Biomedical subjects

Thomas Walther

Publications and source records attributed to Thomas Walther.

At least 55 records · Page 3Linked to original sources

PubMed2005

Combustion exhaust measurements of nitric oxide with an ultraviolet diode-laser-based absorption sensor.

A diode-laser-based sensor has been developed for ultraviolet absorption measurements of the nitric oxide (NO) molecule. The sensor is based on the sum-frequency mixing (SFM) of the output of a tunable, 395-nm external-cavity diode laser and a 532-nm diode-pumped, frequency-doubled Nd:YAG laser in a beta-barium borate crystal. The SFM process generates 325 +/- 75 nW of ultraviolet radiation at 226.8 nm, corresponding to the (v' = 0, v" = 0) band of the A2Sigma+-chi2II electronic transition of NO. Results from initial laboratory experiments in a gas cell are briefly discussed, followed by results from field demonstrations of the sensor for measurements in the exhaust streams of a gas turbine engine and a well-stirred reactor. It is demonstrated that the sensor is capable of fully resolving the absorption spectrum and accurately measuring the NO concentration in actual combustion environments. Absorption is clearly visible in the gas turbine exhaust even for the lowest concentrations of 9 parts per million (ppm) for idle conditions and for a path length of 0.51 m. The sensitivity of the current system is estimated at 0.23%, which corresponds to a detection limit of 0.8 ppm in 1 m for 1000 K gas. The estimated uncertainty in the absolute concentrations that we obtained using the sensor is 10%.

Journal Article↗

PubMed2005

Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodents.

Biochemical analysis revealed that angiotensin-converting enzyme related carboxy-peptidase (ACE2) cleaves angiotensin (Ang) II to Ang-(1-7), a heptapeptide identified as an endogenous ligand for the G protein-coupled receptor Mas. No data are currently available that systematically describe ACE2 distribution and activity in rodents. Therefore, we analyzed the ACE2 expression in different tissues of mice and rats on mRNA (RNase protection assay) and protein levels (immunohistochemistry, ACE2 activity, western blot). Although ACE2 mRNA in both investigated species showed the highest expression in the ileum, the mouse organ exceeded rat ACE2, as also demonstrated in the kidney and colon. Corresponding to mRNA, ACE2 activity was highest in the ileum and mouse kidney but weak in the rat kidney, which was also confirmed by immunohistochemistry. Contrary to mRNA, we found weak activity in the lung of both species. Our data demonstrate a tissue- and species-specific pattern for ACE2 under physiological conditions.

Angiotensin-Converting Enzyme 2↗

PubMed2005

Anomalous origin of the right coronary artery from the pulmonary artery combined with aortic valve stenosis.

We report the case of a 41-year-old patient presenting with anomalous of origin of the right coronary artery from the pulmonary artery (ARCAPA) and severe aortic valve stenosis. Surgical correction was performed by partial (T-shaped) sternotomy. After replacing the bicuspid aortic valve, the right coronary artery ostium was directly reimplanted into the aortic root. The main pulmonary artery was reconstructed using an autologous pericardial patch. Postoperative recovery was uneventful. Four cases involving an association of the bicuspid aortic valve and ARCAPA have been reported in the literature. This potential relationship should be considered whenever diagnosing a bicuspid aortic valve.

Abnormalities, Multiple↗

PubMed2005

Beating heart off-pump myocardial revascularization in an infant.

A 6-week-old patient weighing 4 kg was admitted for surgical correction of anomalous left coronary artery from the pulmonary artery. Reimplantation of the coronary artery with cardiopulmonary bypass was impossible because the patient also had hereditary spherocytosis, which put him at risk for hemolytic anemia. Thus, closure of the left main stem and left internal mammary artery-left anterior descending coronary artery bypass grafting were performed successfully with the heart beating.

Coronary Artery Bypass, Off-Pump↗

PubMed2005

Facilitated minimally invasive left ventricular epicardial lead placement.

