Characterization and functional role of rapid- and slow-activating delayed rectifier K+ currents in atrioventricular node cells of guinea pigs.

The atrioventricular (AV) node is the only conduction pathway where electrical impulse can pass from atria to ventricles and exhibits spontaneous automaticity. This study examined the function of the rapid- and slow-activating delayed rectifier K+ currents (IKr and IKs) in the regulation of AV node automaticity. Isolated AV node cells from guinea pigs were current- and voltage-clamped to record the action potentials and the IKr and IKs current. The expression of IKr or IKs was confirmed in the AV node cells by immunocytochemistry, and the positive signals of both channels were localized mainly on the cell membrane. The basal spontaneous automaticity was equally reduced by E4031 and HMR-1556, selective blockers of IKr and IKs, respectively. The nonselective ß-adrenoceptor agonist isoproterenol markedly increased the firing rate of action potentials. In the presence of isoproterenol, the firing rate of action potentials was more effectively reduced by the IKs inhibitor HMR-1556 than by the IKr inhibitor E4031. Both E4031 and HMR-1556 prolonged the action potential duration and depolarized the maximum diastolic potential under basal and ß-adrenoceptor-stimulated conditions. IKr was not significantly influenced by ß-adrenoceptor stimulation, but IKs was concentration-dependently enhanced by isoproterenol (EC50: 15 nM), with a significant negative voltage shift in the channel activation. These findings suggest that both the IKr and IKs channels might exert similar effects on regulating the repolarization process of AV node action potentials under basal conditions; however, when the ß-adrenoceptor is activated, IKs modulation may become more important.

[Two Cases of Convulsive Seizures after Cardiac Surgery Suspiciously Caused by Tranexamic Acid Administration in Patients on Chronic Hemodialysis].

Tranexamic acid (TA), an antifibrinolytic agent, is commonly used in cardiac surgery with cardiopulmo- nary bypass to reduce bleeding. We report two cases of convulsive seizures after cardiac surgery with chronic kidney disease on hemodialysis. The two patients underwent aortic valve replacement, one for aortic valve regurgitation and another for aortic valve stenosis, with cardiopulmonary bypass uneventfully. A total dose of 8 g of TA was administered intravenously; 4 g during and 4 g after cardiopulmonary bypass. Both patients developed two episodes of gener- alized convulsive seizures post-operative day 1, which were suppressed by administration of diazepam intra- venously. The blood test, brain CT and electroenceph- alogram revealed no significant abnormalities. They were discharged without any neurological complica- tions. The high dose of TA was considered to have caused the seizures, since in previous reports the use of TA during surgery was associated with increased risk for postoperative seizures. It was demonstrated that approximately 40 to 70% of TA is excreted in the urine following intravenous administration. We posit that this might have led to excessive serum concen- tration of TA in our patients. Therefore, the dosage of TA should be decreased judiciously in patients with chronic kidney disease especially on hemodialysis to prevent postoperative seizures.

[Left ventricular migrating thrombus detected by intraoperative transesophageal echocardiography].

Transesophageal echocardiography (TEE) helps detecting intra-cavity thrombus size, mobility and fragility, which are of great importance in surgical removal of the thrombus. Thrombus characteristics may render surgical thrombectomy incomplete, raising the risk of catastrophic embolization. A 50-year-old man, suffering from congestive heart failure, developed a mobile thrombus in the left ventricle (LV). He was scheduled for a LV thrombectomy. TEE showed two thrombi on the apical side of the left ventricle, measuring 2.1 x 1.3 cm and 2.1 x 1.0 cm each. A surgical removal of these thrombi was performed under cardiopulmonary bypass (CPB). Just before separation from CPB, TEE detected a high echogenic mass in the LV Surgical re-explorations found residual thrombi, whose size, figure and echo signal strength resembled papillary muscles. This experience leads us to advocate repeated search for thrombi using TEE scans, in order to facilitate complete removal of thrombi prior to closing the ventriculotomy, and prior to weaning from CPB.

[Evaluation of the side effects of intravenous patient controlled analgesia after spine surgery].

BACKGROUND: We have adopted intrravenous patient controlled analgesia (IV-PCA) for spine surgery. We could not find reports about detailed examinations of the side effects of IV-PCA using morphine after spine surgery, so we investigated retrospectively side effects in cases using morphine IV-PCA. METHODS: Eighty-five patients underwent IV-PCA after spine surgery. The contents of PCA pump were morphine 20 mg (= 2 ml), droperidol 2 mg (= 0.8 ml), and saline 77 ml. We fixed continuous infusion at 2 ml x hr(-1), bolus infusion at 2 ml x hr(-1), and lockout time at 15 minutes. Respiration time, SpO2, blood pressure, pulse rate, nausea and vomiting, and VAS were monitored while IV-PCA was in use. When severe side effects were noticed, IV-PCA was discontinued by physician in charge. We judged discontinuation of IV-PCA as occurrence of severe side effects. RESULTS: IV-PCA was discontinued in seven patients. The causes of discontinuation were nausea and vomiting, hypotension, and bradycardia. Nausea and vomiting was the most common cause and found mostly in women. CONCLUSIONS: Because IV-PCA was discontinuated in 8.2% of patients, it was thought that its management depending on patients' personal state was necessary to utilize IV-PCA as a method of postoperative analgesia.

A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest.

DNA polymerase eta (Poleta) is responsible for efficient translesion synthesis (TLS) past cis-syn cyclobutane thymine dimers (TT dimers), the major DNA lesions induced by UV irradiation. Loss of human Poleta leads to xeroderma pigmentosum variant syndrome, clearly indicating that Poleta plays a vital role in preventing skin cancer caused by exposure to sunlight. To further examine Poleta functions and the mechanisms that regulate this important protein, Poleta complexes were purified from HeLa cells over-expressing epitope-tagged Poleta, and polypeptides associated with Poleta, including Rad18, Rad6 and Rev1, were identified by a combination of mass spectrometry and Western blot analysis. The chromatin-bound fractions of cells subjected to UV irradiation, S phase synchronization, or S phase arrest were specifically enriched in such complexes. These results suggest that arrested replication forks strengthen interactions among Poleta, Rad18/Rad6 and Rev1, consistent with the requirement for effective TLS by Poleta at sites of DNA lesions.