Analysis of Reactive Oxygen Metabolites (ROMs) after Cardiovascular Surgery as a Marker of Oxidative Stress

The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress

Prediction of extreme wind speed and wave height by using numerical simulation

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 石原 孟, 東京大学教授 田島 芳満, 東京大学教授 大岡 龍三, 東京大学准教授 知花 武佳, 東京大学特任講師 山口 敦University of Tokyo(東京大学

Preoperative oral administration of pentoxifylline ameliorates respiratory index after cardiopulmonary bypass through decreased production of IL-6

Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead to considerable post-operative mortality. Recently, pentoxifylline (PTX), a methylxanthine derivative, has been reported to be effective in inhibiting proinflammatory cytokine production. This study aimed to determine whether or not PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in patients undergoing cardiovascular surgery. Thirty adult patients were randomly separated into 2 experimental groups and 1 control group of 10 patients each. The experimental group received peroral PTX administration (Group 1: 600 mg/day, Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2, PTX administration was started on preoperative day 5 and continued for 5 days. Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on postoperative day 1 were also determined. There were no significant differences in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2 were significantly decreased compared with those in Group 1 and the control group. These results, therefore, suggested that preoperative daily administration of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a beneficial effect on the postoperative course after cardiovascular surgery.</p

Beneficial effect of EPC-K1 on the survival of warm ischemic damaged graft in rat cardiac transplantation.

A newly introduced compound, EPC-K1, represents a phosphate diester linkage of vitamin E and vitamin C. The effect of EPC-K1 on the reperfusion injury was evaluated in a heterotopic cardiac transplantation model using syngenic combination rats. Prior to the warm ischemia, 12mg EPC-K1/kg was administered intravenously to donor rats. After 15 min of warm ischemic time, hearts were harvested and perfused with 4 degrees C saline. After completion of the transplantation, recipient rats were also treated with intravenous 12 mg EPC-K1/kg, before reperfusion. Saline was used instead of EPC-K1 for both donors and recipients in the control group. On the 7th post-transplantation day, graft survival was 7 out of 8 in EPC-K1 group, versus 1 out of 9 in the control group (p &#60; 0.001). Thiobarbituric acid-reactive substance levels in the recipient serum, three hours after reperfusion, were significantly limited, in the group in which EPC-K1 was administered only to donors. But it was not possible to clarify whether the effect of EPC-K1 is primarily at the donor or recipient levels at this time. These results indicate that EPC-K1 may reduce reperfusion injury after cardiac transplantation. This beneficial effect may be mediated by the hydroxyl radical scavenging properties of EPC-K1.</p

Influence of Hemofiltration on Intradialytic Plasma Volume Decrease

Background/Aims: Compared with hemodialysis (HD), hemodiafiltration (HDF) reduces the frequency of episodes of intradialytic hypotension. Intradialytic plasma volume decrease (IPVD) induced by ultrafiltration is a leading cause of the episodes, and hemofiltration might have a preventive effect on IPVD. This study examined whether online HDF (ol-HDF) prevented IPVD compared with HD. Methods: Online HDF of pre-dilution mode (pre-ol-HDF) and post-dilution mode (post-ol-HDF) and HD were performed in 22 patients on maintenance dialysis. In each session, IPVD was calculated by using an intradialytic change in hematocrit, and IPVD in pre-ol-HDF and post-ol-HDF was compared with that in HD in a crossover manner. Results: While the ratios of intradialytic body weight loss to post-dialysis BW (IBWL/BW) in ol-HDF were generally smaller than those in HD, the levels of IPVD and IPVD/IBWL/BW were generally larger than those in HD; the IPVD levels were 0.108 ± 0.058, 0.113 ± 0.053, and 0.101 ± 0.057 (P = 0.67), and those of IPVD/IWL/BW were 2.21 ± 0.97, 2.32 ± 0.91, and 1.98 ± 1.14 (P = 0.21) in pre-ol-HDF, post-ol-HDF, and HD, respectively. Conclusion: Online mode hemofiltration, in either pre-dilution mode or post-dilution mode, performed in combination with hemodialysis has no preventive effect on IPVD

