Atsushi Yuda

Increased local angiotensin II formation in aneurysmal aorta.

We investigated the levels and locations of angiotensin II-forming enzymes, angiotensin converting enzyme (ACE) and chymase, in aneurysmal and normal aortas. Aneurysmal aortic specimens (n = 14) were obtained at the time of operative aneurysm repair from 14 patients ranging in age from 57 to 84 y. Normal aortic specimens (n = 16) were obtained from 16 patients (48 to 72 y) who underwent coronary artery bypass surgery. The ACE and chymase activities were determined using each specimen. Sections of each specimen were immunostained with antibodies for ACE and chymase. The ACE activities in the aneurysmal and normal aortas were 0.82 +/- 0.10 and 0.14 +/- 0.05 mU/mg protein, respectively, and this difference was significant. The chymase activities in the aneurysmal and normal aortas were 17.9 +/- 2.40 and 1.02 +/- 0.18 mU/mg protein, respectively, and this difference was also significant. In the aneurysmal aorta, ACE-positive cells were detected with macrophages in the intima and media and chymase-positive cells were detected with mast cells in the media and adventitia, whereas positive ACE and chymase cells in the normal aorta were located only in the endothelium and adventitia, respectively. Angiotensin II-forming enzymes, chymase and ACE, were significantly increased in the aneurysmal aorta, and increased angiotensin II may be associated with the development of aneurysmal formations.

Inhibition of chymase reduces vascular proliferation in dog grafted veins

We investigated the effect of a chymase inhibitor Suc‐Val‐Pro‐PheP(OPh)2 on the proliferation of the grafted vein in dog. By 28 days after the operation, the mean intimal area of the grafted vein in the placebo group was 3.24±0.32 mm2. The intimal area of the grafted vein in the chymase inhibitor‐treated group was reduced to 63.9%. In the placebo group, the activities of chymase and angiotensin‐converting enzyme in grafted vein were significantly increased 15‐ and 2‐fold, respectively. In the chymase inhibitor‐treated group, chymase activity in the grafted veins was decreased significantly. These findings suggest that inhibition of chymase appears useful for preventing vascular proliferation.

Oral administration of a specific chymase inhibitor, NK3201, inhibits vascular proliferation in grafted vein.

Chymase may play an important role in vascular proliferation, as shown by in-vitro experiments, but the role of chymase in vivo has been unclear. In this study, we investigated the effect of a novel chymase inhibitor, NK3201, on this proliferation in dog grafted veins. NK3201 inhibited human and dog chymases, but not rabbit ACE. NK3201 suppressed the Ang I-induced vascular contraction in isolated dog arteries in the presence of an ACE inhibitor, and the IC50 value of chymostatin and NK3201 in dog artery was 320 nM. In dog, the concentration of NK3201 in blood was about 10 microM at 24 h after oral administration of the drug (5 mg/kg). In the group treated with NK3201, each dog was administered orally 5 mg/kg per day from 5 days before to the day before the removal of the grafted veins. Each dog underwent right common carotid artery bypass grafting with the ipsilaterial external jugular vein. By 28 days after grafting, a significant vascular proliferation was observed in the grafted veins and the chymase activity was also increased significantly. Treatment with chymase inhibitor significantly suppressed the proliferation of the grafted veins and the increased chymase activity. In this study, we demonstrate for the first time that oral administration of a specific chymase inhibitor, NK3201, appears useful for preventing vascular proliferation.

Angiotensin II receptor antagonist, L-158,809, prevents intimal hyperplasia in dog grafted veins.

We investigated the levels of the angiotensin II-forming enzymes, chymase and angiotensin converting enzyme (ACE), in dog grafted veins, and studied the effect of an angiotensin II type 1 receptor antagonist, L-158,809, on vascular proliferation in the grafted veins. The right external jugular vein was grafted to the ipsilaterial carotid artery. In the group treated with L-158,809, the drug (10 mg/kg per day, p.o.) were administered orally from 7 days before the operation to 28 days after it, while the others were administrated placebo. In the placebo-treated group, the chymase activity in the grafted veins was increased about 10-fold and the ACE activity was doubled. The areas of intima and media were significantly increased in the grafted veins in the placebo-treated group. L-158,809 significantly reduced the intimal area of the grafted veins. An angiotensin II receptor antagonist, L-158,809, prevented the vascular proliferation in the grafted veins, and the development of the proliferation may depend on activation of local angiotensin II formation.

