may be due to an alteration in cellular function beyond the level of cAMP generation. To test this hypothesis, incorporation of [32P]-inorganic phosphate into phospholamban in sarcoplasmic reticulum was examined in Langendorff-perfused hearts. Isoproterenol (100nM) increased phosphorylation of phospholamban threefold in control hearts, but did not cause a significant change in the phosphorylation state in diabetic hearts. From these findings it is concluded that the decreased functional responses to cyclic AMP-increasing agents like beta-adrenoceptor agonists in diabetic hearts may be associated with impaired phosphorylation of cardiac regulatory phosphoproteins including phospholamban.

Adenylyl Cyclases↗

PubMed1994

[Increased fibrinolytic activity during cardiopulmonary bypass is caused by activated protein C system].

To examine the hypothesis that activated protein C system during cardiopulmonary bypass surgery may increase fibrinolytic activity during cardiopulmonary bypass, protein C activity, protein C antigen and thrombomodulin of sixteen patients undergoing elective cardiopulmonary bypass surgery were investigated after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of operation. Protein C activity decreased and thrombomodulin increased significantly after the cardiopulmonary bypass. There were no significant correlations of thrombomodulin with protein C activity and protein C antigen. In conclusion, we have demonstrated that protein C system is activated and circulating thrombomodulin appears in the systemic circulation during cardiopulmonary bypass surgery and this enhanced activation of protein C system is possibly related to the reported increase of fibrinolytic activity during cardiopulmonary bypass.

Anesthesia↗

PubMed1993

Altered cardiac adrenergic neurotransmission in streptozotocin-induced diabetic rats.

1. Functional alterations of the sympathetic neuroeffector junction of the left atria were studied in rats with streptozotocin-induced diabetes. 2. Eight to 12 weeks of diabetes resulted in a marked decrease in the positive inotropic response of left atria to electrical field stimulation (EFS). 3. The overflow of [3H]-noradrenaline from diabetic left atria caused by EFS was much less than that from control preparations. 4. The concentration-response curves showed no change in sensitivities of the left atria to exogenous noradrenaline and tyramine in diabetic rats. The maximum positive inotropic response to these agents were similar in diabetic and control animals. 5. The left atrial content of noradrenaline was not significantly changed in diabetic rats. The cocaine-sensitive uptake of [3H]-noradrenaline was also unaltered. 6. Atropine enhanced the positive inotropic response and [3H]-noradrenaline overflow induced by EFS in control left atria. Similarly, yohimbine caused an enhancement of EFS-evoked inotropic response in control atria. However, these effects of the antagonists were not observed in diabetic left atria. 7. It is concluded that the decrease in the positive inotropic response of the left atria to EFS in diabetic rats is caused by an impairment of noradrenaline release from the sympathetic nerve terminals through a calcium-dependent exocytotic mechanism. The present results also indicate that presynaptic alpha 2-adrenoceptors and muscarinic receptors that are linked to inhibition of the noradrenaline release during nerve stimulation may be functionally impaired in diabetic animals.

Animals↗

PubMed1992

Changes in coagulation and fibrinolytic activity associated with tracheal intubation.

This study was carried out to clarify the effect of tracheal intubation on the coagulation and fibrinolytic system. It was performed on 20 patients (ASA class 1-2) undergoing elective surgery. Before and after tracheal intubation, hemodynamics, ACTH, cortisol, catecholamines, and several coagulation and fibrinolytic factors were measured. Tracheal intubation was accompanied by significant increases in the blood pressure, heart rate, and norepinephrine level. No changes were observed in fibrinopetide A, fibrinopeptide B(Beta15-42), tissue plasminogen activator antigen, plasminogen, fibrinogen, and Alpha(2) plasmin inhibitor. Patients exposed to long intubation time (>20 seconds) were found to have a significantly higher level of fibrinopeptide A than patients with short tracheal intubation time (</=20 seconds) ( P < 0.05). It therefore can be concluded that the increase in norepinephrine and changes in the hemodynamics following tracheal intubation have no impact on the coagulation and fibrinolytic activity. Also, if the duration of intubation is prolonged, thrombin activity may be promoted.

Journal Article↗

PubMed1992

Posttrauma coagulation and fibrinolysis.

OBJECTIVE: To determine the effects of disseminated intravascular coagulation (DIC) and head injury on posttrauma coagulation and fibrinolysis. DESIGN: Case-control study. SETTING: General ICU (tertiary care center) in a city hospital serving a population of 150 million people. PATIENTS: Forty trauma victims: 15 with DIC; 25 without DIC. INTERVENTIONS: Measurement of six types of coagulation and fibrinolytic molecular markers (fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, D-dimer, tissue plasminogen activator antigen concentration, tissue plasminogen activator activity) immediately after trauma, 3 days later, and 6 days later. Anticoagulant treatment with gabexate mesilate at 1.45 +/- 0.06 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, and D-dimer showed high values immediately after trauma and exceeded normal activity for the first 6 days. When trauma was complicated with DIC, the molecular markers showed significantly higher values than those for non-DIC patients on all days. In the head-injured patients, such effect was not noted. Tissue plasminogen activator antigen concentration and tissue plasminogen activator activity were within a normal physiologic range of variation. By contrast, tissue plasminogen activator antigen concentration increased significantly after trauma in patients with DIC. When anticoagulant treatment was found effective, it caused a reduction in fibrinopeptide A. CONCLUSIONS: a) Fibrinolytic shut-down and its reactivation cannot be confirmed after trauma. b) Head injury does not lead to an increase in posttrauma coagulation or fibrinolytic activity. c) DIC enhances posttrauma coagulation and fibrinolytic activity and plasminogen activator inhibitor activity can be inferred in DIC patients. d) Increase in tissue plasminogen activator antigen concentration without tissue plasminogen activator activation may be a prognostic factor indicative of DIC and its chances of improvement, and fibrinopeptide A as an assessment criterion for the effectiveness of anticoagulant treatment.

Adult↗

PubMed1992

Selectivity of class I antiarrhythmic agents, disopyramide, pirmenol, and pentisomide for peripheral muscarinic M2 and M3 receptors.

The interactions of the class I antiarrhythmic agents, disopyramide, pirmenol, and pentisomide with peripheral muscarinic receptors were investigated by binding assay with [3H]N-methylscopolamine ([3H]NMS) as a ligand. All the agents inhibited the specific [3H]NMS binding to membrane preparations obtained from guinea pig submandibular gland (SG) and urinary bladder (UB) smooth muscle. The competition curves of these agents for [3H]NMS binding to SG membranes were monophasic, indicating competition with [3H]NMS at a single site. Comparison of results with those of our previous binding experiments using guinea pig left atrial (LA) membranes, showed that pirmenol had sevenfold lower affinity for glandular-type muscarinic receptors (M3) than for cardiac-type muscarinic receptors (M2). On the other hand, the dissociation constants (Ki) for disopyramide and pentisomide in SG were comparable to the high-affinity Ki values for these agents at M2 receptors. The competition curves of the three agents for [3H]NMS binding to UB membranes were biphasic and showed high- and low-affinity states of binding. The high- and low-affinity Ki values for pirmenol in UB were similar to its Ki values at M2 and M3 receptors obtained in LA and SG, respectively. The high-affinity Ki values for disopyramide and pentisomide were consistent with the respective Ki values determined in SG, whereas the low-affinity binding sites for these agents were presumably the result of their allosteric interactions with the receptors. All agents at higher concentrations slowed the dissociation of [3H]NMS elicited by an excess of atropine in both UB and SG, thus indicating allosteric interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