PubMed Health⌕ Search

Biomedical subjects

S Gando

Publications and source records attributed to S Gando.

At least 73 records · Page 4Linked to original sources

Characterization of histamine receptors modulating inotropic and biochemical activities in rabbit left atria.

The experiments were performed to identify histamine H1- and H2-receptors in rabbit left atrium and to characterize the pharmacological properties mediated by the respective subtypes of histamine receptors. High-affinity saturable binding to the left atrial membranes was obtained for [3H]mepyramine, yielding a maximum binding capacity (Bmax) of 96 fmol/mg of protein and an equilibrium dissociation constant (KD) of 3.8 nM and also for [3H]tiotidine, yielding a Bmax of 126 fmol/mg of protein and a KD of 14.7 nM. In isolated left atrium, histamine produced a concentration-dependent positive inotropic effect, an effect which was competitively antagonized by cimetidine but not altered by chlorpheniramine. Schild analysis showed that the pA2 value for cimetidine was 6.55 and the slope was not significantly different from unity. An excellent correlation was found between the increase in force of contraction and cyclic AMP in the presence of histamine, suggesting that the positive inotropic effect of histamine in rabbit left atrium is dependent on an increased level of intracellular cyclic AMP through stimulation of histamine H2-receptors. Histamine also produced concentration-dependent stimulation of phosphoinositide hydrolysis as measured by [3H]inositol monophosphate accumulation. The phosphoinositide response to histamine was blocked by chlorpheniramine and mepyramine but not by cimetidine. The data indicate that histamine H1-receptors, in addition to histamine H2-receptors, are present in the rabbit left atrium. Although this tissue lacks an inotropic response to histamine H1-receptor stimulation, the histamine H1-receptors interact with histamine to mediate the stimulation of phosphoinositide hydrolysis.

Animals↗

Identification and characterization of histamine H1- and H2-receptors in guinea-pig left atrial membranes by [3H]-mepyramine and [3H]-tiotidine binding.

1. Histamine receptors in the membranes prepared from guinea-pig left atria were characterized with [3H]-mepyramine and [3H]-tiotidine binding. 2. The binding of the H1-antagonist, [3H]-mepyramine, was saturable and of high affinity with a maximum binding capacity of 307 +/- 27 fmol mg-1 protein (n = 14) and with an equilibrium dissociation constant (KD) of 1.5 +/- 0.2 nM (n = 14). The binding was rapid and readily reversible. 3. The competition curve for [3H]-mepyramine binding by histamine was biphasic and revealed high and low affinity states of binding. The addition of 5'-guanylylimidodiphosphate (GppNHp) (100 microM) converted this heterogeneous binding into homogeneous binding of low affinity. 4. The competition curves of H1-antagonists with [3H]-mepyramine had Hill coefficients not significantly different from unity, consistent with competition with [3H]-mepyramine at a single site. GppNHp did not shift the competition curves. 5. Dissociation constants for H1-antagonists determined from inhibition of [3H]-mepyramine binding correlated well with the constants derived from inhibition of the positive inotropic response of guinea-pig left atria to histamine. 6. The H2-antagonist, [3H]-tiotidine, labelled an apparently homogeneous population of recognition sites with a maximum binding capacity of 41 +/- 8 fmol mg-1 protein (n = 6) and a KD of 10.8 +/- 1.2 nM (n = 6). 7. Although histamine competed for [3H]-tiotidine binding in a concentration-dependent manner, the curve was monophasic and was not shifted by GppNHp. 8. It is concluded that both H1- and H2-receptors exist in guinea-pig left atria. H1-receptors probably couple to intracellular effector(s) through a guanine nucleotide-dependent transducing mechanism. On the other hand, H2-receptors seem unlikely to be linked to guanine nucleotide regulatory proteins in guineapig left atria, which may explain the failure of histamine to cause an increase in cyclic AMP in spite of the presence of H2-receptors.

Animals↗

[Correlations among FPB beta 15-42, PAC and D-dimer].

