Biomedical subjects

Rüdiger Vollandt

Publications and source records attributed to Rüdiger Vollandt.

11 recordsLinked to original sources

PubMed2006

Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells.

Cysteinyl leukotrienes (cysLT), i.e., LTC4, LTD4, and LTE4, are lipid mediators derived from the 5-lipoxygenase pathway, and the cysLT receptors cysLT1-R/cysLT2-R mediate inflammatory tissue reactions. Although endothelial cells (ECs) predominantly express cysLT2-Rs, their role in vascular biology remains to be fully understood. To delineate cysLT2-R actions, we stimulated human umbilical vein EC with LTD4 and determined early induced genes. We also compared LTD4 effects with those induced by thrombin that binds to protease-activated receptor (PAR)-1. Stringent filters yielded 37 cysLT2-R- and 34 PAR-1-up-regulated genes (>2.5-fold stimulation). Most LTD4-regulated genes were also induced by thrombin. Moreover, LTD4 plus thrombin augmented gene expression when compared with each agonist alone. Strongly induced genes were studied in detail: Early growth response (EGR) and nuclear receptor subfamily 4 group A transcription factors; E-selectin; CXC ligand 2; IL-8; a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif 1 (ADAMTS1); Down syndrome critical region gene 1 (DSCR1); tissue factor (TF); and cyclooxygenase 2. Transcripts peaked at approximately 60 min, were unaffected by a cysLT1-R antagonist, and were superinduced by cycloheximide. The EC phenotype was markedly altered: LTD4 induced de novo synthesis of EGR1 protein and EGR1 localized in the nucleus; LTD4 up-regulated IL-8 formation and secretion; and LTD4 raised TF protein and TF-dependent EC procoagulant activity. These data show that cysLT2-R activation results in a proinflammatory EC phenotype. Because LTD4 and thrombin are likely to be formed concomitantly in vivo, cysLT2-R and PAR-1 may cooperate to augment vascular injury.

Blood Coagulation↗

PubMed2005

The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice.

OBJECTIVE: Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention. METHODS AND RESULTS: The composition of immune cells in the innominate artery and abdominal aorta was examined in young, adult, and old apolipoprotein (apo) E(-/-) and wild-type mice on standard mouse chow. In the innominate artery of apoE(-/-) mice, adventitial T cells increased at 32, 52, and 78 weeks exceeding those of the intima by 6-, 24-, and 85-fold. Single T cells dominated in young mice, later T/B cell clusters emerged, and lymphoid-like structures reminiscent of inflammatory follicles formed preferentially in the abdominal aorta of old mice. Follicles contained organized sets of immune response-regulating cells: Interdigitating dendritic cells, T cell effectors, proliferating B cells, and plasma cells. Adventitial T cell inflammation was associated with a marked increase in transcripts of the chemokine MIP-1alpha in the aorta but not in spleen or liver. CONCLUSIONS: Adventitial lymphocyte infiltration and formation of inflammatory follicle-like structures in the abdominal aorta of old apoE(-/-) mice point to the adventitia as a site of local adaptive immune reactions during atherogenesis in hyperlipidemic mice.

Age Factors↗

PubMed2005

New concepts of multiple tests and their use for evaluating high-dimensional EEG data.

Recently, new concepts of type I error control in multiple comparisons have been proposed, in addition to FWE and FDR control. We introduce these criteria and investigate in simulations how the powers of corresponding test procedures for multiple endpoints depend on various quantities such as number and correlation of endpoints, percentage of false hypotheses, etc. We applied the different multiple tests to EEG coherence data. We compared the memory encoding of subsequently recalled and not recalled nouns. The results show that subsequently recalled nouns elicited significantly higher coherence than not recalled ones.

Acoustic Stimulation↗

PubMed2005

Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B12.

