The effect of thromboxane synthetase inhibition on cardiopulmonary function during endotoxemia in sheep

The early pulmonary hypertension seen with endotoxin (lipopolysaccharide) has been reported as resulting from the release of thromboxane A2. We studied the cardiopulmonary response to endotoxin in sheep with and without treatment with a thromboxane synthetase inhibitor, OKY-046. The animals were implanted with instruments for crystallographic dimension analysis of the left ventricle and measurement of left ventricular, aortic, left atrial, and pulmonary arterial pressures and cardiac index. Thirteen sheep received 1.0 micrograms/kg of Escherichia coli endotoxin with (n = 6) and without (n = 7) OKY-046 (10 mg/kg bolus, then 10 micrograms/kg/min). OKY-046 prevented the increase in pulmonary arterial pressure and decrease in cardiac index usually seen during the early phase of endotoxemia. Between 8 and 12 hours after the administration of endotoxin, cardiac index increased from 6.4 +/- 0.8 to 8.4 +/- 0.8 L/min/m2. Concomitantly, the end-systolic pressure/diameter relationship (a sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7 mm Hg/mm. Another index of the left ventricular contractility, the maximum rate of pressure rise was also reduced. OKY-046 prevented decreases in end-systolic pressure/diameter relationship and maximum rate of pressure rise.     

Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections]

Sputum penetration of levofloxacin (LVFX) was evaluated after a single oral dose of 100 mg or 200 mg to 4 patients with copious purulent sputa. The sputum concentration of LVFX reached maximum levels of 1.27 and 4.36 micrograms/ml at 4 hours, and still remained at concentrations of 0.32 and 1.68 micrograms/ml at 8 hours after administration of 100 mg and 200 mg, respectively. The AUC ratio of sputum/serum was 0.9-1.0, indicating good sputum penetration of LVFX in these patients. The clinical efficacy and the safety of LVFX were also evaluated in a total of 13 patients with respiratory tract infections associated with bronchiectasis, diffuse panbronchiolitis, etc. LVFX was administered orally at a daily dose of 200 mg once a day, 100 mg t.i.d. or 200 mg t.i.d. for 7-28 days (mean 14.7 days). The clinical response to the drug was rated as excellent in 1 case, good in 5, fair in 3, and poor in 2 cases in 11 evaluable cases, thus the efficacy rate was 54.5%. All the 3 strains of Haemophilus influenzae were eradicated. Of the 3 strains of Pseudomonas aeruginosa, eradication, decrease, and unchange was observed for 1 strain each. One strain of Streptococcus pneumoniae remained unchanged. No adverse reaction was observed except for 1 case with slight and temporary increase of eosinophils. The above results suggested that LVFX would be clinically useful in the treatment of chronic lower respiratory tract infections.     

Localization of calcium-accumulating structures in the anterior byssal retractor muscle of Mytilus edulis and their role in the regulation of active and catch contractions.

1. The localization of Ca-accumulating structures in the anterior byssal retractor muscle (ABRM) of Mytilus edulis and their role in the contraction-relaxation cycle were studied by fixing the ABRM at rest or during various phases of mechanical activity with a 1% osmium tetroxide solution containing 2% potassium pyroantimonate. 2. In the resting ABRM, electron-opaque pyroantimonate precipitate was observed at the inner surface of the plasma membrane, the vesicles and the mitochondria. 3. Electron X-ray microanalysis showed the presence of Ca in the precipitate, indicating that the precipitate provides a valid measure for Ca localization. 4. In the ABRM fixed at the peak of mechanical response to the Ca-removal or to acetylcholine, the precipitate was found to be diffusely distributed in the myoplasm in the form of a number of particles. At the completion of spontaneous relaxation, the precipitate was again seen at the inner surface of the plasma membrane. 5. During the catch state, the precipitate was found to be re-accumulated in the peripheral structures with a corresponding decrease of the precipitate in the myoplasm. 6. These results not only provide evidence for the involvement of the Ca-accumulating structures in the contraction-relaxation cycle in the ABRM, but also suggest that the transition from active to catch contractions is related to a decrease in myoplasmic free Ca ion concentration.     

An experimental study of determining the appropriate frequency of radiofrequency catheter ablation in vitro and in vivo for ventricular tachycardias]

The purpose of this study was to examine the appropriate frequency of radiofrequency catheter ablation (RFA) for ventricular tachycardia. Radiofrequency energy generated by a device in which the frequency could be changed, was delivered from an electrode catheter with an electrode tip-width of 4 mm. RFA was performed for 10 seconds with 20W (50V x 0.4A) using 7 different frequencies from 10 to 500 kHz on ventricular myocardium in vitro and in anesthetized dogs. The ablated lesion was significantly larger with RFA of 200-300 kHz in both surface area and depth (p less than 0.05). The appearance of ventricular arrhythmia during RFA increased as the frequency decreased, and one dog applied with RFA of 100 kHz had spontaneous ventricular fibrillation resulting in death. All dogs with frequency less than 100 kHz had a muscle cramp during RFA. We conclude that appropriate frequency seems to be 200-300 kHz to obtain a large ablated lesion, and a frequency higher than 300 kHz seems suitable to avoid arrhythmia. We also conclude that a frequency under 100 kHz should not be used.     

Studies on the erythrocyte membrane skeleton in a patient with chorea-acanthocytosis--theoretical speculation on the mechanism of neurological involvement]

Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes In Plasma Levels of Nitric Oxide Derivative During Low-Density Lipoprotein Apheresis

Abstract: The negative charges of dextran-sulfate (DS) used for low-density lipoprotein (LDL) apheresis activates the intrinsic coagulation pathway, in which plasma kallikrein acts on high-molecular-weight kininogen (HMWK) to produce large amounts of bradykinin. This study was undertaken to see whether bradykinin generated during DS LDL apheresis has some physiologic effects in vivo. The plasma levels of bradykinin and nitric oxide derivatives (NOx) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity, this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the marked increase in bradykinin levels (before apheresis, 18 ± 3 (mean ± SE, n = 5) pg/ml; after apheresis 470 ± 140, p < 0.01) was associated with the increase in NOx (before apheresis 50 ± 11 pg/ml; after apheresis 66 ± 15). Interestingly, these changes in bradykinin and NOx levels were suppressed during apheresis using NM. The changes in plasma NOx levels were negatively correlated with those in blood pressures. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects by means of activation of endothelium-derived relaxant factor (EDRF). Our results support the view that bradykinin produced during DS LDL apheresis has physiologic significance.—