遊離広背筋によるCardiomyoplastyにおける除神経と神経移植の影響

金沢大学医学部附属病院左広背筋によるCardiomyoplastyにおいて,広背筋の中枢側を使用しようとすると,胸背神経を切離しなくてはならず,そこには除神経による筋萎縮が障害となってくる.除神経による弊害は筋の萎縮,筋内グリコーゲンの減少,収縮特性の変化,等が報告されており,cardiomyoplastyにおいては不利な変化である.今回は,遊離広背筋による除神経の影響を検討した.まず同一の雑種成犬の一側の広背筋において胸背神経を切断し,両側の広背筋の慢性電気的刺激にて,両側の筋肉重量を測定した結果,神経切断側の筋重量は非切断側に比し有意に低値であった(145g vs 186g,p<0.05).顕微鏡所見では切断側のは筋萎縮,筋の繊維化が認められた.除神経は慢性期において骨格筋を用いたcardiomyoplastyにとって避けるべき条件と考えられた.広背筋を有茎で心臓に縫着した群と,遊離広背筋で縫着した群では血行動態に有意な差を認めた.すなはち骨格筋の駆動により,有茎群では心拍出量が32%上昇したのに比し,有茎群では12%の上昇にとどまった.肉眼的,光顕的にもにも有茎,すなはち除神経された広背筋には萎縮を認めた.これに対して有茎広背筋を用いた群において,胸背神経を肋間神経に移植吻合する実験を行ったが,神経切断のままの群との差はなかった.神経吻合は今回の研究では成功しなかった.以上の結果より臨床において,cardiomyoplastyには従来の有茎移植が望ましいと考えられるが,今後神経移植の新しい方法が模索される意義は大きいと考えられた.研究課題/領域番号:07771036, 研究期間(年度):1995出典：研究課題「遊離広背筋によるCardiomyoplastyにおける除神経と神経移植の影響」課題番号07771036（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-07771036/）を加工して作

Cardiomyoplastyにおける人工二重心膜による骨格筋癒着防止と硬化

金沢大学医薬保健研究域医学系【目的・方法】Cardiomyoplastyにおいて心臓に巻き付けた骨格筋が胸骨,心膜に強固に癒着し,骨格筋が自由に動けず,心機能補助に制限があることが報告されている.これまでの我々の研究においても慢性期に開胸してみると,骨格筋が胸骨に強固に癒着しており,非開胸時より癒着剥離の為心機能が著明に改善することが観察されていた.骨格筋の癒着を防止しなめらかな自由な骨格筋運動をさせるために人工心膜を考案し,その有効性を検討した.人工心膜の素材としては今回はPTFEを用い二重構造のsacを作成し心臓をくるめるように形成し,中空に水,オリーブ油を充填した.Cardiomyoplastyのモデル作製.成犬雑種10頭を用い,全身麻酔下に左広背筋を遠位付着部位で剥離遊離し,第3肋骨切除部位から有茎に広背筋を胸腔内に誘導し,心臓に巻き付けるように心外膜に固定した.その外側に作製した人工心膜を心臓ならびに骨格筋を包むように固定した.骨格筋に電気刺激用のペースメーカーリ-ドを縫着し,連続刺激ペースメーカーを接続した.手術終了後2週間後からペースメーカーで広背筋を刺激し,2カ月トレーニングし,非疲労性の筋へtransformationさせた.2カ月後人工心膜の効果を評価した.【結果】人工心膜の中空状態の作成に難渋し,中に充填した生理食塩水,オリーブ油は2ヶ月後には消失していた.また内外のPTFE膜は癒着しており,初期の目的のなめらかな人工心膜作成には至らなかった.心エコーを用いても骨格筋の外面は周囲と癒着しており,人工心膜を巻かないコントロール群と比較しても差はなかった.以上の結果から人工心膜の素材の選択,確実に中空を保てるsacの作成方法に問題があった.cardiomyoplastyは充分臨床応用可能で,今後は如何に効率よく骨格筋駆動の効果を引き出すかが課題で,今回の人工心膜もその一つの解決方法と思われる.研究課題/領域番号:08771016, 研究期間(年度):1996出典：研究課題「Cardiomyoplastyにおける人工二重心膜による骨格筋癒着防止と硬化」課題番号08771016（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-08771016/）を加工して作