We measured FPB beta 15-42, and alpha 2 plasmin inhibitor-plasmin-complex (PAC), which are direct indexes of plasmin activity, as well as D-dimer in 204 samples from patients with subarachnoid hemorrhage, trauma, and the patients during cardiopulmonary bypass. In all patients, these molecular markers increased due to secondary fibrinolysis; these increases were significantly higher in DIC patients. There were positive correlations among the molecular markers. The correlation coefficient for FPB beta 15-42 and D-dimer was significantly higher than that for PAC and D-dimer in the DIC patients. In conclusion, it might be better to measure both FPB beta 15-42 and PAC as indexes of plasmin activity in DIC patients, because of the significant difference between the correlation coefficient for PAC and D-dimer, and that for FPB beta 15-42 and D-dimer.

Adult↗

Binding profiles of class I antiarrhythmic agents to cardiac muscarinic receptors: competitive and allosteric interactions with the receptors and their pharmacological significance.

The binding profiles of the class I antiarrhythmic agents disopyramide, pirmenol and pentisomide (CM7857) to cardiac muscarinic receptors were characterized by the binding assay using [3H]-N-methyl scopolamine ([3H]NMS) as a ligand and their anti-muscarinic actions were investigated functionally in left atrial preparations. All the agents displaced the specific binding of 200 pM [3H]NMS from guinea pig left atrial membranes. Computer-assisted analysis indicated that pirmenol interacted with a single class of binding sites, but the displacement curves of disopyramide and pentisomide were shallow and best fitted to a two-site model. When the concentration of [3H]NMS was increased to 1 nM, the displacement curve of pirmenol was best fitted to a two-site model. In higher concentrations, these agents inhibited the dissociation of [3H]NMS initiated by 1 microM atropine in a concentration-dependent manner, thus revealing allosteric interactions. Two enantiomers of pirmenol possessed qualitatively the same binding properties as the racemate. In guinea pig left atria, disopyramide, pirmenol and pentisomide shifted the concentration-response curves for the negative inotropic effect of carbachol in a parallel manner. The slopes of Schild plot were not significantly different from unity, indicating that they act as a competitive antagonist of cardiac muscarinic receptors. Excellent correlation between the high affinity pKi values and the pA2 values was established for the antiarrhythmic agents. These findings suggest that disopyramide, pirmenol and pentisomide all interact with cardiac muscarinic receptors in both a competitive fashion and an allosteric one. The dual mode of the interaction with cardiac muscarinic receptors seems to be independent of their chiralities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of serum ionized calcium in arterial and mixed venous blood during CPR.

Changes in the actual ionized calcium level (aCa2+) of serum in arterial and mixed venous blood during CPR were investigated in 22 patients with intrinsic cardiopulmonary arrest. Measurements were carried out at an average of 5.4 +/- 0.6 minutes (group 1) and 30 minutes (group 2) after the beginning of CPR, using simultaneously taken blood samples. The aCa2+ of groups 1 and 2 revealed no difference between arterial and mixed venous bloods. As CPR proceeded, the aCa2+ of both bloods diminished, and group 2 had a significantly lower value than did group 1 (arterial blood: 2.36 +/- 0.04 mEq/L vs 2.09 +/- 0.09 mEq/L, P less than .01; mixed venous blood: 2.37 +/- 0.05 mEq/L vs 2.13 +/- 0.06 mEq/L, P less than .001). Conversely, pH values were significantly higher for arterial blood rather than for mixed venous blood, but there was no significant change in pH between groups 1 and 2 (arterial blood, 7.11 +/- 0.05 vs 7.14 +/- 0.04; mixed venous blood, 6.93 +/- 0.04 vs 6.98 +/- 0.03). Furthermore, an analysis of the aCa2+ serum level measurements was carried out in relation to survivors and nonsurvivors and to the presence or absence of a witness at the time of the cardiac arrest. In all groups, there was no difference in aCa2+ between arterial and mixed venous blood. As CPR proceeded, however, the aCa2+ showed a significant decrease in all groups. This decrease was accompanied by a pH increase in arterial blood of patients with a witnessed cardiac arrest and in mixed venous and arterial blood of survivors.

Aged↗

[Variation in wound healing factors in trauma patients].

