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Biomedical subjects

J Vaage

Publications and source records attributed to J Vaage.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass.

BACKGROUND: An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS: Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS: Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS: Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.

Aged↗
PubMed2000

Unstable angina activates myocardial heat shock protein 72, endothelial nitric oxide synthase, and transcription factors NFkappaB and AP-1.

OBJECTIVE: Unstable angina may improve the clinical outcome of acute myocardial infarction, but increases the morbidity and mortality of open heart surgery. We hypothetized that unstable angina influences the myocardium, and investigated the expression of the inducible heat shock protein 72 (HSP72), constitutive HSP73, and endothelial nitric oxide synthase (eNOS), and activation of the transcription factors NFkappaB and AP-1 in cardiac tissue. METHODS: Biopsies were taken from the right atrium of 15 patients with unstable and 15 with stable angina undergoing coronary artery bypass grafting. Immunoblotting with monoclonal antibodies against HSP72, HSP73, and eNOS were performed on protein extracts, while nuclear proteins were assessed by electromobility shift assay. RESULTS: When calculating the optical density of the bands, patients with unstable angina had more than twice as much HSP72 and eNOS as stable patients (P<0.005), while HSP73 was similar in both groups. Nuclear translocation of NFkappaB and AP-1 was found in patients with anginal pain shortly before surgery, but not in stable patients or in patients without symptoms for 4 days or more prior to surgery. CONCLUSIONS: HSP72 and eNOS, which may be associated with cardioprotection in ischemic preconditioning, are increased in atrial tissue of patients with unstable angina. Activation of NFkappaB and AP-1, which regulate a battery of inflammatory genes, was found in hearts of unstable patients. NFkappaB activation may induce a myocardial proinflammatory state, possibly making the unstable myocardium more susceptible to the inflammation induced by open heart surgery.

Aged↗
PubMed2000

Pretreatment with methylprednisolone protects the isolated rat heart against ischaemic and oxidative damage.

Methylprednisolone (MP), a synthetic glucocorticoid, is widely used clinically and experimentally as acute antiinflammatory treatment. The molecular actions of MP indicate that pretreatment with this drug may be cardioprotective. We investigated if giving rats MP prior to excising their hearts for Langendorff-perfusion protected cardiac function against oxidative stress, and if this was mediated by increasing antioxidant defence or influencing myocardial nitric oxide synthase (NOS). Rats (n=6-11 in each group) were injected with MP (40mg/kg i.m.) or vehicle 24 and 12 h before Langendorff-perfusion with 30 min global ischaemia and 60 min reperfusion, or 10 min perfusion with 180 micromol/L hydrogen peroxide. Other hearts were exposed to 30 min global ischaemia 5 days after MP-injection. Additional hearts were sampled before, during, and after ischaemia for analyzing tissue activity of antioxidant enzymes. Tissue endothelial and inducible NOS (eNOS and iNOS) were investigated by immunoblotting and semiquantitative RT-PCR in a time-course after MP injection. Pretreatment with MP improved left ventricular function and increased coronary flow during postischaemic reperfusion, and this effect was sustained 5 days afterwards. When exposing hearts to hydrogen peroxide, MP improved coronary flow. Catalase, glutathione peroxidase, and oxidized glutathione were increased during reperfusion of MP-treated hearts compared to vehicle only. MP did not influence eNOS at protein or mRNA level. iNOS could not be detected by immunoblotting, indicating low cardiac enzyme content. Its mRNA initially increased the first hour after injection, thereafter decreased. In conclusions, pretreating rats with MP protects the heart against ischaemia-reperfusion dysfunction. This effect could be due to increase of tissue antioxidant activity during reperfusion. MP did not influence cardiac eNOS. mRNA for iNOS was influenced by MP, but the corresponding protein could not be detected.

Animals↗
PubMed2000

Neurologic injury in cardiac surgery: aortic atherosclerosis emerges as the single most important risk factor.

With older and sicker patients undergoing cardiac surgery, neurologic injury has emerged as an increasingly important cause of rising costs, morbidity and mortality. Several studies investigating the relationship between atherosclerotic aortic disease and subsequent adverse clinical outcomes have demonstrated that the single most important risk factor for neurologic injury following cardiac surgery is the presence of aortic atheromatous disease. The results of these studies suggest that atheroemboli are correlated with neurologic injury following cardiac surgery. Surgical techniques to avoid and prevent particulate debris during cardiac surgery may be a major step in preventing severe neurologic injury.

