Hiroyuki Orita

Differential secretion of plasminogen activator activity by postsurgical activated macrophages

Macrophage functions during postsurgical tissue repair include secretion of neutral proteases like plasminogen activator. Accordingly, we studied the differential secretion of plasminogen activator by postsurgical macrophages. Rabbits underwent resection and reanastomosis of their small bowel (three rabbits/time group). Postoperatively (up to 28 days), they underwent a second laparotomy for collection of ascites cells by lavage. Cells were incubated with culture medium containing 10% acid-treated fetal calf serum. After 2 days, the medium was removed (1-2 days media, M1) and replaced for 2 more days (3-4 days media, M2). Plasminogen activator activity of the medium (M1 and M2) was determined using a modified indirect solid-phase radioassay. The specific plasminogen activator activity (plasminogen-dependent-plasminogen-independent activator activity) in M1 was 43 mPU/10(6) cells in nonsurgical control rabbits. Exudative cells on Day 1 had less activity than control, and by Day 5, the activity significantly increased to 290% of control levels, reaching peak value on Day 14 (360%). The specific plasminogen activator activity in M2 was 310 mPU/10(6) cells in nonsurgical control media. Exudative cells on Day 1 had less activity than control, while, on Days 3-7, they were the same as control. By day 10, specific activity significantly increased to peak levels 188% of control and then gradually decreased. Since a marked increase in the number of macrophages parallels the increase in these metabolic activities through postsurgical Day 10, postsurgical activated macrophages appear to play an important role in peritoneal healing.

Modulation of proline and glucosamine incorporation into tissue repair cells by peritoneal macrophages

The purpose of this study was to determine the patterns of [14C]proline and [14C]glucosamine incorporation by tissue repair cells (TRC) as modulated by postsurgical macrophages. Rabbits underwent a midline laparotomy followed by resection (2.0 cm) and reanastomosis of their ileum. Another group of rabbits underwent peritoneal wall abrasion with sterile gauze until punctate bleeding developed. Postoperative (1-28 days) exudate cells (PEC) were recovered from the peritoneal cavity after reanastomosis, and (TRC) were obtained directly from the injured peritoneal surface after abrasion. Since the postsurgical exudate was composed mainly of macrophages, we examined the effect of postsurgical macrophage-spent media on the incorporation of [14C]proline, [14C]glucosamine, and [3H]thymidine by TRC. After 7 days of culture, Postsurgical Day 7 TRC were incubated with spent media from postsurgical PEC (greater than 90% macrophages). When TRC were cultured with macrophage-spent media, the number of TRC increased significantly compared to that of fresh medium-treated controls. The incorporation of [3H]thymidine by TRC was also enhanced by macrophage-spent media. The incorporation of [14C]proline and [14C]glucosamine by TRC was also enhanced when incubated with macrophage-spent medium. However, when data were expressed on a per cell basis, incorporation of [14C]proline and [14C]glucosamine by TRC cultured with macrophage-spent media was the same or less than that by cells incubated with fresh medium. These data suggest that the increase in incorporation of glucosamine and proline into connective tissue protein by postsurgical repair cells may be directly modulated by macrophages recruited in response to surgical injury and that this increase is due to the fibroproliferative effect of postsurgical macrophages.

Modulation of fibroblast proliferation and transformation by activated macrophages during postoperative peritoneal reepithelialization

We studied the modulation of fibroblast proliferation and transformation by postoperative macrophages. One group of rabbits underwent resection and reanastomosis of the small bowel, after which macrophages were collected by peritoneal lavage. A second group of rabbits underwent peritoneal wall abrasion followed by collection of local fibroblast on postoperative days 4 and 8. Postoperative macrophages were added to five culture dishes containing fibroblasts. After 24 hours, tritiated thymidine was added to the culture dishes and incubated overnight. In two other dishes, which were incubated for up to 8 days, a 24-hour pulse of tritiated thymidine was added before culture termination. Postoperative day 4 fibroblasts demonstrated a greater increase in cell number during the culture interval compared to fibroblasts collected on postoperative day 8. By the second day of coculture with macrophages collected from different postoperative days, tritiated thymidine incorporation by day 4 fibroblasts was suppressed, especially by postoperative day 7 macrophages. Thereafter, a stimulation in tritiated thymidine uptake was found. In contrast, tritiated thymidine uptake by day 8 fibroblasts was accelerated by coculture with macrophages, especially those collected on postoperative day 7. Day 4 fibroblasts assumed a more spindly appearance when cocultured with macrophages than did day 8 fibroblasts. Taken together, these data suggest that macrophages activated in response to surgical injury may secrete substances that induce proliferation and transformation of fibroblasts.