Serial changes of activated factor XIII (XIIIa), alpha 2 Plasmin inhibitor (alpha 2PI) and fibronectin (FN), which have important role in wound healing and host defence mechanism, were studied in 27 trauma patients. We obtained the results as follows. 1) The alpha 2PI and the FN decreased in proportion to injury severity score (ISS) immediately after trauma and they increased statistically significantly on the second or the third hospital day. On the other hand the XIIIa showed no statistically significant changes after trauma. 2) Emergency operations performed on the first hospital day had no influence on the variations of the XIIIa, the alpha 2PI and the FN. 3) The patients with disseminated intravascular coagulation (DIC) showed statistically marked decrease of the XIIIa, the alpha 2PI, and the FN on admission and the first hospital day compared with those patients without DIC. On the second hospital day, there was no difference of these factors between the DIC patients and the patients without DIC, but on the following day the alpha 2PI and the FN decreased again. In conclusion, the alpha 2PI and the FN decrease in proportion to ISS but XIIIa shows no significant changes after trauma. Emergency operations have no influence on the variations of these factors but with complicating DIC, all of these factors decrease significantly.

Adult↗

[An analysis of DIC in patients with multiple organ failure--variations of the molecular makers and its clinical usefulness].

We studied blood coagulation and fibrinolysis in 18 DIC patients with multiple organ failure. Blood was collected three times (1st, 3rd, 6th hospital days) from an indwelling arterial line, and FPA, FPB beta 15-42, alpha 2PI-P1-C, D-dimer, t-PA; Ag, and t-PA activity were measured. 1) Continuous FOY infusion (1.40 +/- 0.07 mg/kg/H) resulted in a statistically significant fall of FPA levels, which however, was still above normal. The FPA levels of the patients whose DIC score was not improved or who had massive hematomas were statistically higher than the patients whose DIC score was improved or without hematomas. 2) FPB beta 15-42, alpha 2PI-Pl-C, and D-dimer remained at consistently high levels following onset of the DIC. A significant positive correlations were seen between these indices; between the FPA and FPB beta 15-42, alpha 2PI-Pl-C. 3) The levels of alpha 2PI-Pl-C were found to be higher in the patients with hematomas than those without hematomas. 4) T-PA; Ag level remained at consistently high during all hospital day. On the other hand, t-PA activity level did not change significantly. There was dissociation between the t-PA; Ag and the t-PA activity. 5) The patients whose DIC score were not improved on the 6th hospital day had higher levels of t-PA; Ag than the patients whose DIC score were improved, but there were no differences in the number of the ischemic organs between these patients. In conclusion, regardless of the continuous FOY infusion some patients revealed the continuous production of thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Increased fibrinolytic activity during surgery with cardiopulmonary bypass].

We studied blood coagulation and fibrinolysis in 19 patients during surgery with cardiopulmonary bypass (CPB). CPB was performed with a rotating pump and a membrane oxygenator. Heparinization was achieved with heparin 3 mg.kg-1 and the ACT value was kept above 400 seconds throughout the CPB. Heparin was neutralized by protamine at a ratio of 1:1-1.5 of the total amount of heparin. Blood was collected four times from an indwelling arterial line. We obtained the first sample immediately after induction of anesthesia, the second sample before heparinization, the third sample before protamine administration, and the fourth sample at the end of the operation. FPA, FPB beta 15-42, alpha 2PI-Pl-C, D-dimer, and the t-PA activity were measured. A statistically significant elevation of FPA was observed during the operation. FPB beta 15-42, alpha 2PI-Pl-C, and the D-dimer rose significantly immediately after the beginning of the CPB and these elevations continued until the end of the operation. The t-PA activity was elevated significantly only during the CPB. In conclusion, the t-PA is released from the endothelial cells during CPB by some undetermined mechanism (primary fibrinolysis). Then, plasmin is generated by the t-PA and this dissolves the fibrin clots formed by thrombin before the beginning of the CPB (secondary fibrinolysis). Enhanced fibrinolytic activity before and after the CPB is physiological secondary fibrinolysis.

Cardiopulmonary Bypass↗

[Wound healing, blood coagulation and fibrinolysis during operations involving gastric cancer surgery].

