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拡張型心筋症(心不全)と自律神経の関係

心不全(特に拡張型心筋症)の原因と予防

未だに原因不明とされている心筋症(心不全)ですが、医師の中には「生活習慣が起因」「心臓組織へのウィルス侵入説」「遺伝子の異常」「先天性奇形」等など、様々な意見に別れ、得策がないため予後不良として、薬物療法・ペースメーカーの植え込み・心臓移植と消極的なネガティブ情報しかない状況です。

そもそも、心不全で一番死亡率が高いと言われている「特発性拡張型心筋症」。心筋梗塞や狭心症など、疾患経験がないのにある日突然に咳や呼吸困難、足のむくみ、不整脈、心拍数の上昇によって救急搬送され、XP(レントゲン)や血液検査、心臓エコーなどの検査を経て、緊急入院。
ドブタミン(強心点滴液)連続シリンジ投与やヘパリン静注点滴、飲水制限・食事の管理、様々な投薬によって、寛解状態にて退院。その後は自宅通院によって、処方薬指示や心臓リハビリを余儀なく実施し、これ以上増悪しなように安静指示が出されます。

自宅療養中は、かなり厳しい制限が指示されます。
1.塩分制限 6g/日以内
2.水分制限 (重症患者)500cc~800cc (中程度患者)1000cc~1500cc
3.禁煙指示 一酸化炭素の吸引を継続すると、血管壁に存在する自律神経を刺激し、血管狭窄(イレウス)のために起こる血圧上昇にて心臓に負担がかかる。
4.飲酒制限 肝機能の代謝分解能により、分解が機能しない場合は禁酒。
5.体重測定・血液量の自主的管理(1~3日での体重増加があれば利尿剤にて負担軽減)
6.投薬管理 不整脈の増加や呼吸困難発症があれば、投薬の干渉があるため、主治医とカンファレンス。
7.運動制限 ジョギング禁止・重労働禁止・症状によっては自動車の運転禁止(心リハでの有酸素運動は予後改善)

上記のように厳格にこれらを厳守しても、心筋症という疾患は進行性であり、決して完治はしないとされている。

しかし、上記7項目以外に重要な事項が欠落していることが、当研究所の研究で判明している。
それは、自律神経に対する所見である。即ち、過剰なストレスと心筋症との因果関係である。
心臓の筋肉は、洞結節と言う「発電所」で一定の電気信号を自動的に作り出し、その信号を心房や心室へ拡散することによって、心筋を収縮させている。言わば、人体のペースメーカーである。しかし、一定のリズムで拍動する心筋ではあるが、脳や自己意識で自由にコントロールすることはできない。このペースメーカ的同結節をコントロールしているのが、全身の血管側壁に張り巡らされている「自律神経」である。
自律神経は、書いて字のごとく自立した神経ということが言える。例えば、夜道の暗がりで急に凶器を持った人物に遭遇すれば、誰しもが心拍数が上昇し、血圧は最高値まで上昇、更には全身の発汗現象と瞳孔散開が起きる。
この生体反応は、自律神経の交感神経が優位になり、脳からアドレナリンを放出し、逃げるか攻撃するかの準備をしているのである。
これらの反応を意識してできる生物は、この地球上では皆無である。

そこで当研究所では、過剰なストレスを受けた場合の自律神経と心筋や血管の動向を観察し、どれほどの負荷が心筋に影響するのかを、臨床試験で得てみた。
現在は臨床試験途上ではあるが、心筋や心筋細胞にかなりのダメージを受けていることや、心筋損傷を確認した。

確認事項:
血液検査:特にBNP値・赤血球数・白血球数・リンパ球数・免疫細胞の変形など。

まだ、推論の域は出ていないが、恐らく過剰なストレスが継続した場合に、心臓に多大な負荷がかかることと、血管の収縮や高血圧によって心不全(特に拡張型心筋症)に成りうるのではないかと言う仮説をベースに、現在は臨床試験継続中である。


今後の予定:

第二臨床試験として、予防医学の観点からテアニン*1と言う成分を投与したグループとしなかったグループに分け、二重盲検法(にじゅうもうけんほう、英: Double blind test)にて実施確認を行う。注1テアニンの説明は別紙にて