Aortic Diseases↗
PubMed2000

Effects of cardiac surgery on some clinically used inflammation markers and procalcitonin.

One hundred and ten patients were investigated prospectively in a study aimed at creating reference curves for inflammation markers (serum C-reactive protein (CRP), blood leukocyte count, iron, transthyretin and procalcitonin). Blood samples were taken daily and the patients were monitored for signs of infection. Ninety-six patients had no postoperative infections. CRP and leukocyte counts peaked on the third and second postoperative days, respectively. Neither patients operated on off-pump (n = 4) nor patients with minor infections (n = 11) differed from the non-infected group. Two out of three patients with major postoperative infection exhibited a secondary peak in CRP and leukocyte count. Iron and transthyretin decreased initially, followed by a slow increase without any difference between the groups. Procalcitonin was high in some non-infected patients and low in some infected patients. CRP and leukocyte count had a predictable course with a secondary peak in major infections but the other markers did not provide any valuable information.

Adult↗
PubMed2000

Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72.

Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.

Animals↗
PubMed1999

Therapy of a xenografted human colonic carcinoma using cisplatin or doxorubicin encapsulated in long-circulating pegylated stealth liposomes.

We compared the therapeutic effects of low doses of cisplatin and doxorubicin hydrochloride encapsulated in long-circulating liposomes composed of cholesterol/hydrogenated soy phosphatidylcholine-polyethylene glycol-distearoyl-phosphatidyl-ethanolamine. The encapsulation of cisplatin and doxorubicin in these liposomes made ineffectively low doses of the free drugs able to inhibit the growth of and affect cures of a human colonic carcinoma growing in nude mice. Liposome-encapsulated cisplatin had minor systemic toxic side effects indicated by an average 9% weight loss which was recovered 3-4 weeks after the last treatment. Toxicity was not observed in mice treated with liposome-encapsulated doxorubicin.

Animals↗
PubMed1999

Release of S100B during coronary artery bypass grafting is reduced by off-pump surgery.

BACKGROUND: S100B, a plasma marker of brain injury, was compared after coronary artery bypass grafting with and without cardiopulmonary bypass (CPB). METHODS: Fourteen patients with off-pump operations and 18 patients with CPB were compared. Seven patients in the off-pump group underwent a minithoracotomy and received only an arterial graft, whereas 7 patients underwent sternotomy and received both an arterial and one or two vein grafts. S100B was measured in arterial plasma using an immunoassay with enhanced sensitivity. RESULTS: S100B before the operation was 0.03 microg/L. At wound closure, S100B in patients of the off-pump and CPB groups reached a maximum level of 0.22 +/- 0.07 and 2.4 +/- 1.5 microg/L, respectively (p < 0.001). No strokes occurred. Patients without CPB receiving arterial and vein grafts released slightly more S100B (p < 0.05) than patients with only arterial grafting. In patients undergoing CPB, S100B increased slightly before aortic cannulation (p < 0.001), to the same level as the maximum reached for the non-CPB group. CONCLUSIONS: Coronary artery bypass grafting with CPB caused a 10-fold greater increase in S100B than off-pump grafting. S100B release after off-pump sternotomy with vein grafting was slightly greater than in arterial grafting through a minithoracotomy.

Aged↗
PubMed1999

Computed tomography of the sternum and mediastinum after median sternotomy.

BACKGROUND: Computed tomography is used in our hospital to diagnose complications after median sternotomy, but its efficiency is unknown. Nor is the computed tomographic appearance of normal healing of a median sternotomy known. Computed tomography was evaluated for its ability to diagnose mediastinitis and sternal dehiscence, and a reference material of normally healing median sternotomies was created. METHODS: In a prospective study, 20 patients with a normally healing median sternotomy were examined 1 week, 1 month, 3 months, and 6 months after operation. In a retrospective study, 87 scans from 65 patients that were made because a postoperative complication was suspected were reviewed. RESULTS: In the prospective study, all patients had clinically uneventful healing. None of the computed tomographic scans showed radiologic signs of healing at 3 months. At 6 months, half of the patients had healed completely. In the retrospective study, 49 scans were performed on suspicion of infection; 7 of them indicated mediastinitis, 2 were false-positive, while mediastinitis was present in a total of 16 of the scans. Thirty-eight scans were made because of sternal pain or suspected dehiscence; after 21 of the scans, recovery was uneventful, and in 11, the definite diagnosis was dehiscence or pseudarthrosis. CONCLUSIONS: Clinical healing of the sternotomy does not correlate with the computed tomographic image. Computed tomography is not a sensitive tool for diagnosing mediastinitis, and in patients with sternal pain, it adds little information.