Serial changes of FPA, FPB beta 15-42, FN, XIIIa, and alpha 2PI were investigated for the study on wound healing, blood coagulation, and fibrinolysis during gastric cancer surgery. For a control, we compared the preoperative values with the postoperative ones. These results also were compared with the values in healthy volunteers and in patients with cholelithiasis or myoma uteri. Our findings were as follows; 1) Compared with the control values, a statistically significant elevation of FPA, FPB beta 15-42 and FPA/FPB beta 15-42 ratios in patients with gastric cancer was noticed after operation. 2) Compared with the control values, a statistically marked decrease of FN, XIIIa and alpha 2PI in patients with gastric cancer was observed after operation. 3) The preoperative FPA and FPB beta 15-42 levels of gastric cancer patients were appreciably greater than those of normal healthy volunteers. Compared with patients with cholelithiasis or myoma uteri, however, the only preoperative FPA of gastric cancer patients showed significantly high levels. 4) FN and alpha 2PI revealed a notable positive correlation. These results suggest (1) increase of coagulation activity (thrombin formation) in gastric cancer patients; (2) increase of intravascular coagulation and fibrinolytic activity (thrombin and plasmin formation) during gastric cancer surgery; and, (3) depression of FN, XIIIa and alpha 2PI during surgery was due to sequestration at the site of tissue injury.

Adult↗

Variation in serum ionized calcium on cardiopulmonary resuscitation.

Changes in serum ionized calcium (Ca(++)) levels during cardiopulmonary resuscitation (CPR) and before and after CaCl(2) administration have been examined and investigated in 30 patients with cardiopulmonary arrest on arrival (dead on arrival patients) when a significant negative correlation was found to exist between the transportation time and aCa(++), as the aCa(++) level decreased with an increase in the transportation time. Upon arrival, the pH had fallen due to acidosis so that aCa(++) and cCa(++) levels were virtually normal. After admission, the pH rose as a result of CPR, resulting in a significant drop in both Ca(++) levels, so that in most cases resuscitation was not possible. Those successfully resuscitated took over 60 min to return to normal Ca(++) levels. Administration of approximately 6.6 mg/kg of CaCl(2) led to significant increases in aCa(++) and cCa(++) to essentially normal levels, even with some patients recording extremely elevated Ca levels, even with some patients recording extremely elevated Ca levels. However, the success rate of resuscitation was not found to show any significant difference according to whether CaCl(2) had or had not been administrated.Thus, it is felt necessary to re-examine the use of calcium chloride on CPR.

Journal Article↗

Can blood gas analysis indicate when mechanical ventilation should start in patients with acute myocardial infarction?

Arterial blood gas analysis of 69 patients with acute myocardial infarction were evaluated to provide a basis for respiratory care. Patients were divided into two groups: group A which received oxygen therapy only (n = 38) and group B which received oxygen therapy with mechanical ventilation (n = 31). The patients in group B were further divided into surviving cases (n = 14) and fatal cases (n = 17). On admission patients assigned to group B had lower PaO2 values than those placed in group A. In group B, there was no difference in the P/F value before mechanical ventilation of the surviving and the fatal cases, but the survivors demonstrated an improvement of the P/F value and an increase in cardiac index after mechanical ventilation. It may be reasonable to assume that a P/F value of less than 250 serves as an indicator for the initiation of mechanical ventilation. An increase in the P/F value after mechanical ventilation seems to be a valuable index to estimate prognosis in respiratory failure.

Blood Gas Analysis↗

[Non-clostridial gas-producing brain abscess in a brain death patient--report of a case].