PURPOSE: Atrial-synchronized biventricular pacing is an effective treatment option in patients with heart failure and interventricular conduction delay. Owing to a failed transvenous implantation in some patients, the left ventricular (LV) lead has to be placed surgically, usually by an anterolateral thoracotomy. We used a novel malleable epicardial lead placement tool (Epicardial Lead Implant Tool, Model 10626; Medtronic, Minneapolis, MN) that facilitates lead placement on the posterior aspect of the LV through an anterolateral minithoracotomy. DESCRIPTION: The tool consists of a malleable steel shaft with distal gripping tongs for the epicardial lead. Proximally, a thumbwheel and an actuator button allow fixation and release of the lead on the myocardium. EVALUATION: We used this tool in 7 patients through an anterolateral minithoracotomy. All patients had a safe, successful, and rather short procedure. No scopes were required. CONCLUSIONS: Epicardial LV lead placement through an anterolateral minithoracotomy is facilitated by using the Lead Implant Tool. Lead placement is achieved by the malleable shaft design, which enables perpendicular implantation of the lead pad on the posterior LV surface with an anterolateral approach.

Defibrillators, Implantable↗

PubMed2005

Impact of off-pump coronary bypass grafting on the prevalence of adverse perioperative outcome in women undergoing coronary artery bypass grafting surgery.

BACKGROUND: Female gender has been associated with a high prevalence of perioperative morbidity and mortality in coronary artery bypass grafting surgery (CABG). We attempted to determine a potential benefit of off-pump CABG as compared with on-pump CABG (OPCAB) with regard to perioperative outcome in female patients. METHODS: Data were prospectively gathered on 2,182 consecutive female patients undergoing CABG either with or without cardiopulmonary bypass from 1996 to 2001. The associations between OPCAB surgery in addition with 22 further preoperative patient-related or treatment-related variables and 26 perioperative outcome variables were assessed with multivariable logistic regression analysis. RESULTS: One hundred fifty-two (7.0%) female patients underwent OPCAB surgery during the study period. Women undergoing OPCAB had higher ejection fractions and received fewer coronary artery bypass grafts than CABG patients. Surgery using OPCAB was associated with shorter hospital stays, less bleeding, less transfusion requirements, and lower mortality than CABG. Furthermore, OPCAB surgery was independently associated with a lower prevalence of high perioperative transfusion requirement, postoperative respiratory insufficiency, postoperative renal insufficiency, and dialysis. Prevalence of postoperative blood loss of at least 500 mL was significantly higher after OPCAB surgery. CONCLUSIONS: OPCAB in female patients undergoing coronary artery bypass surgery is safe and seems to be beneficial with regard to perioperative outcome as compared with conventional on-pump CABG. For that reason, off-pump surgery may be an effective method of lowering morbidity and mortality in these relatively high-risk patients.

Aged↗

PubMed2005

Clinical experience with stentless mitral valve replacement.

BACKGROUND: Our aim is to describe the clinical experience with stentless mitral valve (SMV) replacement with special focus on the functionality of the SMV. METHODS: Fifty-two patients (68 +/- 8.5 years old; 36 female) have been prospectively evaluated since August 1997. The chordally supported SMV (Quattro) was implanted for mitral stenosis (n = 26), severe incompetence (n = 17), or mixed lesion (n = 9). Preoperative New York Heart Association class was 3.1 +/- 0.6. Twenty patients received additional intraoperative ablation therapy. Mean follow-up is 37.3 +/- 18.7 months (range, 1 to 65). RESULTS: Surgery was performed using conventional sternotomy (33) or anterolateral minithoracotomy (19). Atrial rhythm was reestablished in 17 of 20 patients. Six patients operated on early in this series required reoperation, 2 for paravalvular leakage, 2 for functional stenosis, 1 with pannus formation due to underlying rheumatoid disease, and 1 for papillary flap rupture after 5.1 years. Mortality was 1 perioperative (1.9%, nonvalve related) and 1 after reoperation due to multiorgan failure. During late follow-up (30 +/- 7 months postoperatively) 5 patients died of noncardiac causes. Regular echocardiographic control revealed good SMV function (maximum transmitral blood flow velocity 1.7 +/- 0.2 m/s; mean transmitral pressure gradient 3.9 +/- 1.2 mm Hg) and well-preserved ejection fraction postoperatively as well as at most recent follow-up. CONCLUSIONS: The clinical experience after 5.5 years of SMV implantation is promising. Preservation of annuloventricular continuity is advantageous. However, long-term durability remains to be proved.