L-Theanine Scientific Name(s): Gamma-ethylamino-L-glutamic acid ; derived from Boletus badius and Camellia sinensis . Common Name(s): L-theanine , Suntheanine Uses L-theanine may help relieve stress by inducing a relaxing effect without drowsiness and may also possess immunologic attributes. Theanine may also have effects on the cardiovascular system and play a preventative role in cancer; however, limited clinical information is available to support these claims. Dosing Data supporting a clinical role for theanine are weak. Studies reporting an anxiolytic effect used single doses of theanine 200 to 250 mg. Contraindications None well established. Pregnancy/Lactation Information regarding safety and efficacy in pregnancy and lactation is lacking. Interactions None well documented. Adverse Reactions Few adverse reactions have been reported. Adverse reactions recorded in human pharmacokinetic studies using tea extracts include headache, dizziness, and GI symptoms. Toxicology Theanine is sold in the United States as a dietary supplement and has been granted GRAS (generally recognized as safe) status by the Food and Drug Administration (FDA). Botany Theanine is derived from the leaves of Camellia sinensis (tea) and 2 other Camellia species ( Camellia japonica and Camellia sasanqua ). C. sinensis is native to eastern Asia and is a member of the Theaceae family. This evergreen shrub or tree grows to over 9 m in height and is pruned from 60 cm to 1.5 m for cultivation. Its dark green, serrated-edged leaves are alternate and oval, while its white and fragrant blossoms appear singly or in clusters. 1 , 2 The chemical has also been isolated from the edible mushroom Boletus badius , although information is limited to a single 1960 publication. 3 The mushroom is commonly found in late summer and autumn in the United States, and is reddish brown to dark brick/brown in color with a 4 to 12 cm tall stem. The flesh is white to yellow in color, and becomes a light blue/green color when cut or bruised. History Second only to water, tea is the most widely consumed beverage in the world. L-theanine was discovered as a constituent of green tea in 1949 and was approved in Japan in 1964 for unlimited use in all foods, including chocolates, soft drinks, and herb teas, except infant foods. It also provides a unique umami (brothy or savory) taste and flavor to green tea infusion. 2 , 4 Chemistry L-theanine (or L-gamma-glutamylethylamide) was discovered in 1949 and constitutes 1% to 2% of the dry weight of tea leaves. It exists only in the free (nonprotein) form. An enzymatic method for manufacturing synthetic L-theanine ( Suntheanine ) has been developed. 2 , 4 , 5 Uses and Pharmacology Cancer Limited studies evaluate the effects of L-theanine in the prevention of cancer. A Cochrane meta-analysis of the effects of green tea in cancer has found insufficient and conflicting evidence to support a preventative role. 6 The observed anticancer effects are largely attributed to the catechins found in tea, 6 while action on tumors may be due to an enhanced immune response. 7 Cardiovascular effects A dose-dependent hypotensive effect was demonstrated in spontaneously hypertensive rats, but not in normotensive ones. The effect may have been related to reduction in central levels of dopamine and serotonin. 2 In healthy volunteers, synthetic theanine 200 mg muted the increase in heart rate response to an acute stress test, 8 while theanine has been observed to antagonize the hypertensive effect of caffeine. 9 L-theanine exerts a weak (compared with green tea) antioxidant action as measured by the inhibition of LDL oxidation. 2 , 10 CNS effects Although the pharmacological effects of theanine are uncertain, several researchers have proposed a number of mechanisms by which it may act on the CNS. These include the inhibition of glutamate receptors, increasing the concentration of gamma-aminobutyric acid (GABA), increasing dopamine and serotonin in specific brain regions, and neuroprotective blockage of multiple glutamate receptor subtypes in the hippocampus, suggesting a potential role in Parkinson disease. 5 , 11 , 12 Clinical data L-theanine is able to cross the blood-brain barrier, and most research has focused on its relaxing effect. Studies have evaluated the effect of theanine alone or in combination with caffeine in concentrations naturally found in tea, and use self-reporting measures of stress and electroencephalographic recordings of brain activity. However, study data are inconsistent in methodology and outcome measures, making comparisons difficult. 4 , 8 , 9 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 An effect of wakeful relaxation of theanine alone is apparent in most published data. The effect is weak in comparison with benzodiazepines, and may differ with consumption of theanine in the relaxed state versus an already anxious state. Some studies suggest a positive contribution to cognitive performance. 5 , 11 , 17 , 21 Immune system functioning A limited number of studies conducted primarily by 2 groups of researchers suggest L-theanine may enhance the action of immune system components. Results of in vitro studies, a pilot study, and a small clinical trial suggest that the enhancement of gamma delta T lymphocytes may play a role in the observed decrease in cold and influenza symptoms. A combination preparation was used in the clinical trial. 7 , 22 , 23 Other researchers have evaluated the combined effect of L-cystine and L-theanine on the immunologic response to vaccinations in the elderly and to exercise in athletes, as well as in rats, and suggest an enhanced immunologic response. 8 , 24 , 25 , 26 Other effects L-theanine showed no hepatoprotective effect in an in vitro study. 27 Dosage L-theanine crosses the blood-brain barrier, with effects evident within 30 minutes and measurable up to 5 hours after administration. 5 , 15 , 19 The chemical is metabolized in the kidneys to glutamic acid and ethylamine. 28 Data supporting a clinical role for theanine are weak. Studies reporting an anxiolytic effect used single doses of theanine 200 to 250 mg. 8 , 9 , 16 , 17 , 20 No dosage of L-theanine is suggested for enhanced immune system functioning. Pregnancy/Lactation Information regarding safety and efficacy in pregnancy and lactation is lacking. 29 Interactions Clinical data are limited. L-theanine counteracted the stimulatory effect of caffeine in rats, although at smaller doses excitatory effects were observed. 2 Adverse Reactions Information regarding adverse reactions to theanine alone (versus combined with caffeine, as in tea) is lacking. Clinical trials used small numbers of participants and reported poorly on adverse events. One study among elderly participants recorded a higher number of reported headaches among those receiving 4 doses of theanine 250 mg. 16 There are no reports of clinical toxicity from daily tea consumption. Adverse reactions recorded in human pharmacokinetic studies using tea extracts include headache, dizziness, and GI symptoms. 6 Toxicology Theanine is sold in the United States as a dietary supplement and has been granted GRAS status in doses up to 250 mg per serving by the FDA. 30 The median lethal dose (LD 50 ) of L-theanine is suggested to be 5 g/kg. Mutagenicity and acute and subacute toxicity tests have failed to show toxicity of synthetic L-theanine. 4 A toxicological study in rats showed no effect on behavior, morbidity, mortality, body weight, hematology, or urinalysis. An increased incidence of renal tubule adenomas in a small number of female rats given high dosages (400 mg/kg body weight per day) was attributed to genetic predisposition. 31

  • Category:医療
  • Author:管理者