A 46 year old female was admitted to our emergency room because of cardiopulmonary arrest by hanging. After ten minutes cardiopulmonary resuscitation, she was resuscitated but her consciousness did'nt recover. CT-scans on the day of admission showed no abnormalities but on the second hospital day it showed symmetrical low density areas within the basal ganglia, the thalamus, the hippocampus, and the occipital lobe. There were marked enhanced effect in cerebral sulci due to cytotoxic edema of hypoxic encephalopathy. She was comatose for a week, her pupils were dilated, light reflex and other brain stem reflex were absent. CT-scans on the sixth hospital day showed marked brain swelling with disappearance of the ventricular systems (so called brain tamponade). Brain death was confirmed on the basis of Japanese Criteria on the seventh and tenth day of admission. She had been suffering from pneumonia and urinary tract infection with an elevation of temperature since the fourth hospital day. We detected Enterobacter Cloacae (E. Cloacae), Klebsiella Oxytoca from the cultures of sputum and urine. On the tenth hospital day her temperature was running up to 39.4 degrees C and blood count revealed a peripheral blood leucocytosis of 40,300/mm3 with a shift to the left. E. Cloacae was also detected from the cultures of blood. Skull roentgenogram showed multiple gas collections in the ventricular systems. CT-scans on the fourteenth hospital day showed multiple gas-containing brain abscess. The etiology of this infection was considered due to septicemia of E. Cloacae. She died from acute renal failure on the fifteenth hospital day. Consent for autopsy was not accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Abscess↗

Phosphodiesterase III inhibitor olprinone chlorate is not significantly removed by continuous venovenous hemodiafiltration.

The study objective was to determine whether a phosphodiesterase III inhibitor, olprinone chlorate, is effectively removed by continuous venovenous hemodiafiltration (CVVHDF) in a patient with cardiac and renal failure. The patient was a 73 year old man who had undergone coronary artery bypass grafting for ischemic heart disease and who developed cardiac and renal failure postoperatively. A 0.2 microg/kg per minute dosage of olprinone chlorate was administered intravenously for 120 minutes while the patient was treated with CVVHDF. Samples from the arterial and venous blood catheters and those from the ultradiafiltrate for 12 hours were collected to calculate pharmacokinetic parameters and clearance of hemodiafiltration. The calculated parameters were as follows: half-life of elimination phase: 4.96 hours; total clearance 3.40 ml/min per kg. The clearance of CVVHDF was 0.33 ml/min per kg. The olprinone chlorate clearance of CVVHDF approximates only 10% of total clearance in this case. CVVHDF may not produce significant reduction in the serum olprinone chlorate level. It is recommended that the infusion dosage of olprinone chlorate should be reduced when given to patients with renal failure even if treated with CVVHDF.

Aged↗

Predictors of mortality in patients treated with continuous hemodiafiltration for acute renal failure in an intensive care setting.

We performed this study to identify predictors of mortality in critically ill patients treated with continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure in an intensive care setting. It was an uncontrolled, observational study that took place in a general intensive care unit in a university hospital. Forty-one patients undergoing CVVHDF for acute renal failure in a consecutive sample of 1,018 ICU treatments were studied. The underlying disease included 25 postsurgical cases and 16 medical cases. Between survivors (n = 23) and nonsurvivors (n = 18), the following factors were assessed: demographic data; the number and type of failed organs; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; urine production; pH; base excess; serum creatinine levels; bilirubin levels; lactate levels; platelet counts; and hemodynamic variables, including cardiac index and central venous pressure. On univariate analyses, the number of failed organs (p < 0.01), presence of hepatic failure (p < 0.01), APACHE II scores (p < 0.01), pH (p < 0.01), base excess (p < 0.001), average urinary production before the initiation of CVVHDF (p < 0.05), and serum bilirubin (p < 0.01) and lactate levels (p < 0.001) were significantly different. Multiple regression analysis identified serum bilirubin (p < 0.01) and lactate levels (p < 0.01) as the predictors of hospital mortality. Presence of hepatic failure was also predictive of hospital mortality (p < 0.01) in the analysis of the type of organ failure. The cut-off value set at bilirubin levels > 10 mg/dl or arterial lactate levels > 3.5 mmol/L provided 83.3% sensitivity and 90.9% specificity in the prediction of hospital death. The crucial factors in predicting outcome of critically ill patients undergoing CVVHDF for renal failure are elevated serum bilirubin and lactate levels at the onset of CVVHDF. Presence of hepatic failure, defined as both jaundice and coagulopathy, may also worsen outcome of critically ill patients undergoing CVVHDF for renal failure. The cut-off value set at bilirubin levels > 10 mg/dl or arterial lactate levels > 3.5 mmol/L may serve as beneficial predictors of hospital mortality.

APACHE↗