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Biomedical subjects

T Walther

Publications and source records attributed to T Walther.

At least 37 records · Page 2Linked to original sources

Minimally invasive mitral valve surgery.

Minimally invasive mitral valve surgery (MIC-MVS) was introduced into clinical practice in the mid 1990s. Since then it has evolved as the standard technique at some specialized centers. The routine technique includes femoral access for extracorporeal circulation, a right lateral minithoracotomy and direct aortic clamping using special instruments. Different techniques leading to some variations have been described. There is no prospectively randomized trial comparing minimally invasive with conventional mitral valve surgery. However, several series including large patient numbers and up to 8 years of follow-up have been published. Literature results as well as different aspects of minimally invasive MVS are discussed in this review, including the development, the current technique and future perspectives. Regarding MIC-MVS the word is that it is a safe and effective operation. Lateral minithoracotomy access offers excellent exposure, visualization can be further enhanced when using endoscopic cameras. All different mitral valve repair procedures can be performed even in the presence of complex pathologies. The repair rate is excellent and reaches 75%. Patient recovery is fast leading to a significant improvement in individual quality of life. MIC-MVS can now be considered the standard approach and will reach more widespread clinical application.

Cardiac Surgical Procedures↗

[Peripartum cardiomyopathy-the (un)known obstetricalcardiologic emergency situation].

Peripartum cardiomyopathy (PPCM) is rare cardiac complication afflicting women during pregnancy or until 5 months post partum with the typical signs of acute cardiac failure. PPCM is similar to dilated cardiomyopathy (DCM) in terms of symptoms, histopathology and treatment but is characterized by a better outcome with a high rate of spontaneous normalization of left-ventricular size and function. The understanding of the etiology is limited. However, viral myocarditis and autoimmune factors might be involved in the development of PPCM. Clinically, PPCM shows pulmonary symptoms such as dyspnea, tachypnea and coughing. The diagnosis is finally established by echocardiography. It has to be assumed that PPCM is often undetected or misdiagnosed because of the low incidence, the unspecific symptoms and the fact that other pregnancy-related factors have similar clinical appearance. The treatment is also unspecific and similar to DCM and acute cardiac failure. The severity of the disease requires an interdisciplinary approach in a perinatal center with consequent follow-up of the patients for risk stratification including echocardiography.

Adult↗

Electron energy-loss spectroscopic profiling of thin film structures: 0.39 nm line resolution and 0.04 eV precision measurement of near-edge structure shifts at interfaces.

The method of energy-loss spectroscopic profiling of interfaces, planar defects and thin film structures in a transmission electron microscope with an imaging filter is introduced. Ways to calculate true chemical profiles with near-atomic line resolution are described. An application to the perovskite system (La,Ca)MnO(3)/SrTiO(3) demonstrates that the technical merit of this method is the simultaneous achievement of high resolution (down to 0.39nm line resolution), high chemical sensitivity (around 1at% standard deviation) and very high precision in the measurement of shifts of edge onsets and energy-loss near-edge structure details (down to 0.04eV). The combination of these characteristics makes the method a powerful tool for the quantification of diffusion and segregation of elements on the atomic scale in a variety of materials systems.

Journal Article↗

Effects of kinins on mammalian spermatozoa and the impact of peptidolytic enzymes.

Effects of kinins, mainly bradykinin (Bk), and other components of the kallikrein-kinin system on sperm motility and further fertility-related functions have been described repeatedly. However, reported data are in part controversial and the mechanism of kinin effects on sperm motility is not yet understood. In the present report we describe a significant promoting effect of Bk on sperm motility at subnanomolar concentrations. This effect was stabilized and even increased by suppression of Bk hydrolysis in semen samples. As sperm membrane-bound angiotensin-converting enzyme and neutral metalloendopeptidase are mainly involved in Bk hydrolysis, an effective cocktail of enzyme inhibitors promoting the sperm motility consists of phosphoramidon and lisinopril (both at 10-7 m). The effects of Bk on sperm cells are not mediated by the B2 Bk receptor. Using several biochemical, molecular and genetic methods we could not detect any Bk receptor on spermatozoa.

Angiotensin-Converting Enzyme Inhibitors↗

Impact of diabetes mellitus on cardiac surgery outcome.