Aged↗

PubMed2005

Redo minimally invasive direct coronary artery bypass grafting.

BACKGROUND: Conventional redo coronary artery bypass grafting is associated with an increased risk of mortality and morbidity as a result of manipulation of patent grafts, mediastinitis, and the presence of pericardial adhesions. Minimally invasive direct coronary artery bypass grafting may be an alternative approach in selected patients. METHODS: From January 1997 to October 2003, 46 patients (mean age, 66 +/- 7.4 years) underwent minimally invasive direct coronary artery bypass grafting using the left internal thoracic artery to the left anterior descending artery on the beating heart as a reoperation. Patients after previous cardiac operation by means of median sternotomy without use of the left internal thoracic artery presenting with a significant left anterior descending artery stenosis ("culprit lesion") were included. Predicted mortality was 13.6% (range, 2.4% to 72.8%) as calculated by the logistic Euroscore; ejection fraction was 0.531 (range, 0.14 to 0.81). Surgical results were analyzed for mortality, morbidity, duration of the procedure, hospital stay, and event-free survival. RESULTS: Mean operating time was 103 +/- 34 minutes. There were two in-hospital deaths (4.6%), one for malignant ventricular arrhythmia (Euroscore, 60.9%) and the second as a result of severe gastrointestinal bleeding (Euroscore, 29.2%). One patient (2.3%) was successfully reoperated on because of perianastomotic hematoma using the same approach after 6 days. Patients were discharged after 9.4 +/- 2.6 days. There were no other serious adverse events, no stroke, and no myocardial infarction. During follow-up (37 +/- 21 months, complete in 92.1%), 1 patient experienced angina and 6 patients died. The actuarial 4-year survival is 74.8% (95% confidence interval, 51% to 92%), and the actuarial 4-year event-free survival including freedom from angina, major adverse cardiac events, and reintervention is 81% (95% confidence interval, 54% to 97%). CONCLUSIONS: Minimally invasive direct coronary artery bypass grafting can be considered as an alternative approach for redo coronary artery bypass grafting in selected patients.

Aged↗

PubMed2005

Elevated NT-ProBNP levels in patients with increased left ventricular filling pressure during exercise despite preserved systolic function.

BACKGROUND: The role of brain natriuretic peptides in the detection of mild forms of isolated diastolic dysfunction is still uncertain. We therefore investigated the plasma levels of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with heart failure symptoms during exercise, despite preserved systolic cardiac function. METHODS AND RESULTS: Fifteen control subjects and 15 symptomatic patients with preserved left ventricular ejection fraction of > or =50%, near normal Doppler echocardiographic indices, and left and right heart catheter indices at rest but increased filling pressures during exercise were studied. Plasma NT-proBNP levels and surrogate parameters of diastolic function were determined simultaneously. The median NT-proBNP plasma level was elevated (median, 145.2 pg/mL [range, 69.7-273.4 pg/mL] vs 38.3 pg/mL [range, 22.1-64.7 pg/ml]; P < .0001) in patients with increased filling pressure during exercise and correlated strongly with the pulmonary capillary wedge pressure (r = 0.78; P < .001). CONCLUSION: NT-proBNP levels are increased in patients with increased filling pressures during exercise and useful for the detection of diastolic dysfunction in patients with exertional dyspnea.

Adult↗

PubMed2005

Morphological, electrophysiological and coupling characteristics of bone marrow-derived mononuclear cells-an in vitro-model.