Adult↗
PubMed1999

Warm or cold continuous blood cardioplegia provides similar myocardial protection.

BACKGROUND: This study was performed to investigate the effect of temperature of blood cardioplegia on the recovery of postischemic cardiac function. METHODS: Pigs on cardiopulmonary bypass were subjected to global ischemia (30 minutes), followed by cold (n = 10) or warm (n = 11) continuous antegrade blood cardioplegia (45 minutes) delivered at 55-60 mm Hg. RESULTS: Global left ventricular function, evaluated by preload recruitable stroke work, decreased with cold cardioplegia from 91 (85-103) [mean (quartile interval)], at baseline, to 73 (55-87) erg x 10(3)/mL postbypass (p = 0.03), but was unchanged after warm cardioplegia; 110 (80-132) to 109 (71-175) erg x 10(3)/mL (p > 0.5). However, the difference between treatment effects was not significant (p = 0.25). Diastolic function, evaluated by end-diastolic pressure-volume relation, deteriorated without any difference between groups. Mean cardioplegic flow was similar between groups. Coronary vascular resistance increased at constant rate during warm cardioplegic delivery, but remained unchanged with cold cardioplegia (p = 0.001 between regression coefficients). CONCLUSIONS: No significant difference was found in postischemic functional recovery comparing cold and warm continuous blood cardioplegia. Cold cardioplegia is therefore preferred due to added safety of hypothermia.

Animals↗
PubMed1999

Hydrogen peroxide induces endothelial cell atypia and cytoskeleton depolymerization.

Reactive oxygen intermediates induce cell injury in a variety of pathophysiological conditions. Human umbilical cord vein endothelial cell (HUVEC) cultures were exposed to 1 or 200 microM H2O2 for 15 min, and observed after 15 min, or 1, 4, 24, or 120 h. Factor VIII and the cytoskeletal proteins vimentin and tubulin were visualized immunocytochemically. Release of lactate dehydrogenase (indices of cell membrane injury) did not increase after H2O2 exposure; nor was cellular expression of factor VIII affected. 200 microM H2O2 induced cell contraction after 15 min which disappeared after 1 and 4 h, but was evident again after 24 h. Immediately after exposure, the filamentous structure of vimentin and tubulin disappeared, but normalized after 1 h. After 120 h, the cytoskeleton filaments were coarsened and disorganized, and an abundance of multinucleated giant cells were observed. Catalase (150 U/ml) abolished all effects of H2O2. One microM H2O2 did not induce any changes in HUVEC. Thus, the present concentrations of H2O2 did not induce cell necrosis or altered expression of factor VIII. Early, reversible cell contraction and depolymerization of cytoskeletal proteins were observed, followed by a delayed contraction and cell atypia after 200 microM H2O2.

Antibodies, Monoclonal↗
PubMed1999

Intermittent warm blood cardioplegia does not provide adequate myocardial resuscitation after global ischaemia.

OBJECTIVE: Intermittent warm blood cardioplegia is controversial, and many surgeons consider it inadequate for myocardial protection. The purpose of this study was to compare intermittent and continuous warm blood cardioplegia as resuscitation in hearts exposed to global ischaemia. METHODS: Pigs were put on cardiopulmonary bypass (CPB) and subjected to 30 min of warm, "unprotected", global ischaemia, followed by continuous (n = 7) or intermittent (n = 10, 12 ml/kg every 10 min) warm (34 degrees C) antegrade blood cardioplegia for 45 min (delivery pressure 75-80 mmHg) and weaned from CPB 45 to 60 min later. Indices of left ventricular function were acquired with the conductance catheter technique and pressure-volume loops at baseline and after 90 min of reperfusion. RESULTS: Cardioplegia was delivered during 17% of the cross-clamp time. Global left ventricular function, evaluated by preload recruitable stroke work (PRSW), was unchanged after continuous cardioplegia; 95 (76-130) (median (quartile interval)) to 91 (90-104) erg/ml x 10(3), but decreased after intermittent cardioplegia; 122 (100-128) to 64 (23-93) erg/ml x 10(3). Two pigs in the intermittent group weaned from CPB, but died before post-bypass measurement. A 95% confidence interval for the difference in post-bypass mean PRSW was estimated as 32 +/- 30 erg/ml x 10(3) (corresponding to P = 0.04 for comparison between treatments). The end-diastolic pressure-volume relation (EDPVR) increased from 0.17 (0.14-0.20) (continuous) and 0.15 (0.12-0.22) (intermittent) mmHg/ml to 0.27 (0.22-0.33) (P = 0.018) and 0.39 (0.25-0.66) (P = 0.005) mmHg/ml, respectively, indicating deterioration in diastolic function. No difference between groups was found in EDPVR, stiffness constant, troponin T release or myocardial water content. CONCLUSION: Following acute global ischaemia left ventricular global function was, in this model, less preserved using warm intermittent compared to warm continuous cardioplegia.