自己血小板貯血における採血前ヘパリン投与が採取血小板の凝集能に及ぼす影響に関する検討

心臓大血管の手術において術中止血に難渋する場合や大量輸血を要する場合がある.特に血小板製剤は供給量が限られており,自己血貯血,血小板成分貯血の有用性が報告されている.術中自己血小板採取には約90分を要するが,ヘパリンの採取血小板機能への影響は不明であり,採取終了まで人工心肺を開始できないことから,手術時間が延長しているのが現状である.ヘパリンによる自己多血小板血漿(PRP)への影響がなければ,採取と同時に手術の進行が可能となり,手術時間の短縮が期待できる.今回我々は,全身麻酔下にブタを用いて,成分採血装置COMPONENT COLLECTION SYSTEM(HAEMONETICS社)による自己血小板採取を行い,ヘパリンがPRPの血小板凝集能に与える影響を検討した.1頭のブタに対し1週間の間隔を置いて2度の採血を行い,1度目はヘパリン非投与群(N群)とヘパリン投与群(H1群)の採血を行い,2度目はヘパリン投与群のみ(H2群)採血を行った.N群とH群で採取した血小板数および血小板凝集能の比較を行った.血小板凝集能はHEMA TRACER 712(MCM社)にて測定した.本研究は川崎医科大学動物実験委員会の承認を得て行った.データ数はN群7例,H群12例(H1群7例,H2群5例)であった.PRP中の血小板数はN群で153.6±67.6×10^4 /μl,H群で142.8±47.6×104 /μlであり,有意差はなかった(p=0.6857).また,血小板の最大凝集率はN群,H群で凝集惹起物質濃度がADP2μMで32.1±9.2,24.1±13.6%(p=0.183),ADP4μMで44.6±6.4,33.5±13.3%(p=0.057),Collagen2μg/mlで43.4±28.5,28.8±16.4%(p=0.176)と有意差は認めなかったが,高濃度のADPの場合のみH群でより低い傾向にあった.今回の実験ではヘパリン投与前後で採取した自己血小板の凝集能に差は認めず,PRP中の血小板数および血小板機能はヘパリンの影響は受けないと結論できる.よって,今後は臨床での術中自己血小板採取の有用性について研究を進めていく.Homologous platelet-rich plasma (HPRP) is used during cardiovascular surgery. A shortage of homologous HPRP has been highlighted recently, and autologous platelet-rich plasma (APRP) is an alternative. It takes approximately 90 min before heparin administration to collect APRP during surgery, so this procedure delays surgical treatment. Collection of APRP after systemic heparinization (SH) could be beneficial for surgical procedures. We clarified the impact of SH on the function of collected autologous platelets. The study protocol was approved by the Animal Experiment Committee of Kawasaki Medical School (Kurashiki, Japan). We undertook collection of APRP using a COMPONENT COLLECTION SYSTEM (Haemonetics, Braintree, MA, USA) in pigs under general anesthesia. We examined the influence of heparin upon the ability of APRP to aggregate platelets. Blood collection was conducted twice from each pig at an interval of 1 week. First, we collected APRP before SH (N group), followed by sequential collection after SH (H1 group). One week after the first experiment, collection of APRP was made only after SH (H2 group). Capacity for platelet aggregation was measured using HEMA TRACER^[○!R] 712 (MCM, Tokyo, Japan) and compared between the N group and H group. Collected data were seven in the N group and twelve in the H group from six pigs. Platelet count of APRP (×104/μl) was 153.6±67.6 in the N group and 142.8±47.6 in the H group, and the difference was not significant (p=0.6857). Maximum platelet aggregation in the N group and H group was 32.1±9.2 and 24.1± 13.6% (p=0.183) in adenosine diphosphate (ADP;2μM), 44.6±6.4 and 33.5±13.3% (p=0.057) in ADP (4μM) and 43.4±28.5 and 28.8±16.4% (p=0.176) in collagen (2μg/ml). Capacity of APRP to aggregate platelets was lower in the H group compared with that in the N group, but not significantly lower. We conclude that SH does not affect the platelet count and capacity for platelet aggregation of APRP. These promising results could lead to clinical application of APRP after SH