OBJECTIVE: Transplantation of bone marrow-derived mononuclear cells (BMC) may be suitable to prevent myocardial remodeling and improve left ventricular function after myocardial infarction. However, it is unknown whether or not cardiomyocytes and BMCs can form functioning cell-to-cell coupling and develop adequate electrophysiological properties. METHODS: BMCs were isolated from minipig leg bones, treated with 5-azacytidine (10 microM) for 24 h, cultured for 7 days and labeled with a fluoroscopic dye (DIL). BMCs were cocultured with spontaneously beating cardiomyocytes of neonatal rats. On days 4, 7 and 14 cocultured cells were analyzed. Immunhistochemistry (Connexin 43, alpha-actinin) was used to assess cardiomyogenic differentiation. Action potential characteristics were recorded in whole cell patch clamp mode and to investigate intercellular communication a second gap junction permeable fluoroscopic dye was brought into BMCs by microinjection (Lucifer yellow, LY). RESULTS: From day 7 in coculture BMCs beated synchronously with neonatal rat cardiomyocytes. On day 14, 55.9% of BMCs expressed alpha-actinin and 98.3% were positive for gap junction protein connexin 43. BMC action potential duration (APD90) was mean 11.1 ms with dV/dt(max) of 26.8 V/s and similar to atrial cardiac type. However, microinjection of LY revealed only little dye transfer into adjacent rat cardiomyocytes. CONCLUSIONS: Cocultured BMCs have the potential for early expression of muscle specific proteins in about 60% after 14 days and for cardiac gap junction proteins. Synchronous beating indicates an effective electromechanical coupling. In this heterologous setting we could prove only weak metabolic coupling.

Actinin↗

PubMed2005

A novel adhesion barrier facilitates reoperations in complex congenital cardiac surgery.

OBJECTIVE: Reoperations are associated with an increased surgical risk due to adhesions. We prospectively evaluated a bioresorbable membrane after surgery for congenital heart defects over a 3.5-year period. METHODS: The surgical membrane (CV Seprafilm, Genzyme, Cambridge, Mass) was applied in 350 of 1024 patients; 30 of them underwent reoperation and were evaluated in comparison to 10 random reoperated patients. Adhesions were evaluated using a subjective scoring system [1 (lowest tenacity) to 5 (highest tenacity)] and extent in percent at different regions of the heart. RESULTS: Patients were operated for atrioventricular septal defect (69), tetralogy of Fallot (65), functional single ventricle (75), valve surgery (48), ventricular septal defect (20), subaortic stenosis (17), hypoplastic left heart syndrome (17), and other diagnoses (39). Application of the surgical membrane was safe in all patients, without any infections. At reoperation patients received Glenn (14), total cavopulmonary connection (6), and others (10). Overall mortality was 2/350 (0.57%). There was a remarkable reduction in tenacity score (3.3 vs 4.3) and in the extent of adhesions (77.7% vs 86%). Duration of reoperation was significantly reduced. CONCLUSIONS: A bioresorbable surgical membrane leads to a significant reduction in the tenacity and amount of adhesions. It is recommended for general use whenever repeat operation is anticipated in congenital as well as in adult cardiac surgery.

Aortic Valve Stenosis↗

PubMed2005

Significant value of autopsy for quality management in cardiac surgery.

OBJECTIVE: With recent advances in diagnostic imaging, the value of autopsy has been called into question. The aim of our study was to assess the current impact of autopsy for early postoperative quality management in cardiac surgery. METHODS: Between 2000 and 2003, a total of 14,313 patients underwent cardiac surgery at our center. Of these, 898 patients (6.3%) died, and autopsy was performed in 468 cases (52.1%). Data from clinical and postmortem examination were prospectively analyzed regarding causes of death, postoperative complications, concomitant diseases, and surgery-associated pathologic findings. RESULTS: Mean age was 68.7 years. Mean survival was 13.9 postoperative days. On autopsy, causes of death were cardiac in 49.8% of cases (n = 233), respiratory in 8.3% (n = 39), cerebral in 6.4% (n = 30), abdominal in 4.7% (n = 22), multiorgan failure or sepsis in 14.9% (n = 70), pulmonary embolism in 6.6% (n = 31), procedure associated in 8.3% (n = 39), and others in 0.9% (n = 4). Discrepancies between clinical and postmortem determinations of cause of death were found in 108 cases (23.1%). These were acute myocardial infarction (n = 38), low cardiac output (n = 9), respiratory (n = 8), cerebral (n = 5), abdominal (n = 7), multiorgan failure or sepsis (n = 12), pulmonary embolism (n = 18), and procedure associated (11). Clinically unrecognized postoperative complications were found in 364 cases (77.8%). Unknown concomitant diseases were found in 464 cases (99.1%), with potential therapeutic relevance in 90 cases (19.2%). In 85 cases (18.2%), autopsy examination revealed 96 premortem unrecognized surgery-associated pathologic findings. CONCLUSION: A high overall discrepancy rate between premortem and autopsy diagnoses was recognized. Autopsy revealed clinically relevant information in a significant number of cases. Therefore autopsy remains essential for quality assessment in perioperative treatment.

