Since Cooley proposed and proved the possibility of two-staged heart replacement in 1969 with an artificial heart as the first stage to maintain the patient's life till a donor heart becomes available, three clinical cases have been reported by his group to date. Patients were all male and their ages were 47, 21, and 36. In the second patient the heart developed stone heart after aortic and mitral valve replacement, and a left ventricular assist device was employed instead of an artificial heart. But the patient's entire circulation was maintained for five days. All pump devices were of pneumatically-driven type and their main materials were fabric-lined silicone rubber, flock-lined polyether-type polyurethane, and Avcothane, respectively. Duration of artificial heart pumping was 64 hours in the first case and 54 hours in the third case. The pump output varied from 3.5 to 5.5l/min. All patients eventually died of infection 32 hours, 14 days, and 71/2 days after cardiac allograft transplantation. When comparing merits and drawbacks of artificial and transplantation, both therapeutic means should proceed together using the artificial heart as a temporary life-saving device.

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The survival for 125 adult HTx by donor originating from the various distant locations was compared. 10-year survival was 86%. There was no difference when comparing donors from each region despite significantly lower ischemic times in donors from area around Tokyo. Each hospital is recommended to survey risk influenced by distant donor location.

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For a long time, small children could not undergo either a heart transplantation (HTx) or heart-lung transplantation (HLTx) in Japan and many Japanese children were compelled to go abroad to undergo an HTx. After revision of the Organ Transplant Act, a small child could donate organs if the family allowed it, and in fact, eventually six children (one less than 6 years old, three from 10 to 14, and two 15 and 17) had donated his or her heart by the end of 2013. In this review, the current status of pediatric HTx and HLTx in Japan and an indication of pediatric HTx and HLTx and management before and after HTx were described. Briefly, most indications of HTx were dilated cardiomyopathy (DCM) and restrictive cardiomyopathy in Japan and many candidates with DCM required a left-ventricular assist device (LVAS) for a bridge to HTx in Japan. Patient survival at 10 years after HTx was 100% in children transplanted in Japan and 87.6% in children transplanted abroad. No child has undergone an HLTx yet. Post transplant lymphoproliferative disorder and various infections were major morbidity and mortality. Non-adherence should be paid attention, especially during the care of adolescent patients.

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ACE 阻害薬はアンジオテンシン変換酵素を阻害することにより，高血圧の原因の一つであるレニン・アンジオテンシン系を抑制することで血圧を低下させる降圧薬である．近年の研究により，降圧効果を超えた心血管系のイベントの抑制効果も指摘され，虚血性心疾患，心不全，心房細動に有効な降圧薬とされている．

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心房細動は脳梗塞をおこし半身不随をきたす恐るべき不整脈であるが,その決定的な治療法はまだない.薬物抵抗性の場合,従来の電極カテーテルを用いたアプレーションが行われているが,多数回の通電を要し,手技時間も透視時間も長く,かなりの合併症も報告されている.そこで,心房細動の発生源を焼灼する新しい高周波ホットバルーンカテーテルを開発し,実験と臨床研究を重ねた結果,本カテーテルは安全かつ短時間に心房細動の発生源を焼灼することができ,患者さんにとって福音となる治療法である可能性があると考えられる.

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An innovative Bi-Ventricular Artificial (IB-) has been successfully developed with a single magnetically suspended motor. The device has auto flow regulation function which reacts to atrial pressure change in order to balance the flow rate of left and right pump. The zero power control is adopted to control axial position of levitated impeller in the IB-Heart. The rate of change of the axial position of the impeller on the atrial pressure change is the key factor of this device's flow regulation function since the flow rate of the pumps is regulated with axial position changing of the levitated impeller. The flow regulating ability of the IB-Heart and the relationship between the rod cross-sectional area and the flow regulation function was investigated. The maglev motor was redesigned with 3-D magnetic field analysis to improve the flow regulation function.