骨格筋による右心不全に対する急性期および慢性期の心機能補助効果に関する実験的研究

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1214号, 学位授与年月日：平成5年2月17日,学位授与年：199

Cardiomyoplastyの骨格筋発育へのPGE、蛋向同化ホルモンの影響

金沢大学医学部・附属病院Cardiomyoplastyにおいて,骨格筋の発育に関して,今回はプロスタグランジンの影響を検討した.プロスタグランジンは既に閉塞性動脈硬化症において毛細血管のネットワークを発達させ,虚血改善を目的に臨床応用されている.心臓に巻き付けられた広背筋は,胸壁からの血流を遮断され,胸背動脈のみで血液供給を受けており,特に広背筋末梢においては虚血が広背筋の発育に悪影響を与える.プロスタグランジンを投与した群においては,広背筋の筋重量は非投与群に比べて有意に大きく,非投与群においては広背筋の虚血性萎縮に伴う筋量減少があり,プロスタグランジン投与群においてはその虚血性萎縮が回避できたものと考えられた.骨格筋駆動時と非駆動時の心拍出量の増加率はプロスタグランジン非投与群で141%であったのに対して,プロスタグランジン投与群では161%の増加率であり,2群間には有位差を認めた.骨格筋駆動後の動脈圧上昇率は非投与群で120%であったのに対して,投与群では132%と投与群で上昇率が高い傾向にあった.中心静脈圧は非投与群で6mmHgで投与群の4mmHgと比し優位に低かった.以上よりプロスタグランジン投与群では骨格筋の駆動により,比投与群に比べて血行動態の改善が著明であった.以上の原因と思われる細動脈の発達の相違をみるために堵殺後胸背動脈から造影剤を注入し,レントゲン撮影を行い,2群間で比較した.今回は血管量を客観的な方法で検討していないが,プロスタグランジン投与群では非投与群に比し,細動脈の副側血行の発達が著明で,プロスタグランジンは骨格筋の電気的刺激トレーニングにおいて有効な骨格筋発育を促す方法として期待できると考えられた.研究課題/領域番号:06771015, 研究期間(年度):1994出典：研究課題「Cardiomyoplastyの骨格筋発育へのPGE、蛋向同化ホルモンの影響」課題番号06771015（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-06771015/）を加工して作

Total arterial revascularization with composite skeletonized gastroepiploic artery graft in off-pump coronary artery bypass grafting

AbstractBackgroundTotal arterial revascularization in coronary artery bypass grafting has recently become of great interest to many surgeons. At the same time, off-pump coronary bypass grafting has also become a popular procedure because of its low morbidity and mortality. Here we report our recent series of off-pump coronary bypass grafting performed with a grafting technique we developed by using the skeletonized gastroepiploic artery and the radial artery composite graft to achieve total arterial revascularization.MethodsFrom September 2000 to April 2003, 98 patients underwent total arterial revascularization with the skeletonized gastroepiploic artery and radial artery composite graft on the beating heart. We used the gastroepiploic artery graft of choice in patients with a right coronary artery lesion. When multiple grafting was required in inferior, posterolateral, or lateral ventricular walls and the gastroepiploic artery graft was too short to cover these areas, we used the composite grafting technique.ResultsThere were no in-hospital deaths and there was no severe morbidity among the study patients. Postoperative angiography showed graft occlusion at the anastomosis site between the gastroepiploic and radial arteries. The patency rate of the gastroepiploic arterial composite graft was 98.3% (118/120 distal anastomoses).ConclusionsA composite graft with the skeletonized gastroepiploic artery and the radial artery ensured sufficient caliber size and length for myocardial revascularization on inferior, posterolateral, and lateral ventricular walls. This composite graft can be used safely and effectively even in off-pump coronary bypass surgery with excellent early clinical and angiographic outcome in selected patients, although longer follow-up periods are necessary to draw definitive conclusions

Prevalence and clinical manifestations of gastro-oesophageal reflux-associated chronic cough in the Japanese population

