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Biomedical subjects

Marcus Baumann

Publications and source records attributed to Marcus Baumann.

11 recordsLinked to original sources
PubMed2007

Transient AT1 receptor-inhibition in prehypertensive spontaneously hypertensive rats results in maintained cardiac protection until advanced age.

OBJECTIVE: In young spontaneously hypertensive rats (SHR), transient angiotensin II type 1 receptor (AT1R) blockade decreases blood pressure for a prolonged period. We tested the hypothesis that transient AT1R blockade in SHR leads to cardiac protection until advanced age. METHOD: Wistar-Kyoto rats, SHR and transiently losartan-treated SHR (SHR-Los) (20 mg/kg per day; weeks 4-8 of age) were followed up until week 72 (n=9 each group), including repeated echocardiography, radiotelemetric investigations and 24-h urine collection. End-point measurements comprised left ventricular function parameters, left ventricular histomorphology and molecular biology (types I and III collagen, brain natriuretic peptide, AT1R mRNA) as well as renal morphology. RESULTS: Prehypertensive treatment with losartan, but not with the general vasodilator hydralazine, reduced blood pressure until age 48 weeks. In untreated SHR, the end-diastolic volume increased from week 36 and the left ventricular ejection fraction fell from week 48. In contrast, age-related changes in end-diastolic volume and ejection fraction were comparable in SHR-Los and Wistar-Kyoto rats up to age 60 weeks. At age 72 weeks, the ejection fraction was reduced in SHR-Los but higher than that in untreated SHR (ejection fraction: Wistar-Kyoto rats, 58 +/- 3%; SHR, 39 +/- 3%; SHR-Los, 46 +/- 3%; P < 0.01 and P < 0.05, respectively). The heart weight/body weight ratio (SHR-Los, 4.7 +/- 0.1 g/kg; SHR, 5.2 +/- 0.2 g/kg) and cardiac brain natriuretic peptide mRNA levels were improved by treatment. Left ventricular histomorphology and 24-h albuminuria were significantly improved in SHR-Los (41 +/- 5 mg/day; SHR, 80 +/- 22 mg/day; P < 0.05). CONCLUSION: In young SHR, transient AT1R blockade, not blood pressure lowering, attenuates the development of hypertension and exerts cardioprotective effects up to age 72 weeks.

Age Factors↗
PubMed2006

Fully automated continuous flow synthesis of 4,5-disubstituted oxazoles.

[Structure: see text] A multipurpose mesofluidic flow reactor capable of producing gram quantities of material has been developed as an automated synthesis platform for the rapid on-demand synthesis of key building blocks and small exploratory libraries. The reactor is configured to provide the maximum flexibility for screening of reaction parameters that incorporate on-chip mixing and columns of solid supported reagents to expedite the chemical syntheses.

Journal Article↗
PubMed2006

Imatinib attenuates end-organ damage in hypertensive homozygous TGR(mRen2)27 rats.

Imatinib specifically inhibits receptor tyrosine kinase signaling and is clinically used to treat leukemia. Receptor tyrosine kinases not only mediate tumor growth but also initiate adverse signaling in heart failure. We investigated whether imatinib, by inhibiting the platelet-derived growth factor receptor-beta (PDGFRbeta), prevents cardiac and renal damage in TGR(mRen2)27 (Ren2) rats. Eight-week-old male homozygous Ren2 and Sprague Dawley rats were treated either with imatinib (30 mg/kg; STI-571) or placebo for 8 weeks (Ren2 n=12 for each group; Sprague Dawley n=6 for each group). Imatinib did not affect blood pressure or left ventricular (LV) hypertrophy in both groups. Imatinib attenuated the decline in fractional shortening (imatinib versus Ren2 placebo 45+/-4.5% versus 32+/-3%; n=7-11; P<0.05) and in diastolic function in Ren2 rats (baseline diastolic dP/dt corrected for systolic blood pressure Ren2 imatinib versus Ren2 placebo 38.6+/-0.67 versus 35.3+/-0.41 [1 . s(-1)]; n=7-11; P<0.05). This was associated with decreased cardiac fibrosis and decreased activation of PDGFRbeta and extracellular signal-regulated kinase 1/2. Renal microvascular hypertrophy and perivascular fibrosis in Ren2 rats were significantly decreased by imatinib. In vitro, imatinib blocked angiotensin II-induced activation of the PDGFRbeta and significantly decreased fibroblast proliferation and collagen production. In conclusion, imatinib did not affect LV hypertrophy but attenuated the decline in cardiac function and reduced renal microvascular damage associated with reduced activation of the PDGFRbeta. The simultaneous improvement in both heart and kidneys suggests that inhibition of the PDGFRbeta has broad protective effects that may provide novel avenues for a blood pressure-independent protection against end-organ damage.