BACKGROUND: Diabetes mellitus is an established independent risk factor related to significant morbidity and mortality after cardiac surgical procedures. METHODS: Data on 16,184 patients undergoing cardiac surgery with and without cardiopulmonary bypass between April 1996 and August 2001 were prospectively evaluated. Diabetes mellitus as a patient related risk factor was subjected to univariate analysis to identify potential associations to 28 intra- and postoperative outcome variables. Outcome variables having a significant association with diabetes mellitus (p < 0.05) were then subjected to a stepwise logistic regression model to identify the influence of diabetes mellitus as compared to additional 30 different patient related risk factors and treatment variables. Diabetes mellitus was defined as glucose intolerance treated either dietary, with oral hypoglycemics or with insulin. RESULTS: Overall prevalence of diabetes mellitus was 33.3 %. Compared to non-diabetic patients the group with diabetes mellitus was older (p < 0.0001) and had a significantly lower ejection fraction (p < 0.0001). 15 outcome variables having a significant association with diabetes mellitus were identified. Furthermore, diabetes mellitus could be identified as an independent predictor for 7 postoperative outcome variables (prolonged ICU-stay, sternal instability and/or infection, sternal revision and refixation respiratory insufficiency, postoperative delirium, perioperative stroke, renal dysfunction, postoperative reintubation). CONCLUSION: Diabetes mellitus is a significant independent predictor for several postoperative outcome variables after cardiac surgery associated with higher postoperative morbidity and prolonged hospital stay.

Aged↗

Epicardial treatment of atrial fibrillation using cryoablation in an acute off-pump sheep model.

BACKGROUND: The purpose of this study was to test the feasibility and effectiveness of cryoablation therapy (SurgiFrost trade mark CryoCath, Endocare Inc., Irvine, California, USA) for linear epicardial treatment of atrial fibrillation in an acute off-pump sheep model. METHODS: After thoracotomy, we performed epicardial cryoablation (2 min intervals at -160 degrees C) with pacing electrodes positioned at the left atrial appendage (LAA), the pulmonary veins (PVs), the right atrial appendage (RAA), and the vena cava cranialis (VCC) in 8 sheep. Circular epicardial ablations were performed with online temperature measurement in the ascending aorta and in the esophagus. The sheep were sacrificed two hours after ablation procedure, and heart, lungs, and esophagus were retrieved for histological examination. Out of all 8 sheep, histo-pathological analysis was performed on the RAA and VCC in 6 sheep and on the CAA and PV in all 8 sheep. RESULTS: Thin-walled structures such as PVs and VCC showed electrical isolation. No significant changes in temperature in the descending aorta and the esophagus were observed. There was evidence of extensive transmural alteration including vascular lesions, myocardial degeneration and necrosis as well as epi- and endocardial necrosis in the left atria in three of 8 cases, in the right atria in 5 of 6 cases, in the VCC in 6 of 6 cases, and in the PV in 5 of 8 cases. Mild lesions of the muscular layer of the esophagus were found in 7 of 8 cases. CONCLUSIONS: Epicardial cryoablation is not effective on thicker tissues like LAA and RAA due to the rewarming of the current blood flow. However, thin tissues like VCC and PV can be isolated. Further chronic studies are necessary to evaluate the potential for regeneration of adjacent structures.

Animals↗

Joint symbolic dynamic analysis of beat-to-beat interactions of heart rate and systolic blood pressure in normal pregnancy.

Pregnancy induces important changes in the autonomic control. Measures of heart rate (HR) variability and systolic blood pressure (SP) variability are sensitive to those changes. The interactions between HR and SP are complex and strongly non-linear. Therefore they cannot be completely described by linear analysis techniques. A study of joint symbolic dynamics is presented as a new short-term non-linear analysis method to investigate the interactions between HR and SP. Continuous, non-invasive 30 min blood pressure recordings (Portapres) of 25 pregnant and 14 non-pregnant women were analysed. Time series of beat-to-beat HR and SP were extracted. Using the concept of joint symbolic dynamics, HR and SP changes were transformed into a bivariate symbol vector. Subsequently, this symbol vector was transformed into a word series (words consisting of three successive symbols), and the probability of occurrence of each word type was calculated and compared between both groups. Significant differences were found in five word types between pregnant and non-pregnant women: w0,4(0.021+/-0.011 against 0.008+/-0.006; p = 0.022), w4,6(0.020+/-0.010 against 0.007+/-0.003; p = 0.001), w3,2(0.004+/-0.003 against 0.007+/-0.003; p = 0.038), W6,5(0.009+/-0.007 against 0.023+/-0.008; p< 0.001) and w3,6(0.011+/-0.007 against 0.023+/-0.008; p = 0.001). Joint symbolic dynamics provides an efficient non-linear representation of HR and SP interactions that offers simple physiological interpretations.

Adult↗

Regulation of matrix metalloproteinases and effect of MMP-inhibition in heart transplant related reperfusion injury.