Aged↗

PubMed2005

Ablation of atrial fibrillation and esophageal injury: effects of energy source and ablation technique.

OBJECTIVE: The aim of this study was the evaluation of histologic changes induced on the esophagus by surgical ablation therapy for atrial fibrillation. METHODS: Experiments were performed on 39 sheep. Circular lesions were created endocardially or epicardially in the left atrium and at the pulmonary veins by using different energy sources: cryoablation, microwave, laser, and unipolar or bipolar radiofrequency. Temperatures inside the esophagus were measured, and esophageal tissue was investigated macroscopically and histopathologically. RESULTS: Esophageal damage was seen histologically in 24 of 39 cases. The epithelium was intact in all cases. Unipolar radiofrequency induced the most intensive esophageal lesions in 4 of 6 cases. The affected areas were small (1.56-3.01 mm) but reached deep into the tissue. Endocardial cryoablation resulted in wider lesions (2.01-8.54 mm), which were intensive in only 2 of 6 cases. Epicardial cryoablation and bipolar radiofrequency induced wide (1.11-6.8 mm) but mainly mild alterations. Endocardial and epicardial microwave energy affected the esophagus in single cases, and lesions were small (0.97-2.81 mm). Only in 1 case did laser energy induce a moderate alteration (5.30 mm) of the esophageal wall. CONCLUSIONS: Esophageal alterations were found in numerous cases. However, marked lesions were especially induced by endocardial unipolar radiofrequency and cryoablation.

Animals↗

PubMed2005

Facilitated MIDCAB using a magnetic coupling device.

A 59-year-old male with chronic occlusion of the left anterior descending coronary artery underwent a minimally invasive direct coronary artery bypass procedure using the second generation of a magnetic anastomotic coupling device. Postoperative angiogram demonstrated excellent patency and flow.

Anastomosis, Surgical↗

PubMed2005

Central angiotensin II controls alcohol consumption via its AT1 receptor.

Pharmacological and genetic manipulations of the renin-angiotensin system (RAS) have been found to alter the voluntary consumption of alcohol. Here we characterize the role of central angiotensin II (Ang II) in alcohol intake first by using transgenic rats that express an antisense RNA against angiotensinogen and consequently have reduced Ang II levels exclusively in the central nervous system [TGR(ASrAOGEN)680]. These rats consumed markedly less alcohol in comparison to their wild-type controls. Second, Spirapril, an inhibitor of the angiotensin-converting enzyme (ACE), which passes the blood-brain barrier, did not influence the alcohol consumption in the TGR(ASrAOGEN)680, but it significantly reduced alcohol intake in wild-type rats. Studies in knockout mice indicated that the central effect of Ang II on alcohol consumption is mediated by the angiotensin receptor AT1 whereas the AT2 receptor and the bradykinin B2 receptor are not involved. Furthermore, the dopamine concentration in the ventral tegmental area (VTA) is markedly reduced in rats with low central Ang II, strengthening our hypothesis of a role of dopaminergic transmission in Ang II-controlled alcohol preference. Our results indicate that a distinct drug-mediated control of the central RAS could be a promising therapy for alcohol disease.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2005

The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice.