Animals↗
PubMed2003

New model for simultaneous heart and kidney transplantation in mice.

In clinical settings, combined heart and kidney transplantation results in a lower incidence of cardiac graft and renal graft rejection as compared to isolated heart and kidney transplantation. To study the phenomenon in an experimental setting, we developed a model of combined heart and kidney transplantation in mice. According to our technique, we kept the patch of the infrarenal aorta and inferior vena cava (IVC) as long as possible during the donor's kidney explantation, and then, after finishing the kidney implantation with conventional techniques, we anastomosed the innominate artery and pulmonary artery of the heart graft to the patch of the infrarenal aorta and IVC of the renal graft, respectively, instead of the recipient's aorta and IVC. With the use of our method, combined heart and kidney transplantation in mice can be performed to get enough suture room for the second graft, to avoid prolonging the occlusion time of the recipient's circulation, and to profoundly decrease postoperative complications such as paraplegia and mortality. Of the 14 recipients with combined heart-kidney isografting, 10 have been successful (71.4%), surviving over 100 days with normal function of both grafts, and with lack of change in histological appearance. This suggests that the technique is feasible and reliable.

Animals↗
PubMed2003

The heart, macrocirculation and microcirculation in hypertension: a unifying hypothesis.

Epidemiological studies in the past decade have stressed the importance of both pulse pressure and mean arterial pressure (MAP) as important risk factors in hypertension-related cardiovascular disease. Pulse pressure and MAP are determined by different segments of the cardiovascular system. Pulse pressure is the pulsatile component of the blood pressure curve. It is determined by left ventricular ejection, the cushioning capacity (compliance) of the large arteries, and the timing and intensity of wave reflections from the microcirculation. MAP is the steady component; it is determined by cardiac output and peripheral (micro)vascular resistance. To a large degree, the structural design of the heart and vascular tree determine the pulse pressure and MAP, in addition to the propagation of the pressure wave through the vasculature. Pressure and flow, in contrast, influence the composition and geometry of the heart and vasculature. Hypertensive disease is associated with important structural alterations of the heart, such as hypertrophy and fibrosis, and of the vasculature, such as large artery stiffening, small artery remodelling and microvascular rarefaction. Recent basic research has revealed some of the molecular pathways involved in the remodelling of the cardiovascular system under the influence of physical forces. For correct understanding of the pathophysiology of hypertensive disease, its risks for target-organ damage and its effective treatment, both the pulsatile and steady components of the blood pressure curve must be considered.

Antihypertensive Agents↗
PubMed2003

Primary failure of arteriovenous fistulae in auto-immune disease.

BACKGROUND/AIM: Chronic haemodialysis depends on an arteriovenous fistula. Primary failure of vascular access is a common problem which is mainly related to thrombosis. As ambulatory surgery is common, it is mandatory to identify patients with a high thrombophilic risk to allow better prevention (anticoagulation) and direct re-intervention after thrombosis. The purpose of this study was to determine thrombophilic risk factors for primary access failure in order to identify patients at risk before the operation. METHODS: We performed a retrospective study on 62 chronic haemodialysis patients who received permanent vascular access. We evaluated established risk factors for chronic access failure as well as the number of earlier shunt operations in these patients. RESULTS: The patients predominantly suffered from auto-immune diseases. The frequency of a successful first vascular access was above average (92.5%). We identified four major risk factors for primary access failure: number of previous vascular access thromboses (p < 0.01; R = 0.96), pre-existing thrombophilic risk factors (p < 0.01), pre-operative fibrinogen (p < 0.02), and vasculitis (p < 0.01). CONCLUSIONS: We identified four risk factors which allowed an individual risk evaluation. Among the factors investigated, the activity of the auto-immune disease was the most striking. Our data suggest not to perform a vascular access during an active period of vasculitis.

Adolescent↗
PubMedDate not supplied

Functional and structural postglomerular alterations in the kidney of prehypertensive spontaneously hypertensive rats.