Animals↗
PubMed1999

Increased extracellular brain water after coronary artery bypass grafting is avoided by off-pump surgery.

OBJECTIVE: To determine if coronary artery bypass graft (CABG) surgery without cardiopulmonary bypass (CPB) avoids the brain swelling known to occur after CPB, to quantify these brain water compartment changes, and to identify the water shifts as due to intracellular or extracellular water. DESIGN: Prospective, controlled, and blinded. SETTING: Cardiac surgical unit in a university teaching hospital. SUBJECTS: Patients scheduled for CABG who were assigned to conventional (n = 10) or off-pump (n = 7) surgery according to their coronary anatomy. INTERVENTIONS: Magnetic resonance imaging (MRI) examinations were performed 1 day before surgery and 1 hour and 1 week after CABG surgery. MAIN OUTCOME MEASURES: Extracellular and intracellular water homeostasis was described quantitatively by calculating the averaged apparent diffusion coefficient of brain water using diffusion-weighted MRI. Blinded visual ordering of the images from the three examinations was performed according to brain size using conventional MRI. RESULTS: The average diffusion coefficient of brain water increased 4.7%+/-1.5% immediately after CABG with CPB and normalized after 1 week but did not change after CABG without CPB. No focal ischemic changes were seen in either group, and no gross neurologic deficits were observed. Visual analysis showed consistent brain swelling after CPB and variable changes in those operated without CPB. CONCLUSION: Changes consistent with increased extracellular brain water seen after CABG with CPB were not observed in patients undergoing CABG without CPB. The clinical significance of brain water changes and increased brain water content after surgery with CPB remains undefined.

Brain↗
PubMed1999

Post-ischaemic dysfunction does not correlate with release of cardiac troponin T in isolated rat hearts.

Cardiac troponin T (cTnT) is a highly sensitive and specific serum marker of irreversible cardiomyocyte injury. It is not clear whether cTnT also is a suitable marker of subtle, reversible injury. In the present investigation the relationship between cTnT release and function during the first 30 min of reperfusion after 30 min of global ischaemia, was investigated in isolated, retrogradely perfused rat hearts. Left ventricular systolic (LVSP), end-diastolic (LVEDP) and developed (LVDP) pressures, heart rate (HR), and coronary flow (CF) were measured. In one series of experiments (n=7) the kinetics of cTnT release during 30 min of reperfusion was investigated. An early, short-lasting peak of cTnT release appeared after 30 s of reperfusion. Then cTnT release gradually increased with a maximum after 20 min (from 0.08 +/- 0.03 before ischaemia to 2.16 +/- 0.40 ng min-1) (mean +/- SEM). In a second series of experiments (n=52) the relationship between cTnT release and cardiac function was investigated after 20 min of reperfusion. At this time point LVEDP increased (0 to 62 +/- 3 mmHg) and LVDP decreased (84 +/- 2 to 33 +/- 3 mmHg), but without any correlation with cTnT release. cTnT release was positively correlated to LVSP (P < 0.04, r=0.29), and negatively correlated to HR (P < 0.03, r=-0.31). cTnT concentration in the coronary effluent increased in parallel to increasing CF (P < 0.03, r=0.31). In conclusion, during the early reperfusion period there was no consistent correlation between cTnT release and dysfunction after global ischaemia in the isolated rat heart. Release of cTnT and post-ischaemic function appear to provide supplementary information in this particular model.

Animals↗
PubMed1999

Mechanical conversion of post-ischaemic ventricular fibrillation: effects on function and myocyte injury in isolated rat hearts.