Intramuscular hemangioma in the right ventricle.

Intramuscular cardiac hemangiomas are extremely rare. We describe a 74-year-old man with a tumor occupying the apex of the right ventricle that was incidentally diagnosed by echocardiography. Computed tomography and coronary angiography showed that the tumor arose from the ventricular septum and that the feeding artery was a branch of the right coronary artery. The tumor was completely excised, and the postoperative course was uneventful. Histological examination revealed that the tumor was a cardiac hemangioma (intramuscular type). To our knowledge, this is only the second case report of an intramuscular cardiac hemangioma in the world literature.

Association of Serum Uric Acid Levels with Leg Ischemia in Patients with Peripheral Arterial Disease after Treatment

Aim: We investigated the relationships of serum uric acid levels with the progression of atherosclerosis in patients with peripheral arterial disease (PAD) after treatment. Methods: Subjects were male patients diagnosed with PAD. Atherosclerosis at the common carotid artery was evaluated based on its intima-media thickness (IMT). Leg arterial flow was evaluated by measuring ankle-brachial index (ABI) and exercise-induced decrease in ABI. Results: Among various risk factors including age, blood pressure, adiposity, estimated glomerular filtration rate, and blood lipid, blood glucose, uric acid, fibrinogen and C-reactive protein levels, only uric acid levels showed significant correlations with ABI [Pearsons correlation coefficient, −0.292 (p < 0.01)] and leg exercise-induced decrease in ABI [Pearsons correlation coefficient, 0.236 (p < 0.05)]. However, there was no significant correlation between uric acid levels and maximum or mean IMT. Odds ratios of subjects with the 3rd tertile versus subjects with the 1st tertile for uric acid levels were significantly higher than the reference level of 1.00 for low ABI [4.44 (95% confidence interval, 1.45–13.65, p < 0.01)] and for high % decrease in ABI after exercise [4.31 (95% confidence interval, 1.34–13.82, p < 0.05)]. The associations of uric acid levels with the indicators of leg ischemia were also found after adjustment for age, history of revascularization therapy, diabetes, smoking, alcohol consumption, body mass index, triglyceride levels, and renal function. Conclusion: Uric acid levels are associated with the degree of leg ischemia in patients with PAD. Further interventional studies are needed to determine whether the correction of uric acid levels is effective in preventing the progression of PAD.

Recent Knowledge of Smoking and Peripheral Arterial Disease in Lower Extremities

Peripheral arterial disease (PAD) is an atherosclerotic obstructive disease of the arteries in lower extremities. Patients with PAD show high rates of mortality from coronary artery disease (CAD) and stroke. Smoking as well as diabetes is an important risk factor for PAD. A lesion of PAD in the lower extremities tends to be more proximal in smokers than in nonsmokers and to be more distal in patients with diabetes than in nondiabetics. By a systematic review, the odds ratio for PAD of smokers vs nonsmokers has been reported to be in the range of 1.7-7.4. Previous epidemiological studies suggest a stronger association of smoking with PAD than that with CAD. Nitric oxide (NO) is an important molecule suppressing the progression of atherosclerosis, but this function is compromised by smoking. Smoking decreases the bioactivity of NO and the expression level of NO synthase. In addition, smoking results in deteriorations of risk factors for atherosclerosis such as decreases in blood HDL (high-density lipoprotein) cholesterol and tissue plasminogen activator levels and increases in the levels of blood triglycerides, LDL (low-density lipoprotein) cholesterol, fibrinogen and the von Willebrand factor. Thus, smoking increases blood coagulability and deteriorates the blood lipid profile, resulting in thrombogenetic proneness and dyslipidemia. Smoking also increases the generation of atherogenic oxidized LDL in blood and decreases antiatherogenic prostacyclin production in the vascular endothelium. Smoking cessation is important for the prevention and therapy of PAD, and to this end, counseling by physicians and nicotine replacement therapy are useful and strongly recommended for patients with PAD.

Clinical Status of the Late Stage after Valvulectomy without Prosthetic Replacement.

活動期感染性心内膜炎に対し, 右心系の弁切除非置換術を施行した3例の術後遠隔期を報告した. 肺動脈弁全切除を施行した1例と三尖弁部分切除を施行した1例では安定した状態にあったが, 三尖弁全切除を施行した1例では, 進行性の右心系の拡大を認めた. 三尖弁位の逆流による右心の容量負荷の増大によるものと思われた. 右心系の弁置換術の遠隔の遠隔成績に問題が残る現在, 三尖弁では可及的に遺残組織による弁形成術か, パッチによる弁再建術を行うことが望ましいと考えられた.