Hideki Kawaguchi

Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism.

Insulin-like growth factor-I (IGF-I) has been shown to produce a short-term positive inotropic effect (PIE) in the myocardium under nonischemic conditions. IGF-I also conferred cytoprotection against ischemia and reperfusion injury in various organs. IGF-I may, therefore, facilitate the recovery of postischemic cardiac function. Isolated and crystalloid-perfused rat heart was subjected to 25 min of normothermic ischemia followed by 30 min of reperfusion. IGF-I produced PIE in a dose-dependent manner at concentrations ranging between 1 and 100 nM under nonischemic conditions. Although 1 nM isoproterenol produced much greater PIE and myocardial energy conversion efficiency (MECE) than did 65 nM IGF-I in this condition, the same concentration of IGF-I administered during reperfusion conferred better recovery of left ventricular function and MECE compared with isoproterenol. The improved cardiac performance by IGF-I was associated with lower release of creatine kinase (CK). Wortmannin (100 nM), a specific inhibitor of phosphatidylinositol kinase (PI-3 kinase), abrogated IGF-I-induced improvement of contractile function and inhibition of CK release in the postischemic heart. We conclude that IGF-I administered during reperfusion accelerates recovery of cardiac performance and mitigates myocardial injury through a wortmannin-sensitive mechanism.

Effects Of The Na+/H+ Exchange Inhibitor Cariporide (HOE 642) On Cardiac Function And Cardiomyocyte Cell Death In Rat Ischaemic–Reperfused Heart

1. Na+/H+ exchange has been implicated in the mechanism of reperfusion injury. We examined the effects of the cardiac‐specific Na+/H+ exchange inhibitor cariporide (HOE 642) on postischaemic recovery of cardiac function and cardiomyocyte cell death (i.e. necrosis and apoptosis).

Potential role of vacuolar H+–adenosine triphosphatase in neointimal formation in cultured human saphenous vein☆

OBJECTIVE Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. METHODS AND RESULTS Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.

One stage operation for aneurysm of the diverticulum of the ductus arteriosus and coronary artery bypass grafting

Aneurysm of the diverticulum of the ductus arteriosus in the adult is rare. One stage operation for aneurysm of the diverticulum of the ductus arteriosis and coronary artery bypass grafting (CABG) is reported. A 61-year-old man was admitted for diagnosis of thoracic aneurysm on chest X-ray and CT. Chest CT scan showed an aneurysm above the left main pulmonary artery. An aortography showed the left vertebral artery originated directly from the aortic arch and a saccular aneurysm arising from the aortic isthmus and lesser curvature of the aortic arch. Coronary arteriography showed 75% stenosis at the right coronary artery (seg. #1) and 75% stenosis at the left anterior descending artery. Operation was performed through a median sternotomy. The aneurysm of 6 to 3 cm was located between the aortic isthmus and left pulmonary artery. Ascending aorta and right atrium were used to institute cardiopulmonary bypass (CPB). CABG (LITA to #7, SVG to #4 PD) was performed. Arterial cannulation was then switched to the left femoral artery. The proximal aorta was cross-clamped between the left vertebral artery and the left subclavian artery under the partial CPB, and the distal aorta was occluded with a occulusive balloon catheter via the right femoral artery. The selective left axillar artery cannulation was performed to perfuse LITA. The aneurysm was resected and closed with a patch. His post-operative course was uneventful.

Strategy for Avoiding Cerebral Complications during Surgery for Arch and Distal Arch Aneurysm

Cerebral complications are devastating events associated with surgery for arch and distal arch aneurysms. We have assessed retrospectively the impact of aortic clamping, perfusion methods, and the etiology of aneurysms on the occurrence of cerebral complications during arch and distal arch operations. Thirty-two patients underwent arch and distal arch operations for aortic aneurysms or dissection from April 1990 to September 1999. The age of the patients was 62 ± 2 years, and 13 patients were female. In the early series, before 1995, among 10 patients with atherosclerotic true aneurysms who underwent aortic clamping at the transverse arch, 4 had serious cerebral complications. One patient with an infectious pseudoaneurysm who underwent patch repair of the aortic arch under deep hypothermic circulatory arrest (DHCA) with retrograde cerebral perfusion also had a fatal cerebral infarction. In the later series of the study, after 1996, we abandoned aortic clamping at the transverse arch in patients with atherosclerotic distal arch aneurysms by employing DHCA and selective cerebral perfusion (SCP). Since then we have performed 12 operations using DHCA and SCP for arch aneurysms and aortic dissection without cerebral complications. In conclusion, DHCA with SCP is a reliable technique for avoiding cerebral complications during surgery for arch and distal arch aneurysms and aortic dissection.

A Surgical Case Report of Three-Channeled Aortic Dissection of the Ascending Aorta.

今回われわれは, 38歳男性の上行大動脈三腔解離を経験した. 術前弓部分枝血管は真腔, 腹部分枝血管は偽腔から分枝していると診断した. 手術は, 右房脱血, 左大腿動脈および右腋窩動脈送血で超低体温脳分離体外循環下に弓部大動脈部分置換術を施行した. 復温中, 解離の波及による腕頭動脈の閉塞をきたした. 右腋窩動脈送血を再開し, 腕頭動脈を人工血管置換しことなきを得た. 第一解離腔が DeBakey II型, 第二解離腔が DeBakey IIIb型で逆行性解離より上行大動脈が三腔解離構造を示した.

Myonephropathic Metabolic Syndrome After Bilateral Aortoiliac Bypass: A Pathogenic Role of Cholesterol Microemboli A Case Report

A 72-year-old man was admitted to our hospital for management of intermittent claudication. A preoperative angiogram showed right common iliac artery occlusion with wellmaintained peripheral flow via collaterals and 50% stenosis of the aortic bifurcation through the left common iliac artery. The authors performed bilateral aortoiliac artery bypass surgery. Immediately following the operation, the left lower limb was cyanotic and cold despite a good pulse in the left dorsalis pedis artery. He suffered from severe pain throughout his entire left calf and part of his thigh. Thrombolytic therapy combined with anticoagulation therapy was started in an attempt to reduce limb ischemia. However, swelling of the left calf increased, and clinical and metabolic manifestations consistent with myonephropathic metabolic syndrome (MNMS) developed. Serum creatine kinase and creatinine rose to 21,600 u/L and 2.8 mg/dl, respectively. His toe became necrotic and a transmetatarsal amputation was done. A skin biopsy taken from the edge of the amputation revealed cholesterol crystals within the capillaries. This report suggests that massive cholesterol microemboli are responsible for MNMS in this patient.