Diss. (sammanfattning) Umeå : Umeå universitet, 2006. / Härtill 4 uppsatser.

Extracorporeal circulation damages blood and causes harmful side effects such as stroke and/or systemic inflammatory response in patients. Reactions of blood components to extracorporeal circulation include complement and inflammatory reactions, coagulation and thrombogenesis, frank hemolysis, and platelet activation and adhesion to the extracorporeal circuit. Non-physiologic pressure and flow produced by blood pumps contribute to blood injury. Two pump types, roller and centrifugal, are used for maintaining flow, with various models available from different manufacturers. This study compared the effects of these two pumps in identical, isolated, artificial circuits to a non-pumped control for a period of 24 hours on heparinized porcine blood. Hematology parameters were used to evaluate blood damage. Mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, platelet count, and mean platelet volume were affected by time of circulation. Mean corpuscular hemoglobin, platelet count, and red cell distribution width were different between circulated and non-circulated blood, however no differences were found between the pumping systems in any parameter. Red blood cell count, total hemoglobin, and hematocrit were not affected by time or treatment. The changes observed in this study have implications for the use of extracorporeal circulation in the clinical setting and in future use of blood as a potential organ perfusion medium. / Master of Science

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 89-94).

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23071号 / 医博第4698号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 YOUSSEFIAN Shohab, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20965号 / 医博第4311号 / 新制||医||1026(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 平井 豊博, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21263号 / 医博第4381号 / 新制||医||1029(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 福田 和彦, 教授 木村 剛 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: Heparin-induced thrombocytopenia (HIT) is an iatrogenic immune-mediated prothrombotic disorder that is a direct consequence of heparin therapy. In HIT, antibodies are generated against complexes of platelet factor-4 (PF4) and heparin. Immunoglobulin G (IgG) antibodies bind to PF4/heparin complexes and cause Fc-receptor-mediated activation of platelets and monocytes. PF4 binds endogenous heparin-like polyanions to reveal cross-reactive epitopes that can also bind anti-PF4/heparin antibodies. Based on this observation, researchers have suggested that exposure to PF4/polyanion complexes can sensitize immune cells to become activated to produce HIT antibodies following iatrogenic heparin exposure. Research objective: The objective of this study is to determine whether the preoperative PF4-dependent immune response is associated with postoperative anti-PF4/heparin antibody production in a cohort of patients undergoing cardiopulmonary bypass surgery. Materials and methods: To assess the preoperative immune response to PF4, we utilized two assays: (1) a 3H-thymidine uptake assay to measure peripheral blood mononuclear cell (PBMC) proliferation in response to in vitro stimulation with PF4 and (2) a PBMC ELISPOT assay to measure the preoperative frequency of PF4-specific antibody-secreting cells. Proliferation was quantified as a stimulation index (SI). We then utilized a PF4/heparin-dependent enzyme immunoassay to measure the in vivo levels of anti-PF4/heparin antibodies produced by these patients in the postoperative period. Results: Our findings suggest that preoperative PF4-dependent proliferation is not associated with postoperative polyspecific anti-PF4/heparin antibody production [Spearman’s ρ (95% CI) = –0.02 (–0.32, 0.28), P = 0.91]. PF4-dependent proliferation had a weak negative association with postoperative anti-PF4/heparin IgG antibody production [Spearman’s ρ (95% CI) = –0.31 (–0.56, –0.02), P = 0.04], but was not associated with postoperative IgM or IgA anti-PF4/heparin