Recently, we demonstrated that the endothelium-dependent vasodilator effect of angiotensin(1-7) in the mouse aorta is abolished by genetic deletion of the G protein-coupled receptor encoded by the Mas protooncogene. To circumvent the limitations posed by the possible metabolism of Ang(1-7) in this vessel, in this work we studied the mechanism underlying the vasorelaxant effect of AVE 0991, a nonpeptide mimic of the effects of Ang(1-7), using wild-type and Mas-deficient mice. Ang(1-7) and AVE 0991 induced an equipotent concentration-dependent vasodilator effect in aortic rings from wild-type mice that was dependent on the presence of endothelium. The vasodilator effect of Ang(1-7) and AVE 0991 was completely blocked by 2 specific Ang(1-7) receptor antagonists, A-779 and D-Pro-Ang(1-7), and by inhibition of NO synthase with L-NAME. Moreover, in aortic rings from Mas-deficient mice, the vasodilator effect of both Ang(1-7) and AVE 0991 was abolished. In contrast, the vasodilator effect of acetylcholine and substance P were preserved in Mas-null mice. In addition, the vasoconstriction effect induced by Ang II was slightly increased, and the vasodilation induced by the AT2 agonist CGP 42112A was not altered in Mas-deficient mice. Our results show that Ang(1-7) and AVE 0991 produced an NO-dependent vasodilator effect in the mouse aorta that is mediated by the G protein-coupled receptor Mas.

Angiotensin I↗

PubMed2005

Longitudinal analysis of heart rate variability in chronic hypertensive pregnancy.

In the US, it is currently estimated that 3% of pregnant women have chronic hypertension, or more than 100,000 pregnant women each year. The aim of our study was to investigate the adaptation of autonomic control during pregnancy based on heart rate variability analysis and to determine whether chronic hypertension during pregnancy has an impact on this adaptation. Sixteen pregnant women with chronic hypertension (CH group; mean age, 30 years; range, 25-33 years) and 35 healthy pregnant women serving as controls (CON group; mean age, 28 years; range, 24-30 years) were recruited for this longitudinal study. Beginning at the 20th week of pregnancy, the women were monitored every 4th week until delivery. For the analysis of heart rate variability, Portapres signals (200 Hz) were recorded for 30 min under resting conditions. Women in the CH group had significantly elevated blood pressure compared to controls (CON, 111 mmHg [105-132]; CH, 140 mmHg [132-148]; p<0.001). An increased heart rate was found in both groups during the second half of pregnancy. Consequently, decreased heart rate variability was observed, but was more pronounced in the CON group. There was a shift in the frequency bands indicated by an elevation of the low-to-high frequency ratio (LF/HF) in both groups due to a decrease in HF, and thus a significant increase in LFn (LF power in normalized units). However, VLF (power of very low frequency range) increased exclusively in the CON pregnancies. Our data showed no significant difference in heart rate variability between the subjects of the CH and CON groups. Longitudinal variations were detectable in normal pregnancies and also, albeit to a lesser degree, in chronic hypertensive pregnant women. Thus, our data indicate that patients with long-term hypertension are still able to respond to the physiological changes occurring during pregnancy.

Adult↗

PubMed2005

Angiotensin AT2 receptor deficiency after myocardial infarction: its effects on cardiac function and fibrosis depend on the stimulus.

Hearts of normotensive angiotensin II type 2 receptor (AT2)-deficient mice do not develop fibrosis after angiotensin II-induced chronic hypertension. Thus, the goal of our study was to clarify whether AT2 knockouts (KOs) are also characterized by altered left ventricular (LV) function and modified remodeling of the extracellular matrix (ECM) after induction of myocardial infarction (MI). MI was induced in 5-mo-old female AT2-deficient mice and controls by occlusion of the left coronary artery. Time-matched sham-operated animals served as controls. After 48 h, the first sets of mice were hemodynamically characterized using a pressure-tip catheter (n = 8/group). We also obtained pressure volume loops using a microconductance catheter in additional sets of animals 3 wk after induction of MI (n = 7/group). Finally, the collagen index was illustrated by Sirius red staining and quantified by digital analysis. Whereas the LV function of sham-operated animals did not differ between both genotypes, the collagen index was 44% lower in KO animals. Forty-eight hours and 3 wk post-MI, systolic and diastolic LV function were impaired in both AT2-deficient and wild-type (WT) animals to the same extent by approx 45%. No differences were found between the two genotypes with respect to LV hypertrophy and the fibrosis index in the infarcted and noninfarcted areas 3 wk post-MI. While AT2-KO mice had less cardiac collagen content under basal conditions, the receptor deficiency had no significant influence on LV function at the two investigated time points after induction of MI or on the remodeling of ECM at the latter time point. Thus, hypertension-induced fibrosis is probably triggered by other control mechanisms than fibrosis induced by MI.

Animals↗