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Objective: A statin, a potent lipid-lowering drug, improves pain-free walking distance in patients with peripheral arterial disease (PAD) without increasing the ankle-brachial pressure index (ABI). Arterial stiffness affects the blood flow of peripheral arteries. The purpose of this study was to evaluate the effect of cholesterol-lowering with atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus.
Methods: The subjects were 22 type 2 diabetic patients with hypercholesterolemia, who received atorvastatin at a daily dose of 10 mg for 6 months. Before and after the treatment with atorvastatin, we measured pulse wave velocity (PWV) in the -brachial, -carotid, -femoral and femoral-ankle segments.
Results: Following treatment with atorvastatin, femoral-ankle PWV showed a significant reduction. The PWV of other arterial segments tended to decrease, although the changes were not statistically significant. We found no significant changes in blood pressure, heart rate, ABI, or plasma concentrations of glucose, L-arginine and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial function.
Conclusions: Atorvastatin treatment was associated with an improvement in the stiffness of leg arteries in type 2 diabetes mellitus. This may partly explain the statin-mediated improvement of walking performance in those with PAD.

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近年，社会の高齢化に伴い，心不全が世界中で増加し，心不全パンデミックと呼ぶべき事態が進行している．世界に先駆け，超高齢社会に突入した日本もその例外ではなく，高齢者を中心に心不全患者数が急激に増加しており，その管理の臨床的重要性は日増しに高まっている．また，高齢化に加え，生活習慣の西欧化が進む日本では，心不全の構造自体も質的にも大きく様変わりしつつあり，注意が必要である．本稿では，日本における心不全の疫学について，海外データと比較しつつ概説する．

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悪性腫瘍の心臓転移により,心電図で持続的ST上昇を示した1症例を経験したので報告する.
症例は41歳の男性昭和59年10月,陰茎癌(扁平上皮癌)のため放射線療法(局所照射),化学療法(ペプレオマイシン)を受けるが,その後,通院しなかった,昭和60年11月より,咳漱・血痰が出現し当科を受診した.心電図でV₁-V₄,にST上昇を認め入院となった.胸痛発作の既往はなく,血清酵素の上昇はみられず,異常Q波も認められなかった.心エコー図で,左室に腫瘤を認めた.CTで左肺に転移巣を認め,12月24日には血性心膜液の貯留が見られた.臨床所見,検査成績より,陰茎癌の肺,心転移と診断した.
心電図では,持続的ST上昇が続き,徐々にST上昇は増強し,また範囲(I,aV_L,V₁-V₆)も拡大した.異常Q波は,欠如していた.
持続的ST上昇は,Rosenbaumの報告に見られるごとく,癌による心筋細胞膜の持続的な障害によると考えられる.
悪性腫瘍の心転移によるST上昇の報告は本邦ではまれであり,興味ある症例と思われた.

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The cervical heart transplantation is a new and promising device for study of pharmacology of the denervated heart. In this experiments, pharmacological studies of vasopressants, central nervous stimulants and parasympathetic drugs on the denervated heart are studied in comparison with the recipient heart in the same body.
1. As a technique for investigating the denervated heart, the usefulness of the cervical heart transplantation described by Mann, Priestley, Marcowitz and Yater was proved.
2. Highsensitivity of the denervated heart to sympathomimetic drugs was found to be in the order of epinephrine, ephedrine and nor-adrenaline.
3. On the contrary, parasympathetics evoked no highsensitivity of the denervated heart.
4. Central nerve stimulants have no action on the denervated heart.

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We simultaneously assessed effects of a specific I_f channel blocker ivabradine on the atrial and ventricular automaticity in anesthetized rabbits. Under isoflurane anesthesia, the atrioventricular node of NZW rabbits (n=3) was ablated by application of radiofrequency energy, and stable idioventricular escaped rhythm was observed. The surface lead II electrocardiogram was measured to monitor changes in the atrial rate (AR) and ventricular rate (VR). The monophasic action potential (MAP) was recorded from the right ventricle to assess the MAP duration (MAP₉₀). Intravenous administrations of ivabradine hardly affected the AR or VR at 0.01 and 0.1 mg/kg. Additional administration of ivabradine at 1.0 mg/kg decreased both AR and VR by 45 and 51 beats/min, respectively. Moreover, the MAP₉₀ was prolonged with decrease of the VR, and torsade de pointes was induced in one animal. These results suggest that ivabradine affects the ventricular as well as the atrial pacemaker activity with a similar potency.