Ventricular fibrillation (VF) and ventricular tachycardia (VT) are common phenomena during reperfusion. In experimental research many hearts have to be excluded from haemodynamic evaluation because of severe arrhythmias. Theoretically, electroconversion or mechanical conversion (MC) might be used to convert VF or VT. MC induces a physical shock analogous to a chest thump. The aim of this study was to investigate the efficacy of MC in isolated, perfused rat hearts, and to see whether MC itself induced myocardial cell injury and functional impairment. Langendorff-perfused rat hearts (n = 89) from several experimental series subjected to 30 min of global ischaemia and 60 min of reperfusion were retrospectively analysed. Left ventricular systolic (LVSP), end-diastolic (LVEDP), and developed (LVDP) pressures, coronary flow (CF), and heart rate (HR) were measured. If VF or VT continued for 1 min during reperfusion, MC was attempted by a flick of the forefinger to the right ventricle. If VF or VT still occurred, MC was repeated. Hearts that did not have regular beating after 20 min of reperfusion were excluded. Release of cardiac troponin T (cTnT) was measured before ischaemia and after 20 min of reperfusion. Forty-four out of 89 hearts had VF or VT during reperfusion. Thirty-five hearts were converted, 18 of which were converted by one or two MCs only. The higher the total number of MCs employed, the more cTnT was released. After 20 min of reperfusion, LVEDP, LVDP and CF were better in hearts with a higher number of MCs and with increased release of cTnT. After 60 min of reperfusion, LVEDP was still improved in hearts with more cTnT release, whereas LVSP was lower, and LVDP and CF were independent of the number of MCs. There was no consistent correlation between release of cTnT and heart dysfunction. In conclusion, MC effectively converted VF or VT. MCs increased post-ischaemic myocardial cell damage, as judged from increased cTnT release. Post-ischaemic dysfunction was partly attenuated in hearts with multiple MCs, and did not correlate with release of cTnT. We feel that MCs should not be used in isolated, perfused hearts.

Animals↗
PubMed1999

Endothelial injury and trapping of blood cells in human myocardium following coronary bypass surgery.

To investigate the focal myocytic and microvascular injury that develops during the first hour of reperfusion after hypothermic cardioplegic cardiac arrest, and to compare the influence of gentle versus more abrupt reperfusion, serial atrial biopsies were obtained from 14 patients undergoing uneventful coronary bypass surgery. The biopsies were taken before cardioplegia, at the start of reperfusion, and after 20 and 60 min of reperfusion. Transmission electron micrographs of biopsies examined by stereological techniques revealed endothelial injury. Following 20 min reperfusion there was accumulation of both red blood cells (p = 0.03) and polymorphonuclear leucocytes (p = 0.0004) were found. There was also intravascular accumulation of platelets (p = 0.008) and extravasation of red blood cells (p = 0.02), which increased throughout the observation period. If reperfusion was started with a gradual rise in temperature and pressure, the numbers of platelets in the microvessels were lower than following ordinary, abrupt reperfusion (p = 0.06). It is concluded that reperfusion injury is associated with microcirculatory disturbances with trapping of blood cells, changes which may be favourably modified by a gentle reperfusion technique.

Adult↗
PubMed1999

Does hypothermia or hyperkalemia influence the preconditioning response?

Ischemic preconditioning (IPC) is a potent mode of myocardial protection, but not in all models of cold cardioplegia. The present study investigates possible effects of hypothermia and hyperkalemia on the preconditioning response. Langendorff-perfused rat hearts were preconditioned (2 min global ischemia and 5 min reperfusion) or control-perfused prior to 35 min normothermic, global ischemia (series 1, n = 17 in each group); 50 min normothermic cardioplegia (St. Thomas's II) (series 2, n = 10 in each); 75 min 23 degrees C, global ischemia (series 3, n = 7 in each); or 5 h 6-8 degrees C, global ischemia (series 4, n = 9 in each). Left ventricular developed (LVDP) and end-diastolic (LVEDP) pressures, coronary flow (CF), heart rate, incidence of severe reperfusion arrhythmias, and release of troponin T (TnT) were measured. IPC attenuated reduction of LVDP and CF, and increase of LVEDP during reperfusion in series 1-3. TnT release was reduced by IPC in series 3 only. IPC did not attenuate dysfunction after hypothermic ischemia (series 4). Neither hyperkalemia nor moderate hypothermia alone inhibited the preconditioning response, but IPC was not protective in deep hypothermia.

Animals↗