antibody production [IgM: Spearman’s ρ (95% CI) = –0.04 (–0.33, 0.26), P = 0.78; IgA: Spearman’s ρ (95% CI) = –0.05 (–0.34, 0.25), P = 0.73]. Qualitative analysis demonstrated that two patients who had the strongest preoperative PF4-dependent proliferation responses produced the highest postoperative levels of anti-PF4/heparin IgM antibodies, but this relationship was not observed with postoperative anti-PF4/heparin IgG antibodies. Moreover, the preoperative frequency of PF4-specific antibody-secreting cells (ASCs) was also not associated with postoperative levels of anti-PF4/heparin IgM or IgG antibodies [IgM: Spearman’s ρ (95% CI) = 0.30 (–0.79, 0.93), P = 0.683; IgG: Spearman’s ρ (95% CI) = –0.21 (–0.92, 0.83), P = 0.600]; however, this was only completed on five patients and so the sample size should be increased before any meaningful conclusions can be drawn. We also demonstrated that PF4-dependent proliferation increases 5–6 days following cardiopulmonary bypass surgery [geometric mean (GM) postoperative PF4 alone proliferation (in SI) vs. GM preoperative PF4 alone proliferation (in SI) ± SEM: 23.7 ± 1.3 vs. 6.9 ± 1.5, P = 0.009]. Conclusions: Based on our findings, we conclude that preoperative PF4-dependent proliferation is unable to predict postoperative anti-PF4/heparin antibody production in this cohort of cardiopulmonary bypass patients. Due to the small sample size, we are unable to make conclusive statements regarding the relationship between preoperative PF4-specific ASC frequency and postoperative anti-PF4/heparin antibody production, but our findings would suggest that an association does not exist between these two variables in this patient cohort. Cardiopulmonary bypass surgery, however, may mobilize the postoperative immune cell repertoire to become activated against the self-protein PF4 and may therefore contribute to the postoperative HIT immune response. / Thesis / Master of Science (MSc) / Background: Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that is a direct consequence of heparin therapy. In HIT, antibodies are generated against complexes of platelet factor-4 (PF4) and heparin. Antibodies bind to PF4/heparin complexes and cause activation of platelets and monocytes. Researchers have suggested that exposure to PF4/polyanion complexes can sensitize immune cells to become activated to produce HIT antibodies following iatrogenic heparin exposure. Research objective: The objective of this study is to determine whether the preoperative PF4-dependent immune response is associated with postoperative anti-PF4/heparin antibody production in a cohort of patients undergoing cardiopulmonary bypass surgery. Materials and methods: To assess the preoperative immune response to PF4, we measured cellular proliferation in response to PF4 stimulation and the preoperative frequency of PF4-specific antibody-secreting cells. We also measured the level of anti-PF4/heparin antibodies following surgery. Results: Our findings suggest that preoperative PF4-dependent proliferation is not associated with postoperative anti-PF4/heparin antibody production. Moreover, the preoperative frequency of PF4-specific antibody-secreting cells (ASCs) was also not associated with postoperative levels of anti-PF4/heparin antibodies; however, this was only completed on five patients and so the sample size should be increased before any meaningful conclusions can be drawn. We also demonstrated that proliferation increases 5–6 days following cardiopulmonary bypass surgery. Conclusions: Based on our findings, we conclude that preoperative proliferation is unable to predict postoperative anti-PF4/heparin antibody production in this cohort of patients. Due to the small sample size, we are unable to make conclusive statements regarding the relationship between preoperative ASC frequency and postoperative anti-PF4/heparin antibody production. Cardiopulmonary bypass surgery, however, may mobilize the postoperative immune cell repertoire to become activated against the self-protein PF4 and may therefore contribute to the HIT immune response.

