心筋異方向性伝導と心室性不整脈発生機序に関する高密度マッピング法を用いた研究

金沢大学医学部附属病院【目的】心筋組織は心筋線維の配列方向によって興奮伝導速度が異なる異方向性伝導特性を有し,摘出心筋を用いた検討などから,心筋構築の異方向性がリエントリ-性不整脈発生機構に関与する可能性が指摘されているが,未だ十分に解明されてはいない.本研究では,イヌ生体拍動心に高密度マッピング法を用いて急性心筋虚血時における心筋異方向性伝導と心室性不整脈発生の関係を解明することを目的とした.【方法】雑種成熟イヌ8頭(8〜12kg)をpentobarbitalで麻酔後,人工呼吸下で開胸し,心膜を切開して心臓を露出し,左冠状動脈前下行枝(LAD)潅流領域にマッピング電極を留置した.マッピングには極間1mmの双極金球電極96対を1.5mm間隔に8列×12行に配列し,中央に記録用電極とは別に刺激用双極電極を1対配したマット電極を用いた.Base lineの記録終了後LADを近位部で結紮し,経時的に中央刺激電極で基本刺激周期300msの刺激を行い興奮伝播過程を記録した.興奮伝播様式の記録解析にはHPM-7100(フクダ電子社)を用いた.【結果】Base lineにおける心表面心筋線維の長軸方向興奮伝播速度(以下θL)は,θL=0.705±0.067m/s,短軸方向興奮伝播速度(以下θT)は,θT=0.344±0.057m/sであった.LAD結紮5〜10分後には,θL=0.472±0.123m/s,θT=0.255±0.038m/sといずれも有意に低下した.結紮20〜30分後θL=0.561±0.128m/sと長軸方向の興奮伝播速度が一時改善したが,結紮40〜50分後には再び興奮伝播速度の低下が認められた(θL=0.441±0.112m/s,θT=0.253±0.073m/s).【総括】イヌ急性心筋虚血モデルにおいて,心表面異方向性伝導の経時的な変化率に差がみられ,この過程が急性心筋虚血時の不整脈発生機序と関連する可能性が示唆された.研究課題/領域番号:07770496, 研究期間(年度):1995出典：研究課題「心筋異方向性伝導と心室性不整脈発生機序に関する高密度マッピング法を用いた研究」課題番号07770496（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-07770496/）を加工して作

非持続型心室頻拍の興奮伝播様式および心室細動移行様式に関する実用的検討: 心表面マッピング法および3次元マッピング法を用いた検討

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第962号, 学位授与年月日：平成2年9月30日,学位授与年：199

γ-Tocopherol Accelerated Sodium Excretion in a Dose-Dependent Manner in Rats with a High Sodium Intake

We have previously reported that γ-tocopherol (γ-Toc) displays a natriuretic potency in rats fed a NaCl diet and administered 20 mg γ-Toc. In this study, we investigated whether γ-Toc has natriuretic potency at a dose lower or higher than 20 mg in rats given a NaCl diet. Male rats were fed a control diet or a NaCl diet and administered either placebo or 10, 20 or 40 mg of γ-Toc. The rat urine was collected for 24 hours (divided into 6 hour periods) and the 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) level, the sodium excretion content, and the urine volume were determined. The 24-hour γ-CEHC and sodium levels in the urine of the NaCl groups given 20 mg or 40 mg γ-Toc were significantly higher than those in the placebo group. The peak levels of urine sodium and γ-CEHC in the NaCl group given 40 mg γ-Toc appeared at 0–6 h, which was a more rapid increase than that seen in the group given 20 mg γ-Toc. The 24-hour urine volumes of the NaCl groups given 10 and 20 mg γ-Toc were significantly higher than the urine volume of the placebo group. Our findings suggested that γ-Toc increased sodium excretion in a dose-dependent manner in rats fed a NaCl diet. Moreover, a high dose of γ-Toc may accelerate its metabolism and cause an increase in the rate of sodium excretion

Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

Objective: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. © Published by the BMJ Publishing Group Limited

Difference in Plasma Metabolite Concentration after Ingestion of Lemon Flavonoids and Their Aglycones in Humans

The concentrations of metabolites in human plasma after ingestion of flavanone glycosides (FG) and their aglycones (FA) in lemon were examined. FG consisting abundantly of eriocitrin were prepared from lemon peel and FA consisting abundantly of eriodictyol were prepared from FG by treatment with β-glucosidase. Eriodictyol, homoeriodictyol, and hesperetin in plasma up to 4 h after ingestion of FG with water or FA with water by subjects were not detected in plasma of non-enzyme treatment but in plasma after treatment with β-glucronidase and sulfatase. Metabolites in plasma after ingestion of FG and FA in humans were shown to exist as the glucuro- and/or sulfo-conjugates of eriodictyol, homoeriodictyol, and hesperetin. After ingestion of FA, the concentration of metabolites in plasma exhibited a high maximum peak at 1 h. The AUC (area under the blood concentration time curve) level of metabolites of FA was higher than that of FG. FA were suggested to be absorbed faster and in higher amounts than FG. The AUC of metabolites in subject plasma after ingestion of FG with flavonoid-depleted lemon juice was shown to change to a low level in comparison with that of FG with water. The maximum concentration peak of metabolites in plasma was faster at 0.5 h than FA with water but the AUC level was similar to FA with water, when subjects ingested FA with vodka (40% ethanol). The absorption hour of FG and FA was shown to be affected by the co-existing solution