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G-protein-gated inwardly rectifying K⁺ (GIRK) channels control various physiological functions. For example, GIRK1/2 heterotetramers in the brain regulate neuronal excitability; GIRK1/4 heterotetramers in the

regulate rate. GIRK channels are potential therapeutic targets for the treatment of several diseases, such as atrial fibrillation and addiction. In the present study, we aim to identify novel agonists/antagonists of GIRK channel and its disease-causing mutants. By electrophysiological recordings using Xenopus oocytes expressing different GIRK subunits without G-protein-coupled receptors, we screened the effect of a chemical library containing hundreds of natural products on GIRK currents. We observed that some plant alkaloids inhibit the current of wild-type GIRK1/2 and GIRK1/4 channels and some other plant alkaloids strongly inhibit a neurologic disorder-causing mutant of GIRK2 channel, G156S, which locates at the selectivity filter and induces the loss of K⁺ selectivity. Our data provided us with a clue toward the elucidation of the potential of natural products as sources of novel therapeutic agents on GIRK-targeted disease.

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Aim: This study aimed to clarify whether calcium administration has a therapeutic effect against cardiac arrest resulting from magnesium toxicity in pregnant or puerperal women, and to determine whether the body of evidence published to date suggests the need for a systematic review.

Methods: This review was guided by a specific methodological framework and Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews. Literature published up to September 24, 2020 was searched using the Medline database. Eligible articles included peer-reviewed studies in humans that prospectively or retrospectively evaluated the effects of calcium therapy on clinical outcomes and had an English abstract. Two reviewers independently screened the search results and extracted data from analyzed studies.

Results: Nineteen references were screened, and nine studies were analyzed. Five studies described maternal cardiac arrest or hypotension due to hypermagnesemia, and two studies described cardiac arrest in non-pregnant women due to hypermagnesemia. The remaining two articles were guidelines that described calcium administration for hypermagnesemia. We did not identify high-quality or large-sample studies which are needed to perform a systematic review.

Conclusions: The identified studies were insufficient to change existing recommendations. However, calcium administration may be considered for cardiac arrest associated with hypermagnesemia if ready to be performed during cardiopulmonary resuscitation.

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G-protein-gated inwardly rectifying K⁺ (GIRK) channels control various physiological functions. For example, GIRK1/2 heterotetramers in the brain regulate neuronal excitability; GIRK1/4 heterotetramers in the

regulate rate. GIRK channels are potential therapeutic targets for several diseases, such as atrial fibrillation and addiction. In the present study, we aimed to identify the effect of glycyrrhizic acid (GA), a main ingredient of licorice, and its metabolite glycyrrhetic acid (GRA) on GIRK channel activities. By electrophysiological recordings using Xenopus oocytes expressing different GIRK subunits, we observed that GA inhibits the current of heteromeric GIRK1/2 and GIRK1/4 but slightly activates the current of homomeric GIRK2 and GIRK4. This suggests that the inhibitory effect of GA is GIRK1-dependent. Mutation of a GIRK1-specific amino acid residue in the pore helix, Phe137, to Ser abolishes the inhibition of GIRK current by GA, suggesting that the Phe137 plays important roles in the sensitivity of channels to GA. Unlike GA, GRA activates all GIRK2, GIRK4, GIRK1/2 and GIRK1/4 channels. Taken together, these data indicate that GA and GRA have distinct actions on GIRK currents, and would provide clues to elucidate the diverse mechanisms of GIRK channel regulation by analyzing the difference of these compounds.

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