The kidney plays a major role in the development of hypertension. Following the Borst-Guyton theory of an altered set-point for fluid and electrolyte homeostasis we aim to investigate functional and structural renal parameter during the development of hypertension. Therefore we focus on counter current exchange related factors. We compared 4 and 8 weeks old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) concerning basic renal parameters as creatinine and phosphorus clearance and urinary osmolality. Mean arterial pressure (MAP) was measured intra-arterially. Vasa recta were investigated using immunohistochemistry for alpha-smooth-muscle actin (ASMA) and plastification for geometric analyses. Blood pressure was not yet significantly elevated in SHR at 4 weeks but at 8 weeks it was higher in SHR (116+/-7 vs. 102+/-4 mm Hg; p<0.01). Kidney weight/body weight ratio was lower in SHR at both ages. In 4 weeks old SHR, phosphorus clearance and urinary osmolality were decreased compared to WKY [0.02+/-0.01 vs. 0.05+/-0.02 (ml/min* 100 g BW) p < 0.03; 14.2+/-2.2 vs. 18.9+/-2.9 (osmol/kg*24 h urine) p < 0.051 indicating reduced tubular reabsorption. At 8 weeks phosphorus clearance and urinary osmolality were comparable to WKY. alpha-Actin was found in vasa recta in a 4-times higher degree in SHR with a predominant location in the outer medulla. Radii of vasa recta in the outer medulla decreased during development. In plastificated sections vasa recta of SHR revealed sphincter-like pattern. Functional and structural alterations related to the counter current exchanger are already evident in prehypertensive SHR. During development of hypertension both factors get adapted to higher blood pressure level. Sphincter-like structures in vasa recta suggest contractility of pericytes/vascular smooth muscle cells (vSMC). As these were just seen in SHR that might allude to a higher potential to contract. We conclude that differences in postglomerular structure and function may contribute to the development of hypertension in SHR.

Animals↗
PubMedDate not supplied

Prolonged catheter survival in intermittent hemodialysis using a less thrombogenic micropatterned polymer modification.

Adequate vascular access is a major prerequisite for hemodialysis treatment. Catheter related complications, in particular thrombus formation, are frequent, difficult to handle, and cost intensive. We investigated whether a new surface modified catheter containing a microdomain structure is beneficial for catheter survival. Surface thrombogenicity of standard double lumen catheters (STD-DC) and surface modified film-coated domain structured double lumen catheters (FCDS-DC) consisting of a novel reactive polyurethane copolymer coating was assessed by measurement of thrombinantithrombin (TAT) III complex in vitro. Furthermore, in a randomized observational study with 20 patients on hemodialysis, we analyzed catheter survival of either STD-DC (GamCath GDK 11 French, length 12.5 or 15 cm) or FCDS-DC (GamCath Dolphin GDK 11 French, length 12.5 or 15 cm). Catheter care protocol was identical, and dialysis treatment parameters were kept constant in both groups. In vitro measured surface thrombogenicity was reduced in the modified catheter compared with standard catheter. The clinical investigation revealed that both number of days before catheter removal according to clinical requirements and number of treatments per catheter were significantly higher with the modified catheter as compared with the standard catheter (14.5 vs. 10.3 days; 7 vs. 4 treatments; p < 0.03, Fisher-Yates test). Micropatterned surface coating with a polyurethane polymer significantly increased catheter survival and the number of treatments per catheter.

Acute Kidney Injury↗
PubMedDate not supplied

Serum C3 complement concentrations correlate with liver function in patients with liver cirrhosis.

BACKGROUND/AIMS: The aim of this study was to investigate whether C3 and C4 serum complement concentrations have prognostic relevance for patients with liver cirrhosis. METHODOLOGY: Serum complement concentrations of C3 and C4 were measured in 69 patients with liver cirrhosis and correlated with the Child-Pugh score. RESULTS: C3 concentrations were 1.06+/-0.21 g/L in patients with Child-Pugh A liver cirrhosis and significantly lower in Child-Pugh B (0.78+/-0.24 g/L) and even lower Child-Pugh C (0.49+/-0.14 g/L) (p=0.006 B vs. A, p<0.001 C vs. B). Patients with consecutive hepatorenal syndrome (HRS) had the lowest C3 concentrations (0.44+/-0.05 g/L (Child-Pugh C +HRS) vs. 0.54+/-0.06g/dL (Child-Pugh C -HRS); p<0.05). C4 concentrations were 0.21+/-0.08 in Child-Pugh A and significantly lower in Child-Pugh B (0.11+/-0.04) and Child-Pugh C (0.09+/-0.04) patients (p<0.001). There was a negative correlation between C3 (r = -0.81, p<0.001) and C4 (r = -0.51, p<0.05) concentrations and the Child-Pugh score. CONCLUSIONS: Serum complement concentrations of C3 and C4 correlate negatively with the Child-Pugh score in patients with liver cirrhosis. C3 concentrations are lower in those Child-Pugh C cirrhosis patients with consecutive development of HRS.

Bacterial Infections↗