Cilostazol suppresses intimal formation in dog grafted veins with reduction of angiotensin II-forming enzymes

Cilostazol prevents neointimal formation, but its mechanism has remained unclear. We investigated whether intimal formation in dog grafted veins is suppressed by cilostazol, and studied the effect of cilostazol on angiotensin II-forming enzymes. The external jugular vein was grafted to the carotid artery, and cilostazol (60 mg/kg/day) was administered orally. By 28 days after the surgery, the intimal cross-sectional area of the grafted vein was reduced to 16.7% by treatment of cilostazol, and the activities of angiotensin II-forming enzymes were suppressed significantly. The inhibitory effect of cilostazol in intimal formation may be dependent on inhibition of angiotensin II-forming enzymes.

A case report of infective endocarditis caused by MRSA and characterized by pedicled vegetation on the posterior wall of left atrium

We report here a case of active infective endocarditis caused by Methicilin-Resistant Staphylococcus aureus (MRSA). A 24-year-old woman was admitted to the Osaka Medical Collage Hospital with continuous fever. After admission, MRSA was detected by blood culture and chemotherapy with Vancomycin was started. However, after 1 week, her condition had not improved. Moreover, a pedicled vegetation on the posterior wall of the left atrium and mitral regurgitation due to prolapse of the anterior leaflet were revealed by transesophageal echocardiography. The vegetation grew to about 2 cm in diameter and prolapsed into the left ventricle during diastole. We performed an early operation although the infection was still active due to its rapid growth and the risk of embolism. There was a large pedicled vegetation on the posterior wall of the left atrium as shown by preoperative echocardiography, but the mitral valve appeared to be intact. Therefore, the vegetation was completely removed and the mitral annulus was plicated by Kays method to treat the associated mitral regurgitation. Postoperatively, we administered VCM 2 g/day for 24 days. The course was uneventful. The patient was discharged from the hospital on the 31st postoperative day.

Vacuum-assisted closure for postcardiac surgery mediastinitis in a patient on hemodialysis

A 66-year-old man on hemodialysis underwent off-pump coronary artery bypass grafting. He was discharged in good condition on postoperative day (POD) 16. A high-grade fever and a purulent discharge emerged on POD 30. Methicillin-resistant Staphylococcus aureus was identified by culturing material from the wound. On admission, vacuum-assisted closure (VAC) therapy was applied for 80 days. Finally, good wound healing allowed us to perform simple wound closure without using muscle flaps or omentoplasty. VAC therapy is a useful and safe procedure for postcardiac surgery mediastinitis.

An Operative Case of Chronic Traumatic Thoracic Aortic Aneurysm, 19 Years after a Traffic Accident

交通外傷後19年を経過し,偶然発見された慢性外傷性胸部大動脈瘤の1例を経験した.本症例は交通外傷後19年目に突然,胸部違和感が出現したため精査を施行され,食道粘膜下腫瘤と診断されたが胸部CT検査で大動脈峡部に最大径7.5cm×5.5cmの胸部下行大動脈瘤を認めた.これまでの経過から,慢性外傷性胸部大動脈瘤と診断した.慢性外傷性胸部大動脈瘤は無症状であっても放置すると瘤径拡大を認めるという報告もあり,診断がつけば積極的に手術を行うべきである.手術方法には,1)ステントグラフト内挿術と2)人工血管置換術があるが,ステントグラフトのendoleak,migrationといった合併症を考慮し,確実性を求め,今回は人工血管置換術を選択した.補助手段については慢性期症例では急性期に比し,出血の危険性が少ないことから,患者の状況に応じて左心バイパス法,:F-Fバイパス法,一時バイパス法を使い分けることが肝要である.