OBJECTIVE: Hyperhomocysteinemia is associated with atherosclerotic risk. Although vitamins can lower homocysteine (Hcy), information about effects on atherosclerosis is scarce. METHODS: We used carotid intima-media thickness (IMT) as an accepted marker of atherosclerotic changes. Fifty patients (60 +/- 8 years) with IMT> or =1 mm were included. In a double blind, randomized trial they received daily 2.5 mg folic acid, 25 mg Vitamin B6, and 0.5mg Vitamin B12 or placebo for 1 year. RESULTS: In the treatment group, Hcy decreased from 10.50 +/- 3.93 to 6.56 +/- 1.53 micromol/l (P < 0.0001), whereas it remained unchanged in the placebo group (10.76 +/- 2.36 versus 10.45+/-3.30 micromol/l). IMT decreased from 1.50 +/- 0.44 to 1.42 +/- 0.48 mm (P = 0.034) in the treatment group, whereas it increased from 1.47 +/- 0.57 to 1.54 +/- 0.71 mm in the placebo group. The mean individual changes of IMT between both groups differed significantly (-0.08 +/- 0.17 versus 0.07 +/- 0.25 mm, P = 0.019). Multiple regression analysis revealed that the observed effect on IMT depended only on medication. CONCLUSIONS: Vitamin supplementation significantly reduces IMT in patients at risk. This effect is independent of Hcy concentration.

Aged↗

PubMed2005

Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: selected parameters of coagulation and inflammatory system.

OBJECTIVE: Closed circuit extracorporeal circulation (CCECC) has been developed to reduce deleterious effects of standard cardiopulmonary bypass (CPB). This study compares the effects of CCECC (CORx system), CPB, and off-pump coronary artery bypass grafting (OPCAB) on red blood cell damage, coagulation activation, fibrinolysis and cytokine expression. METHODS: Thirty patients underwent coronary artery bypass grafting (CABG). Twenty of them were randomized into two groups: CCECC (n = 10), CPB (n = 10). While not randomized, OPCAB (n = 10) served as a separate reference group. CCECC and CPB patients received cardioplegic arrest. Interleukin 6 (IL-6), free hemoglobin (fHb), von Willebrand factor activity (vWf), thrombin-antithrombin-III-complex (TATc), prothrombin fragment 1.2 (F 1+2) and plasmin-antiplasmin complex (PAPc) were assessed preoperatively, perioperatively and 24 h postoperatively. RESULTS: CCECC showed significantly lower red blood cell damage than CPB (fHb: CCECC, 7.1+/- 5.7 micromol/l; CPB, 16.8+/-11.4 micromol/l; P = 0.025; OPCAB, 3.4+/-1.1 micromol/l). Perioperatively, CCECC exhibited significantly lower activation of coagulation and fibrinolysis than CPB, but did not differ from OPCAB (vWf: CCECC, 133+/-52%; CPB, 241+/-128%; P = 0.052; OPCAB, 153+/-58%; TATc: CCECC, 4.7+/-0.9 ng/ml; CPB, 31.1+/-15.8 ng/ml; P < 0.001; OPCAB, 2.4+/-0.6 ng/ml; PAPc: CCECC, 214+/-30 ng/ml; CPB, 897+/-367 ng/ml; P < 0.001; OPCAB, 253+/-98 ng/ml). In contrast, fibrinolysis markers and IL-6 were markedly increased in CCECC postoperatively (PAPc: CCECC, 458+/-98 ng/ml; CPB, 159+/-128 ng/ml; P < 0.001; OPCAB, 262+/-174 ng/ml; IL-6: CCECC, 123.4+/-49.8 pg/dl; CPB, 18.8+/-13.1 pg/dl; P < 0.001; OPCAB, 31.6+/-26.2 pg/dl). CONCLUSIONS: CCECC for CABG is associated with a significant reduction of red blood cell damage and activation of coagulation cascades similar to OPCAB when compared with conventional CPB while a delayed fibrinolytic and inflammatory activity was observed. These findings require further investigation to verify the promising concept of CCECC.

Acute-Phase Reaction↗

PubMed2004

Evaluation of bone-mineral density by digital X-ray radiogrammetry (DXR) in pediatric renal transplant recipients.