PURPOSE: Metalloproteinases (MMPs) regulate extracellular matrix turnover and degrade basal lamina. Aim of the study was to examine the regulation of MMPs and the effect of an MMP inhibitor in transplant related ischemia/reperfusion injury. METHODS: Heterotopic cardiac transplantation was performed after 4 h of ischemia in three groups of six rats: allografts (black hooded inbred strain, PVG donor/August Copenhagen Irish inbred strain recipient); allografts treated with a competitive MMP-inhibitor (Batimastat) 15 mg/kg every 24 h; isografts (PVG donor and recipient). Normal PVG hearts served as a control. Hearts were explanted after 72 h of reperfusion. Expression of MMP-2 and -9 was measured using gelatin zymography. Proteolytic activity was measured using a gelatinase activity assay. Myeloperoxidase activity and tumor necrosis factor-alpha (TNF-alpha) were measured as markers of inflammatory response. Immunostaining for collagen IV and laminin was used to study degradation of basal lamina. RESULTS: There was a significant increase of MMP-2 expression in allografts (2271+/-571 microg/ml) as compared to normal (683+/-139 microg/ml) and the Batimastat-treated (259+/-140 microg/ml, P<0.05) groups. Although pro-MMP-2 expression was equally high in the untreated iso- and allograft group (75+/-23 versus 62+/-30 microg/ml) MMP-2 expression in the isograft hearts was significantly lower (359+/-267 microg/ml) suggesting activation of the pro-form by an immunologic mechanism. Pro-MMP-9 levels were significantly higher in the untreated iso- and allograft groups as opposed to normal hearts and MMP-inhibited hearts. MMP-9 was completely inhibited by Batimastat treatment. Collagenolytic activity was lower in the treated group as compared to untreated allografts (538+/-140 versus 384+/-97 microg/ml, P<0.05), demonstrating effective inhibition of MMPs by Batimastat. In the treated group a lesser extent of basement membrane component alterations could be demonstrated by laminin and collagen IV staining. There was a significant reduction in myeloperoxidase activity (P=0.027) as well as lower TNF-alpha levels (ns) in the in the Batimastat treated group. CONCLUSION: Ischemia leads to an increase in MMP expression and degradation of basal lamina. This process is enhanced in allografts as compared to isografts suggesting additional activation of MMPs by immunologic mechanisms. MMP-inhibition is effective in preventing the proteolytic activity of MMPs and may alter the host rejection response by preserving extracellular matrix components and basement membranes.

Animals↗

Vacuum-assisted venous drainage in complex congenital cardiac surgery.

Here, we report on a case of temporary neurological damage following conduit replacement from the right ventricle to pulmonary artery during which vacuum-assisted venous drainage was used. We will discuss the benefits and risks of this technique with potential arterial air embolism despite the use of arterial line filters. We will also make recommendations for avoiding such complications.

Adult↗

Mediastinitis and cardiac surgery--an updated risk factor analysis in 10,373 consecutive adult patients.

BACKGROUND: Deep sternal wound infection (DSWI) remains a serious complication after cardiac surgery. New evolving techniques including the utilization of internal mammary arteries (IMA), beating heart procedures, and minimal invasive surgery (MIC) require an updated risk factor analysis to identify high risk patients in order to improve perioperative treatment. METHODS: 10,373 consecutive patients receiving cardiac surgery between May 1996 and August 1999 were evaluated: 9,303 underwent full sternotomy whereas a minimally invasive (MIC) approach using partial sternotomy or lateral thoracotomy was used in 1,070 patients. DSWI was defined as the evidence of mediastinitis seen at reoperation along with one or more of the following: positive culture of mediastinal fluid, positive blood culture or temperature higher than 38 degrees C and/or leukocytosis. RESULTS: The overall incidence of DSWI in the "full sternotomy" group was 1.44 % (134 of 9,303). Univariate risk factor analysis showed a significant influence of IMA use, ICU / IC treatment > 5 days, postoperative ventilator time > or = 72 h, need for reexploration, diabetes, surgery time > or = 180 min, assist device implantation (including use of IABP), peripheral vascular disease and increased body mass index. Multivariate analysis identified double IMA, ICU treatment > 5 days, single IMA, diabetes, reexploration and increased body mass as significant risk factors. No mediastinitis was observed in the MIC group. CONCLUSION: As DSWI is related to sternotomy, a MIC approach should be considered for patients at high risk for DSWI. IMA takedown as a pedicled graft should be especially avoided in patients with diabetes since the risk for postoperative mediastinitis is unacceptably high in this patient group.

Aged↗

Cardiac malformations associated with the Holt-Oram syndrome--report on a family and review of the literature.

