Ryuji Kunitomo

Macrophage-Derived Angiopoietin-Like Protein 2 Accelerates Development of Abdominal Aortic Aneurysm

Objective—Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). Methods and Results—Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl2-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. Conclusion—Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.

The effects of cardiopulmonary bypass on postoperative oxygen metabolism

The relationships between oxygen delivery (DO2), oxygen consumption (VO2), and the extraction rate (ER=VO2/DO2x100) in patients undergoing cardiopulmonary bypass (CPB) may differ from the normal physiologic state due to the oxygen debt acquired during CPB. Blood gas analysis and hemodynamic parameters were repeatedly measured for the determination of DO2 and VO2 in 40 patients undergoing CPB, every 8h during the first 48h postoperatively. As a control, 20 patients who had suffered acute myocardial infarction (AMI) were also studied using the same protocol. In the CPB group, a regression analysis showed that VO2 was significantly dependent on DO2, even within the physiologic range of DO2 (>500 ml/min per m2); VO2=121.4+0.0844×DO2 (r=0.254,P=0.023). Conversely, in the AMI group, no such supply-dependent consumption was observed within the same range of DO2. At an ER of 30%, which is the optimal value in general, the DO2 of the CPB group was 575 ml/min per m2 and that of the AMI group was 493 ml/min per m2. All these results suggest that patients undergoing CPB need a much higher oxygen supply to recover from the oxygen debt acquired during open heart surgery.

Altered plasma antigen levels of tissue factor pathway inhibitor during open-heart surgery

r = 0.96, P < 0.0001) which increased significantly after heparin injection (P < 0.0001), and increased further during the bypass period (P < 0.005). The increased free TFPI antigen level during CPB correlated with the duration of bypass (r = 0.65, P = 0.02). When heparin was neutralized by protamine, the free TFPI antigen level decreased immediately, but remained higher than the preoperative level (P < 0.005). These results suggest that plasma TFPI antigen levels increase during CPB.

Monocyte chemotactic S19 ribosomal protein dimer in atherosclerotic vascular lesion

To elucidate the molecular mechanism inducing monocyte/macrophage infiltration in the atherosclerotic lesion, we measured the monocyte chemotactic capacity in the extracts of aortic lesions. Five out of seven extracts exhibited significant chemotactic activities. Immunohistochemical examination with an anti-CD68 monoclonal antibody demonstrated that the five positive lesions possessed obvious monocyte/macrophage infiltrations at the intima, whereas the two negative lesions did so at significantly lower intensities. We subjected the chemotactic extracts to immunological analyses to identify the monocyte chemoattractant in them. The monocyte chemotactic capacities of all positive extracts were removed with anti-S19 ribosomal protein (RP S19) antibody beads and antimonocyte chemoattractant protein-1 (MCP-1) antibody beads. In three of the five extracts, the anti-RP S19 antibody beads were more effective than the anti-MCP-1 antibody beads for removal, while in the remaining two extracts, the opposite was observed. A combined immunoabsorption with these beads depleted the monocyte chemotactic capacity of a representative sample of each group. Consistently, the chemotactic capacity of an apparently RP S19 dimer-predominant extract was strongly inhibited by the presence of a C5a receptor antagonist. These results suggest that the RP S19 dimer and MCP-1 play a major role in the monocyte/macrophage infiltration of the atherosclerotic vascular lesion.

Thoracoabdominal aortic aneurysm combined with aortic occlusion.

The case of a 73-year-old woman with aneurysms of the thoracoabdominal aorta and distal arch, combined with aortic occlusion, is reported. Cannulation from the femoral artery was not possible because of the aortic occlusion. Blood supply to the abdominal viscera and lower extremities was achieved only by selective perfusion from the celiac artery, superior mesenteric artery, and bilateral renal arteries. A unique choice of selective perfusion for distal circulatory support is described.

Intravascular papillary endothelial hyperplasia in an aneurysm of the superficial temporal artery: Report of a case

We herein report a rare case of an intravascular papillary endothelial hyperplasia in an aneurysm of the superficial temporal artery. The patient was a 67-yearold Japanese woman. She noticed a throbbing swelling in her left forehead, which had gradually been increasing in size. She had no previous history of head trauma. Ultrasonography and three-dimensional computed tomographic angiography revealed an aneurysm with a mural thrombus measuring 10 mm in diameter fed by the frontal branch of the left superficial temporal artery. The aneurysm of the superficial temporal artery was dissected from the surrounding tissues, and was resected after ligation of feeding vessels. A microscopic examination revealed papillary endothelial hyperplasia in a true aneurysm. Nontraumatic aneurysms of the superficial temporal artery are rare. In the previous English literature, there have only been a few reports of papillary endothelial hyperplasia in an artery, and none in an aneurysm of the superficial temporal artery.

Anticoagulant effects of argatroban on the pre-DIC state in patients with an aortic aneurysm: A comparative study of heparin

We compared the efficacy of argatroban, a new synthetic thrombin-specific inhibitor, with that of heparin in pre-DIC state patients with abdominal aortic aneurysm (AAA). A pre-DIC state was diagnosed by a detection of soluble fibrin monomer complex (FM) and increased levels of thrombin-antithrombin III complex (TAT) of more than 20 ng/ml. Twelve patients showing a pre-DIC condition were treated with argatroban (40 mg/day, n=6) or heparin (10,000 U/day, n=6) for 5 days. Coagulation and fibrinolytic profiles were analyzed before and after drug administration. FM became negative in two (33%) patients after the argatroban treatment and in all (100%) of the heparin-treated patients. Plasma levels of TAT were significantly decreased after the heparin treatment, however, there was no significant alteration in this parameter after the argatroban treatment. In conclusion, the anticoagulant effects of heparin were superior to those of argatroban in controlling the pre-DIC state associated with AAA.

Cardiac hemangioma of the right ventricle —Report of a case—

A 74-year-old male was admitted to our hospital with a diagnosis of intra-cardiac tumor on echochardiography, CT, and MRI. The tumor was located on the free wall of the right ventricle and protruded into the outflow tract. The surgical excision of the tumor was performed under cardiopulmonary bypass. The size of the tumor was 5 x 5 x 4 cm. Histological examination disclosed cavenous hemangioma. The post opertive course was uneventful. This is the forth case reported in Japan and the fifteenth case in the world.

A simple method of intraoperative preparation of a stent graft for distal aortic arch aneurysm

J Thorac Cardiovasc Surg Takaji, Yukihiro Katayama and Michio Kawasuji Ryuji Kunitomo, Shigeyuki Tsurusaki, Hisashi Sakaguchi, Ichiro Ideta, Kentaro arch aneurysm A simple method of intraoperative preparation of a stent graft for distal aortic http://jtcs.ctsnetjournals.org/cgi/content/full/125/6/1535 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Coronary artery bypass grafting using a bifurcating radial artery

A 61-year-old man with angina pectoris was admitted for elective coronary artery bypass grafting. The left anterior descending artery, and the two posterolateral branches (PLA1 and PLA2) of the circumflex artery required bypass grafting. At operation, the distal portion of the left radial artery was found to bifurcate, both branches having an equal size. We decided to use the bifurcating radial artery as a conduit for bypass grafting to the branches of the left circumflex artery. One distal end of the radial artery was subsequently anastomosed to the PLA1 branch and the other distal end was anastomosed to PLA2. Postoperative coronary angiography showed both branches of the radial artery to have good patency.