BACKGROUND: Loss of bone mass and increased fracture risk are known complications after renal transplantation in adults. Risk factors include donor source, dialysis status prior to transplantation, aetiology of renal disease, transplant rejection and drug therapy, particularly steroids. OBJECTIVE: In this preliminary study of quantification of bone loss in children after renal transplantion, we evaluated the applicability of digital X-ray radiogrammetry (DXR) of hand radiographs to estimate cortical bone mineral density (DXR-BMD). MATERIALS AND METHODS: A total of 23 renal transplant recipients (9 girls, 14 boys; age 6.5-20 years, median 16.3 years) underwent DXR measurements for calculation of DXR-BMD and metacarpal index (DXR-MCI) using radiographs of the non-dominant left hand. The duration between transplantation and the DXR evaluation, the duration of dialysis and medication were considered. The results were compared to a local age-matched and gender-matched reference data base. RESULTS: Our study revealed a significant decrease in bone mineral density compared to an age-matched and sex-matched normal population (P<0.05). In three patients the DXR-BMD was reduced more than -2.5 SD. In 12 patients the DXR-BMD was between -1 and -2.5 SD, and in 7 patients the DXR-BMD was in the normal range. In one patient, evaluation was not possible. Fractures were documented in three patients following transplantation. Reduced DXR-BMD was not significantly associated with immunosuppressive therapy or the duration of dialysis, and there was no significant correlation between DXR-BMD and the time between transplantation and DXR evaluation. CONCLUSIONS: Paediatric renal transplant patients show reduced DXR-BMD. In this preliminary study we demonstrated that DXR-BMD seems to be a reliable technique for quantification of demineralisation following renal transplantation in children.

Absorptiometry, Photon↗

PubMed2004

Intrauterine growth restriction ameliorates the effects of gradual hemorrhagic hypotension on regional cerebral blood flow and brain oxygen uptake in newborn piglets.

Data are scant regarding the development of cerebrovascular autoregulation in intrauterine growth-restricted (IUGR) newborns. We tested the hypothesis that IUGR improves the ability of neonates to withstand critical periods of gradual hemorrhagic hypotension by optimizing cerebrovascular autoregulation. Studies were conducted on 1-d-old anesthetized piglets divided into groups of normal weight (NW, n = 14, body weight = 1518 +/- 122 g) and IUGR (n = 14, body weight = 829 +/- 50 g) animals. Physiologic parameters, including regional cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)), were similar in NW and IUGR piglets under baseline conditions. Controlled arterial blood loss [hemorrhagic hypotension (HH)] induced a stepwise reduction of the mean arterial blood pressure of 49 +/- 3 mm Hg (mild HH), 39 +/- 3 mm Hg (moderate HH), and 30 +/- 3 mm Hg (severe HH) in seven NW and seven IUGR piglets (p < 0.05). In NW piglets, cortical CBF and CMRO(2) was reduced already at moderate HH (p < 0.05). A similar CMRO(2) reduction occurred during severe HH in NW and IUGR piglets (p < 0.05). In addition, during mild and moderate HH, primarily in IUGR piglets, an increase in regional CBF of brainstem, cerebellum, and thalamus was shown compared with baseline values (p < 0.05). Furthermore, under these conditions, cerebral cortex blood flow was maintained in newborn IUGR animals. In contrast, NW piglets exhibited a significant reduction in CBF (p < 0.05) during moderate HH. Thus, IUGR resulted in an improved ability to withstand critical periods of gradual oxygen deficit as shown by improved cerebrovascular autoregulation during hemorrhagic hypotension.

Adaptation, Physiological↗

PubMed2004

Chronic ultrastructural effects of temporary intraluminal shunts in a porcine off-pump model.