The Holt-Oram syndrome (HOS) is characterized by mild-to-severe congenital cardiac defects and skeletal abnormalities of the upper limb. The most common cardiac disorder is an ostium secundum atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. Electrocardiographic abnormalities, such as various degrees of atrioventricular block, have also been reported. In addition, hypoplastic peripheral vessels of the upper limbs have been observed. Here, we will report about a family with three sons having HOS, and we will detail the cardiac spectrum of HOS as reported in the literature.

Adult↗

[Heart rate and blood pressure interaction in normotensive and chronic hypertensive pregnancy].

Pregnancy has impact on autonomic control. Since hypertensive pregnancy disorders are a major cause of maternal mortality we investigated the baroreflex sensitivity (BRS) in chronic hypertensive pregnant women (CH), normotensive pregnant (PRE) and non-pregnant (NPRE) women. In addition to the traditional 'sequence method' we used joint symbolic dynamics (JSD). BRS was significantly reduced in all pregnancies compared with NPRE (p < 0.00001) but there was no significant difference between CH and PRE. Contrary, the JSD measures revealed significant differences (p < 0.00001) in the heart rate and blood pressure interactions between PRE and CH. In conclusion, JSD measures uncovered a different gestation related adaptation of autonomic regulation in women with chronic.

Adult↗

Gestational regulation of the gene expression of C-type natriuretic peptide in mouse reproductive and embryonic tissue.

C-Type natriuretic peptide (CNP) is a vasoactive hormone and the endothelial component of the natriuretic peptide system. We examined the expression of CNP in mouse reproductive organs and embryos at different stages of gestation. Pregnant mice were killed and embryos were dissected on gestational days 9.5, 12.5, 15.5, 18.5 postconceptionem (pc) and at term. Nonpregnant mice were used as controls. Total RNA was isolated from placenta, ovaries, myometrium and from head and trunk of embryos and neonates. CNP-mRNA was quantified by ribonuclease-protection assay (RPA). Uterine CNP-mRNA concentrations increase during pregnancy up to the sevenfold concentration, whereas in the ovaries these levels decrease to 10% compared to nonpregnant controls. In the placenta, a peak of CNP expression has been observed around day 15.5 pc, whereby placenta showed the strongest CNP signals. CNP-mRNA concentrations in embryos are gestational age-dependent with a high level at day 9.5 pc in head and trunk. These results indicate that CNP has a regulatory function in pregnancy and embryonic development.

Animals↗

Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression.

BACKGROUND: Regression of left ventricular hypertrophy (LVH) after surgical correction for aortic stenosis is not fully understood on the molecular level. The aim of this study was to examine whether there is an association between LVH regression and extracellular matrix (ECM) gene expression. METHODS AND RESULTS: A standard model of controlled LVH induction by supracoronary banding (A=baseline) was applied in 44 growing sheep (age, 6 to 8 months). Surgical correction to release the pressure gradient was performed 8.3+/-1 months later (B). The animals were killed after another 10.1+/-2 months (C). At all time points, hemodynamic evaluations and quantitative analysis of mRNA and protein expression for matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) was performed. Left ventricular mass index was 82+/-21 (A) versus 150+/-33 (B), P<0.01, and 78+/-18 g/m(2) (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter index was 9.1+/-1.2 (A) versus 12.3+/-1.4 (B), P<0.01, and 8.4+/-1.3 micrometer/m(2) (C), P<0.01. In parallel to the development of LVH at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3. After surgical correction (C), there was a complete regression of gene expression to baseline measures. CONCLUSIONS: Controlled induction of compensated LVH leads to significant increase in ECM gene expression. The regression of LVH after surgical therapy is associated with complete regression of ECM gene expression. However, no cause-and-effect relation could be demonstrated.

Animals↗

Impaired angiotensin II regulation of renal C-type natriuretic peptide mRNA expression in experimental diabetes mellitus.

