The Antiarrhythmic Action of the Na+/Ca2+ Exchanger Inhibitor SEA0400 on Drug-Induced Long QT Syndrome Depends on the Severity of Proarrhythmic Conditions in Anesthetized Atrioventricular Block Rabbits.

To clarify the pharmacological properties of the Na+/Ca2+ exchanger (NCX) inhibitor SEA0400 as an antiarrhythmic agent, we assessed its effects on rapid component of delayed rectifier K+ current (IKr) blocker-induced torsade de pointes (TdP) in isoflurane-anesthetized rabbits. Atrioventricular block was induced in rabbits using a catheter ablation technique, and the monophasic action potential (MAP) of the right ventricle was measured under electrical pacing at 60 beats/min. In non-treated control animals, intravenous administration of low-dose (0.3 mg/kg) or high-dose nifekalant (3 mg/kg) prolonged the MAP duration (MAP90) by 113 ± 11 ms (n = 5) and 237 ± 39 ms (n = 5), respectively, where TdP was induced in 1/5 animals treated with a low dose and in 3/5 animals treated with a high dose of nifekalant. In SEA0400-treated animals, low- and high-dose nifekalant prolonged the MAP90 by 65 ± 13 ms (n = 5) and 230 ± 20 ms (n = 5), respectively. No TdP was induced by the low dose but 1/5 animals treated with a high dose of nifekalant developed TdP. In verapamil-treated animals, low-dose and high-dose nifekalant prolonged MAP90 by 50 ± 12 ms (n = 5) and 147 ± 30 ms (n = 5), respectively, without inducing TdP. These results suggest that SEA0400 has the potential to inhibit low-dose nifekalant-induced TdP by suppressing the MAP-prolonging action of nifekalant, whereas the drug inhibited high-dose nifekalant-induced TdP without affecting the MAP-prolonging action of nifekalant. This may reveal that, in contrast to verapamil, the antiarrhythmic effects of SEA0400 on IKr blocker-induced TdP may be multifaceted, depending on the severity of the proarrhythmogenic conditions present.

[A Case Report of Robotic Assisted Laparoscopic Low Anterior Resection in a Patient with Rectal Cancer and Polysplenia Syndrome].

Polysplenia syndrome is a rare congenital disease characterized by variable thoracic and abdominal anomalies. A man in his 70s was diagnosed with rectal cancer by close exploration for fecal occult blood. A barium enema revealed a type 1 rectal tumor andwith non-rotation of intestine. CT revealed multiple abnormalities: a polyspleen, preduodenal portal vein, congenital absence of the pancreatic tail, bilateral superior vena cava, andbilateral bilobedlung. Basedon these findings, the patient was diagnosedas having rectal cancer with polysplenia syndrome andtreatedwith robotic assistedlaparoscopic low anterior resection. At operation, the whole colon was located in the left side of the abdominal cavity. The whole colon adhered with each other. The ileocecum adheredto the front of the aorta andthe right iliac artery. In the pelvis, anatomical abnormality was not detectedandrectal mobilization andresection was performedas usual. The patient hadno signs of recurrence of the rectal cancer. This is the first case presentation of laparoscopic low anterior resection in a patient with rectal cancer and polysplenia syndrome.

Relationship between phosphodiesterase inhibition induced by several Kampo medicines and smooth muscle relaxation of gastrointestinal tract tissues of rats.

Given a lack of information, we assessed the effects of Kampo medicines: Dai-saiko-to, Tsu-do-san, San'o-shashin-to, and Sairei-to, which have been used for various gastrointestinal diseases, on the phosphodiesterase activity and smooth muscle tone of the gastrointestinal tract. Clinically relevant concentrations of each Kampo extract (0.1 - 1 mg/ml) decreased the phosphodiesterase activity as well as smooth muscle tone. The extent of phosphodiesterase inhibition as well as smooth muscle relaxation by these Kampo extracts was prominent for the lower gastrointestinal tract. Also, there was a good correlation between the extents of drug-induced phosphodiesterase inhibition and smooth muscle relaxation, indicating the presence of their causal link. These results may partially provide the basis for understanding the mechanism of the clinical utility of Kampo extracts in gastrointestinal tract diseases.