BACKGROUND: Temporary intraluminal shunts (TILS) are routinely used in off-pump revascularization to facilitate the anastomosis while maintaining myocardial blood supply. Whereas tourniquet-occlusion can cause vessel wall trauma, potentially adverse chronic effects of TILS on the coronary intima have not been evaluated yet. This chronic large animal study investigated ultrastructural effects of TILS on the vessel wall. METHODS: Four groups of acute and chronic pigs with either tourniquet-occlusion (TOUR) or TILS (40 kg; acute, n = 12; chronic, n = 20) were analyzed. Animals underwent median sternotomy, heparin (150 U/kg) administration, and left anterior descending coronary artery exposure. In groups with TOUR the left anterior descending coronary artery was temporarily occluded (10 minutes) with a tourniquet. In groups with TILS a silicone shunt (1.5 mm diameter, 12 mm length) was placed in the left anterior descending coronary artery more than 10 minutes and then removed, and the insertion was repaired. Thirty minutes after reperfusion all acute animals were sacrificed whereas chronic animals were extubated, maintained for 3 months, and then sacrificed. The left anterior descending coronary artery regions of occlusion or placement of the TILS silicone bulbs were examined histopathologically by scanning and transmission electron microscopy by a blinded pathologist. RESULTS: In both acute and chronic investigations animals in the TILS group exhibited significantly less morphologic damage than animals in the TOUR group. In the acute phase significantly more loss of cell junction (p = 0.037), loss of endothelium (p = 0.032), and intimal edema (p = 0.037) in the TOUR group than in the TILS group was observed. Three months later, characteristic features with a changed pattern were detected: vacuolization of the cell (p = 0.03), loss of cell junction (p = 0.042), and removal of basal membrane (p = 0.046) as well as extensive loss of endothelium (p = 0.003) in the TOUR group compared with the TILS group. CONCLUSIONS: Intimal lesions occur with both maneuvers early and late. However, animals in the TOUR group exhibited injuries significantly more often and more severely. Therefore, acute and chronic intimal integrity of the coronary vessel may be better preserved using TILS and may thus have a positive impact on the extent of de novo stenosis and long-term prognosis of the revascularized region.

Animals↗

PubMed2003

Are mechanical valves with enhanced inner diameter advantageous in the small sized aortic annulus?

BACKGROUND: Mechanical bileaflet valves with enhanced inner diameter may offer superior hemodynamic properties in patients with a small aortic annulus. The aim of this clinical study was to compare these valves with standard bileaflet prostheses in vivo. METHODS: Mechanical aortic valve replacement for combined stenosis and regurgitation was performed in 47 patients with standard CarboMedics prostheses (CM: 21 mm, 23 mm, 25 mm) and two types of diameter enhanced St. Jude Medical prostheses (SJM-AHPJ: 21 mm, 23 mm, 25 mm; SJM-Regent: 21 mm, 23 mm). Transvalvular mean gradients (TVG) were assessed intraoperatively by means of transesophageal echocardiography (TVG(TEE)) and simultaneous direct pressure monitoring of the left ventricle and the ascending aorta (TVG(CATH)), as well as early (3 months) and late (9 months) postoperatively by means of transthoracic echocardiography (TVG(TTE)). Left ventricular muscle mass was assessed preoperatively, early, and late postoperatively to evaluate remodeling capacity. RESULTS: In all valve types and sizes, both TVG assessments exhibited consistent findings. Small-sized conventional valves of 21 mm showed a marked initial TVG. In contrast, both valve types with enhanced inner diameter exhibited significantly lower TVG comparable with those achieved with larger valves (TVG(CATH) CM 21 mm, 15.6 +/- 3.9 mm Hg; SJM-AHPJ 21 mm, 11.9 +/- 1.6 mm Hg; SJM-Regent 21 mm, 9.9 +/- 1.1 mm Hg; CM 23 mm, 7.8 +/- 0.8 mm Hg; SJM-AHPJ 23 mm, 7.7 +/- 1.4 mm Hg; SJM-Regent 23 mm, 9.5 +/- 1.8 mm Hg). During the postoperative course TVG remained constant in all valve types and sizes. Left ventricular muscle mass, however, diminished markedly in all valves without exhibiting significant differences between size matched valve types. CONCLUSIONS: In patients with a small aortic annulus, who require a 21-mm valve, diameter-enhanced prostheses provide lower transvalvular gradients than conventional valves. However, in the intermediate clinical course, appropriate left ventricular remodeling occurred in all patients independent of the size and the type of the valve.

Aged↗

PubMed2003

Physiological coagulation can be maintained in extracorporeal circulation by means of shed blood separation and coating.