Gastro-oesophageal reflux (GOR) is one of the most common causes of chronic cough in Western countries, responsible for 10 to 40% of cases. In Japan, however, GOR-associated chronic cough (GOR-CC) has been rarely reported and its clinical manifestation including frequency of concomitant reflux laryngitis is poorly known. We have analyzed prevalence and clinical characteristics of patients who were diagnosed as having GOR-CC among adult patients with chronic cough (≥ 8 weeks) who visited our asthma and cough clinic over a period of 19 months. Diagnosis of GOR-CC was based on the response of coughing to a proton-pump inhibitor (lansoprazole™) and/or positive results of 24 h ambulatory esophageal pH monitoring. Laryngeal involvement was based on symptoms or objective diagnosis by specialists. GOR-associated chronic cough was diagnosed in 7.1% (8 of 112) of chronic cough patients. In addition to the demographic data which were consistent with the characteristics of patients with GOR-CC in the Western populations, including gender (6 females), age (mean ± SE, 56.9 ± 5.8 years), duration of cough (9.9 ± 3.3 months), lack of gastrointestinal symptoms (3 of 8) and complication with other causes of cough (5 of 8), we found the standard range of body mass index (23.9 ± 1.5 kg/m(2)) and high incidence of concomitant reflux laryngitis (5 of 8) in the present 8 patients. Among 4 patients who could stop treatment with temporal resolution of cough, cough recurred in 3 patients, 1 week to 8 months after the discontinuation. In conclusion, GOR-CC is a less frequent cause of chronic cough in Japan than in Western countries. Signs or symptoms of laryngitis may be important as clues to suspicion of GOR-CC

Serotonin enhances the production of type IV collagen by human mesangial cells

Serotonin enhances the production of type IV collagen by human mesangial cells.BackgroundThe plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT2A receptor in mesangial cells. Because expansion of the glomerular mesangial lesion is a characteristic feature of diabetic nephropathy, we examined the effect of 5-HT on the production of type IV collagen by human mesangial cells.MethodsHuman mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor-β (TGF-β) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF-β mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively.Results5-HT stimulated the production of type IV collagen by human mesangial cells, which was inhibited by ketanserin and sarpogrelate hydrochloride, 5-HT2A receptor antagonists, but not by ondansetron, a 5-HT3 receptor antagonist. 5-HT increased the bioactivities of both active and total TGF-β. However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF-β antibody. Furthermore, a PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV collagen secretion, and the activity of membrane PKC was increased by 5-HT. Phorbol ester activated type IV collagen production as well as active and total TGF-β. Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF-β, but did not inhibit exogenous TGF-β-induced increase in type IV collagen secretion.ConclusionsOur results suggest that 5-HT-enhanced production of type IV collagen by human mesangial cells is mediated by activation of PKC and subsequent increase in active TGF-β activity

Features of cough variant asthma and classic asthma during methacholine-induced brochoconstriction: a cross-sectional study

[Background]Little is known regarding mechanistic and phenotypic differences between cough variant asthma (CVA), presenting with a chronic cough as the sole symptom that responds to bronchodilators, and classic asthma with wheezing during methacholine inhalation. Here we reported airway sensitivity, airway reactivity, and as the main concern, the appearance of cough and wheezes during methacholine inhalation in patients with CVA or classic asthma. [Methods]We cross-sectionally examined the degrees of airway sensitivity, the point where resistance started to increase, and reactivity, the slope of the methacholine-resistance curve, and the appearance of cough and wheezes in steroid-naive adult patients with classic asthma (n = 58) or CVA (n = 55) while they were continuously inhaling methacholine during simultaneous measurement of respiratory resistance. [Results]Patients with CVA were less sensitive and less reactive to inhaled methacholine and wheezed less frequently but coughed more frequently during methacholine-induced bronchoconstriction than did patients with classic asthma. Multivariate analysis revealed that airway hypersensitivity and lower baseline FEV1/FVC were associated with the appearance of wheezes, whereas a diagnosis of CVA was associated with coughing. [Conclusion]There are mechanistic and phenotypic differences between CVA and classic asthma during methacholine inhalation. Frequent coughing during bronchoconstriction may be a distinctive feature of CVA