No description available.

The design of a microcomputer-based monitoring and display system for a cardiopulmonary bypass loop is discussed. Analog signals representing blood temperature and oxygen saturation of sample points entering and leaving the blood oxygenator, patient temperature, oxygenator heat exchanger water temperature and hemoglobin content are monitored and displayed. The hemoglobin content and oxygen saturation signals, input from a reflective-type hemoglobin meter and oximeter are corrected for blood temperature and operator input pH. The oxygen saturation is also corrected for hemoglobin content. Oxygen transfer to the patient is calculated and displayed to evaluate the effectiveness of the system in cardiopulmonary support. Alarms are issued for free gas in blood, no blood flow, and high oxygenator water temperature. The hardware and software design is described along with schematics and flowcharts. A complete software listing is included. The monitoring and display system is operational, but has not been tested with flowing blood. / M.S.

Abstract Cardiac surgery with cardiopulmonary bypass (CPB) results in hemodilution, systemic inflammatory response, activation of coagulation and fibrinolysis, and microembolisation, which may all contribute to postoperative organ dysfunction. As an attempt to attenuate these side effects, the use of minimized cardiopulmonary bypass (MCPB) systems has increased. Compared to conventional CPB (CCPB), they are characterized with reduced artificial surface area and blood-air interface. The goal of these alterations has been to reduce systemic inflammation, preserve coagulation function and minimize the need for blood tranfusions. This study was aimed at determining whether or not MCPB attenuates the adverse effects of CPB. In study I, the safety, feasibility and effect on transfusion requirements of MCPB was investigated in unselected coronary artery bypass surgery (CABG) patients. In studies II and III, the incidence of retinal microembolism after CABG and aortic valve replacement (AVR) surgery with MCPB was compared to that of CCPB by means of fluorescein angiography. Furthermore, in studies II and III, the effect of MCPB on systemic inflammation, coagulation, endothelial activation and injury, as well as on platelet activity, was compared to those of CCPB. In study IV, the effect of MCPB on intestinal mucosal damage following CPB was compared to CCPB in a porcine model of prolonged CPB. MCPB appeared as safe and feasible as CCPB in unselected CABG patients (Study I). MCPB was associated with decreased retinal microembolism compared to CCPB in CABG patients (Study II). Conversely, the difference in retinal microembolism in AVR patients was not statistically significant (Study III). MCPB was associated with a decrease in neutrophil activation in CABG and AVR patients as compared to CCPB. However, there were no differences in coagulation, endothelial activation and injury, or in platelet activity (Studies II, III). There were no differences in markers of intestinal mucosal damage between MCPB and CCPB following prolonged CPB in the experimental model (Study IV). The results of this study suggest that MCPB may be used safely with CABG patients, with beneficial effects on hematocrit, and attenuated neutrophil activation. In CABG patients, MCPB is associated with reduced retinal microembolism, suggesting a decreased embolic load to the brain. The clinical feasibility of MCBP requires further technical evolution in the management of valve surgery. The results of the animal model support previous concerns regarding intestinal mucosal damage during CPB. / Tiivistelmä Sydänkeuhkokoneen käyttö aiheuttaa elimistössä hemodiluution, yleistyneen tulehdusvasteen ja hyytymisjärjestelmän aktivoitumisen sekä mikroembolisaatiota. Ilmiöt ovat yleensä lieviä ja ohimeneviä, mutta voivat johtaa elintoimintahäiriöihin ja pitkittyneeseen toipumiseen sydänleikkauksen jälkeen. Haittojen lievittämiseksi sydänkeuhkokonetta on pyritty kehittämään fysiologisemmaksi. Miniperfuusiolaitteistoissa kiertävän veren kontakti pintamateriaalien ja ilman kanssa jää pienemmäksi ja veren laimenemista tapahtuu vähemmän. Tutkimuksen tavoitteena oli selvittää voidaanko miniperfuusiolla lievittää sydänkeuhkokoneen haittoja. Ensimmäisessä osatyössä selvitettiin miniperfuusion käyttökelpoisuutta ja vaikutusta verensiirtotarpeeseen ohitusleikkauspotilailla valikoimattomassa aineistossa. Toisessa ja kolmannessa osatyössä selvitettiin silmänpohjan mikroembolioiden ilmaantuvuutta miniperfuusion ja perinteisen sydänkeuhkokoneen käytön jälkeen ohitusleikkauspotilailla ja aorttaläppäleikkauspotilailla. Toisessa ja kolmannessa osatyössä selvitettiin lisäksi miniperfuusion vaikutuksia yleistyneen tulehdusvasteen voimakkuuteen, hyytymisjärjestelmään sekä endoteelin aktivaatioon perinteiseen sydänkeuhkokoneeseen verrattuna. Neljännessä osatyössä verrattiin kokeellisessa mallissa miniperfuusion ja perinteisen sydänkeuhkokoneen vaikutuksia suoliston limakalvon eheyteen. Miniperfuusio ilmeni yhtä käyttökelpoiseksi kuin perinteinen sydänkeuhkokone ohitusleikkauspotilaiden hoidossa. Ohitusleikkauspotilailla ilmeni vähemmän silmänpohjan mikroembolioita miniperfuusion jälkeen, mutta aorttaläppäleikkauspotilailla ero ei ollut tilastollisesti merkitsevä. Miniperfuusion käyttöön liittyi vähemmän neutrofiilien aktivaatiota. Tekniikoiden välillä ei ilmennyt eroa hyytymisjärjestelmän eikä endoteelin aktivaatiota osoittavissa merkkiaineissa. Sydänkeuhkokoneen käyttö aiheutti saman tasoisen suoliston limakalvon vaurion miniperfuusiolla ja perinteisellä sydänkeuhkokoneella. Tutkimuksen perusteella miniperfuusiotekniikkaa voidaan käyttää turvallisesti ohitusleikkauspotilaiden hoidossa ja sen käyttö vähentää hemodiluutiota ja neutrofiilien aktivaatiota verrattuna perinteiseen sydänkeuhkokoneeseen. Miniperfuusiolla voidaan vähentää sydänkeuhkokoneen käytön aiheuttamaa silmänpohjan mikroembolisaatiota, joka saattaa viitata vähäisempään aivoverenkierron mikroembolisaatioon. Miniperfuusiotekniikoiden tulee edelleen kehittyä hyödyttämään enemmän myös aorttaläppäleikkauspotilaita. Löydökset koskien sydänkeuhkokoneen aiheuttamia suoliston limakalvovaurioita vahvistavat aiempaa olettamusta suoliston haavoittuvuudesta sydänleikkauksen jälkeen.