OBJECTIVE: Conventional extracorporeal circulation results in an activation of coagulation cascades. Coating of extracorporeal circulation tubes as well as avoidance of shed blood recirculation have been shown to reduce these phenomena. We evaluated a new shed blood separation system (AVANT D 970) utilizing a coated cardiopulmonary bypass tube system (PHISIO). METHODS: Forty patients (62 +/- 10 years) underwent isolated coronary revascularization. Four groups (n = 10/group) were defined: no extracorporeal circulation, conventional uncoated extracorporeal circulation, uncoated extracorporeal circulation with shed blood separation, and coated extracorporeal circulation with shed blood separation. Thrombin-antithrombin complex and free Hb were analyzed and statistically compared. RESULTS: Conventional extracorporeal circulation exhibited the highest intraoperative activation of coagulation (thrombin-antithrombin complex: extracorporeal circulation, 31.1 +/- 15.8 microg/L; uncoated extracorporeal circulation with shed blood separation, 15.3 +/- 7.8 microg/L; coated extracorporeal circulation with shed blood separation, 8.1 +/- 4.8 microg/L; no extracorporeal circulation, 2.4 +/- 0.6 microg/L; P <.05 extracorporeal circulation vs all others) and red blood cell damage (free Hb: extracorporeal circulation, 16.8 +/- 11.4 micromol/L; uncoated extracorporeal circulation with shed blood separation, 10.3 +/- 3.5 micromol/L; coated extracorporeal circulation with shed blood separation, 6.8 +/- 2.9 micromol/L; no extracorporeal circulation, 3.4 +/- 1.1 micromol/L; P <.05 extracorporeal circulation vs no extracorporeal circulation, coated extracorporeal circulation with shed blood separation). Coated extracorporeal circulation with shed blood separation showed only slight activation and cell trauma, which did not differ significantly from no extracorporeal circulation. CONCLUSIONS: Combination of coating and avoidance of shed blood recirculation maintained physiological coagulation levels and markedly reduced red blood cell trauma in extracorporeal circulation procedures. These combined modalities may therefore offer an alternative for off-pump procedures in patients with contraindications for conventional extracorporeal circulation.

Aged↗

PubMed2002

Revascularization during acute myocardial infarction: risks and benefits revisited.

BACKGROUND: Indication for immediate revascularization during acute myocardial infarction (MI) is debated. Drug-resistant crescendo angina, as well as hemodynamic compromise, however, often requires acute operation. In this study the differential risks of acute coronary artery bypass grafting with and without MI were stratified. METHODS: Five hundred eighteen patients undergoing isolated coronary artery bypass grafting were investigated. Thirty-nine patients underwent acute revascularization because of enzyme-proven or electrocardiogram-proven MI accompanied by crescendo angina, hemodynamic compromise, or both. They were compared with 33 emergent, 63 urgent, and 383 elective patients without MI. Preoperative risk factors for early mortality and necessity of continuous venovenous hemofiltration were analyzed by means of logistical regression analysis. Perioperative data were compared. RESULTS: Early mortality of the MI cohort was 15.4%, in contrast to 15.2% in emergent, none in urgent, and 2.1% in elective patients. Left internal thoracic artery was used in 87% of MI, 97% of emergent, 94% of urgent, and 97% of elective patients. Intraaortic balloon pump was necessary in 50% of MI patients, 27% of emergent, 6.3% of urgent, and 3.1% of elective cases. Continuous venovenous hemofiltration was performed in 29% of MI patients, 15% of emergent, 4.9% of urgent, and 3.4% of elective patients. Hemodynamic instability significantly increased the odds ratio for early mortality and continuous venovenous hemofiltration. CONCLUSIONS: Patients undergoing acute revascularization carried an elevated risk to die early notwithstanding the presence or absence of acute MI. Liberal use of left internal thoracic artery grafts was not detrimental in acute patients whereas liberal use of intraaortic balloon pump was beneficial. In almost 30% of MI patients, continuous venovenous hemofiltration was not necessary, implying a severely impaired perioperative hemodynamic condition. Immediate revascularization in the presence of acute MI is therefore indicated although it may be addressed as a separate high-risk group.

Aged↗