OBJECTIVE: Abnormalities in the regulation of natriuretic peptides (NP) associated with major diseases such as hypertension, heart failure, and diabetes mellitus (DM) have been reported. We investigated levels of mRNA for the vasodilator C-type natriuretic peptide (CNP) in the renal cortex of streptozotocin (STZ)-diabetic rats and the influence of an angiotensin II inhibition. METHODS: DM was induced in Wistar rats by a single STZ injection. Rats were kept for 12 weeks. Additionally, the influence of the ACE inhibitor ramipril (Ram: 3 mg/kg/day) and the AT1 receptor antagonist losartan (Los: 20 mg/kg/day) on CNP expression in the STZ-diabetic and control groups was studied (each group n=6). Animals were characterized by their mean arterial blood pressure, plasma glucose levels, and renal function (each group n=9). After extraction of total renal cortical RNA, CNP expression was analyzed by Northern blots. RESULTS: Renal function was impaired in STZ-diabetic rats which has been improved by Ram and Los treatment. Untreated STZ-diabetic rats showed no difference in renal CNP expression compared to untreated controls. Ram and Los treatments led to an increase in renal cortical CNP mRNA in both diabetic and non-diabetic rats. This effect was weaker in STZ-diabetic rats (Ram: control 5.4-fold, STZ 3.5-fold; Los: control 4.2-fold, STZ 1.9-fold). CONCLUSION: These results clearly demonstrate a direct regulatory effect of the renin-angiotensin system (RAS) on renal mRNA levels of CNP. We suggest that RAS inhibition not only prevents the generation of angiotensin II (AngII) but also leads to a stimulation of CNP expression. We conclude that AngII suppresses CNP expression via the AT1 receptor and this mechanism is impaired in STZ-diabetic rats.

Angiotensin II↗

Genetic deletion of angiotensin AT2 receptor leads to increased cell numbers in different brain structures of mice.

Angiotensin II (Ang II) is a potent vasoactive peptide and displays growth factor-like properties. Different high-affinity Ang II receptor subtypes (AT1A, AT1B and AT2) have been cloned. They are expressed in various brain structures. Additionally, it has been assumed that Mas could interact directly or indirectly with the renin-angiotensin system. The AT1 receptor mediates pressor and mitogenic effects of Ang II, whereas physiological function and signaling mechanisms of the AT2 receptor remain poorly understood. Recent reports have shown that Ang II could mediate apoptosis through AT2 receptors. Since the AT1A, AT2 and Mas knockout mice provide new tools for uncovering potential actions of Ang II, the cell number in different brain structures of male adult wild-type mice and mice deficient for AT1A, AT2 or Mas was evaluated to get more insight into the role of Ang II in central nervous system development. In nearly all investigated brain structures (cortex, hippocampus, amygdala, thalamus), the cell number was significantly higher in AT2-deficient mice in comparison to wild-type mice. To the contrary, in AT1A-deficient mice the cell number was significantly less than in controls in the lateral geniculate and the medial amygdaloid nucleus. However, cell numbers were not changed in Mas-knockout mice compared to their wild-types. These results show the contrary effects of both angiotensin receptors on cell growth and represent the first demonstration of their action on neuronal cell development evidenced in the adult mouse brain.

Angiotensin II↗

Nature of the Stranski-Krastanow transition during epitaxy of InGaAs on GaAs.

We report first quantitative measurements by energy-selected imaging in a transmission electron microscope of In segregation within an uncapped islanded In0.25Ga0.75As layer grown epitaxially on GaAs. This layer has the lowest In concentration at which islanding occurs and, then, only after a flat approximately 3 nm alloy layer has been formed. In buildup by segregation at the surface of this initial flat layer is considered the driving force for islanding and, importantly, the segregation process introduces the characteristic delay seen before the Stranski-Krastanow transition. We observe strong inhomogeneous In enrichment within the islands (up to x(In) approximately 0.6 at the apex) and a simultaneous In depletion in the remaining flat layer.

Journal Article↗

Extracellular matrix gene expression correlates to left ventricular mass index after surgical induction of left ventricular hypertrophy.

The cardiac extracellular matrix (ECM) is a dynamic entity maintaining the structural and functional properties of the myocardium. Little is known about alterations in ECM regulation during controlled induction of compensated left ventricular hypertrophy (LVH) using experimental aortic stenosis. Fifteen growing sheep received supra-coronary banding at an age of 7 +/- 1 months whereas 10 age-matched sheep served as the control group (C). Explantation of the hearts was performed 8.3 +/- 1 months after banding. Gene sequences for sheep matrix metalloproteinase (MMP)-1,-2,-3,-9 and tissue inhibitors (TIMP)-1,-2,-3 were isolated and cloned. Then mRNA and protein gene expression analyses were performed. Concentric LVH with no evidence of heart failure was diagnosed at explantation. Left ventricular mass index (LVMI) was 150 +/- 33 g/m2 (LVH) versus 88 +/- 23 (C) and 82 +/- 21 (baseline) (p < 0.01 versus LVH). Parallel to LVH there was a significant increase in mRNA and protein expression for MMP-1,-2,-3, -9 and for TIMP-1,-2 whereas there was a significant decrease in TIMP-3 gene expression. A close correlation between changes in LVMI and ECM gene expression was found. Compensated LVH goes along with a significant modification of MMP and TIMP gene expression. Alterations in ECM gene expression may be part of the adaptive process during left ventricular remodeling.

Animals↗