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Treatment with low-dose prasugrel might be more beneficial even in chronic stable coronary artery disease (CAD) patients treated with clopidogrel. We compared platelet reactivity between standard maintenance-dose and low-dose prasugrel in stable CAD patients.This multicenter study enrolled 164 stable CAD patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Patients were randomly assigned to continue treatment with 75-mg clopidogrel daily (n = 80) or switch to 3.75-mg prasugrel daily (n = 84). Platelet reactivity was evaluated by measuring P2YThe PRU level was comparable between the two groups at baseline but was significantly lower in the prasugrel group than in the clopidogrel group on days 5 (133.0 vs. 156.8 PRU, P = 0.005) and 30 (124.3 vs. 158.0 PRU, P 0.001). On day 30, the PRU level was lower in the prasugrel group among patients categorized as poor and intermediate metabolizers but not among extensive metabolizers.Low-dose prasugrel achieves more consistent antiplatelet effects than clopidogrel irrespective of the metabolic phenotype in Japanese patients with stable CAD. Low-dose prasugrel might be also beneficial in the chronic phase without increasing the bleeding risk among stable CAD patients in other countries.

ObjectiveParaplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.MethodsEighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4°C) and fasudil (group 2, n = 6, 4°C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.ResultsTwo days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.ConclusionThese results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.Clinical RelevanceParaplegia or paralysis caused by spinal cord ischemia remains a devastating and unpredictable complication after descending and thoracoabdominal aortic surgery. This study has revealed that fasudil has a neuroprotective effect against ischemic spinal cord injury in rabbits. Inhibition of the Rho/Rho kinase pathway by fasudil reduces the number of infiltrating cells in the ventral horn and prolongs the expression of eNOS. In the near future, Rho kinase may be an important therapeutic target for paraplegia induced by spinal cord ischemia.

We analyzed the mid-term left ventricular (LV) performance after aortic valve replacement (AVR). We measured LV contractility (end-systolic elastance: Ees), afterload (effective arterial elastance: Ea) and efficiency (ventriculoarterial coupling: Ea/Ees; ratio of stroke work and pressure-volume area: SW/PVA) based on transthoracic echocardiography data obtained before, after and approximately 1 year after isolated AVR in 263 patients with aortic stenosis (AS group; n=116), aortic regurgitation (AR group; n=93) or aortic stenosis and regurgitation (ASR group; n=54). The LV volume was calculated by the Teichholz M-mode method. Ees and Ea were approximated as follows: Ees=mean blood pressure/minimal LV volume; Ea=systolic blood pressure/(maximal LV volume-minimal LV volume). Thereafter, Ea/Ees and SW/PVA were calculated. Arterial blood pressure was measured using manchette methods. Ees and Ea decreased after AVR in the AS group, but increased in the AR group. Ea/Ees and SW/PVA worsened after AVR in the AR group, but improved during a 1-year period after AVR in all groups. Contrasting effects of AVR on LV contractility and afterload between AS and AR were clearly demonstrated. The mid-term LV contractility and efficiency after AVR were excellent and satisfactory. However, LV efficiency worsened early after AVR in AR patients.

開心術周術期に治療抵抗性の難治性心筋虚血（冠動脈スパズムを含む）を発症した6例に対し，Rho-kinase阻害剤である塩酸ファスジルを使用した．術後急性期に発症した3例は年齢49～81歳，男性2例，女性1例であった．術直後～手術3時間後にST上昇を伴う循環虚脱を来たした．緊急冠動脈造影を行ったところ，冠動脈あるいはバイパスグラフトのスパズムを認めた．硝酸イソソルビド（ISDN）の冠動脈内投与を行うも軽快が得られなかったため，塩酸ファスジルをスパズム発症血管に対し選択的に投与したところ，3例ともに解除に成功した．術中に発症した3例は年齢57～77歳，いずれも男性であった．大動脈遮断解除後，心膜切開直後，バイパスグラフト吻合中に心筋虚血を発症した．ISDN無効あるいはスパズム疑診例であったため塩酸ファスジルを投与したところ，血行動態の安定化が得られ3例とも術中に体外循環を離脱し得た．スパズムと確定診断された症例はもとより，他剤無効例，スパズム疑診例に対しても塩酸ファスジルは有効であった．Rho-kinaseを標的とした治療戦略は，冠動脈スパズムを含む周術期難治性心筋虚血に対する新たな治療手段となり得る．

We have developed an ultraminiature centrifugal pump, TinyPump, with a priming volume of 5 ml. The in vivo performance of TinyPump was compared with that of HPM-05 for left ventricular support. Each pump group included seven rabbits weighing 3.4-3.8 kg. One rabbit in the TinyPump group and two rabbits in the HPM-05 group died of unsuccessful cannulation. The remaining rabbits (six in the TinyPump group and five in the HPM-05 group) were instrumented and observed for 240 minutes. The pump flow was maintained at around 200 ml/min. The priming volumes of the entire circuits were 25 and 45 ml for TinyPump and HPM-05, respectively. TinyPump required a higher rotation speed (2214 +/- 47 vs. 1261 +/- 87 rpm, p < 0.05) because of its small priming volume but showed a similar plasma free hemoglobin level to HPM-05. The hematocrit values were kept higher in the TinyPump group during ventricular support (24.3 +/- 1.4% vs. 20.1 +/- 1.4% at 240 minutes, p < 0.05). The mean arterial pressure did not differ between the two groups. The biochemical parameters were also equivalent in the two groups. Overall, TinyPump exhibited a feasible in vivo performance. This ultraminiature device would offer promising outcomes for neonates and infants with intractable heart failure.

Prolonged support with left ventricular assist system (LVAS) increases the risk of device-related infection. We experienced a rare complication of LVAS: an infectious aneurysm at the apical cannula, which appeared with atypical presentation. A 27-year-old male, who developed acute aggravation of dilated cardiomyopathy, was placed on extra-corporeal type LVAS. Six months later, the patient suffered from methicillin-resistant Staphylococcus aureus (MRSA) sepsis that lasted for as long as three months despite intensive antibiotic therapy. At 17 months after the implantation, he presented with obstructive ileus. Monthly assessment with transthoracic echocardiography (TTE) did not document any abnormalities around the ventricle. A contrast computed tomographic (CT) scan revealed a huge apical aneurysm protruding into the preperitoneal space. The aneurysm oppressed the transverse colon, resulting in obstructive ileus. Aneurysmectomy was carried out and MRSA was identified from the resected tissue. We reached the precise diagnosis with a CT-scan, although routine assessment with TTE failed to reveal abnormalities. Knowledge of this complication is essential in LVAS management. This is certainly rare, but possibly occurs in all the patients on prolonged LVAS support. Early and accurate diagnosis together with aggressive intervention would bring favorable outcome in such serious cases.