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Biomedical subjects

Thomas Walther

Publications and source records attributed to Thomas Walther.

At least 73 records · Page 4Linked to original sources
PubMed2005

Anastomotic devices for coronary artery bypass grafting.

With the advent of off-pump and minimally invasive coronary artery bypass grafting, efforts to facilitate construction of the graft to coronary anastomosis have increased. As a result, a number of anastomotic devices have been developed. While the ideal anastomotic device should be easy to use, produce a geometrically optimal anastomosis with minimal endothelial damage and minimal blood-exposed nonintimal surface, a number of design constraints apply. This review collects the available preclinical and clinical data for some of the devices, with special regard as to surgical outcome, patency rate and the need for additional perioperative anticoagulation treatment.

Anastomosis, Surgical↗
PubMed2005

Augmented reality for intraoperative guidance in endoscopic coronary artery bypass grafting.

Endoscopic bypass grafting can be complicated by limited intraoperative orientation. A method to overlay the preoperative model of the coronary tree on the live endoscopic images of the heart was therefore developed. The method is three-fold: (1) the three-dimensional (3D) model of the coronary tree is reconstructed from traditional angiograms; (2) preoperative images are registered with the intraoperative position of the patient in the operating room (OR); and (3) an iterative and interactive identification of clinically relevant landmarks within the operative field on the heart surface before their registration with the preoperative model of the coronaries. This algorithm allows one to compensate deformations (breathing, intraoperative heart shift) and leads to a precise overlay of the coronary network on the heart surface. For ergonomic reasons, the 3D model can be displayed directly within the visual field of any telesurgical master console. It thus provides an effective navigational aid to the surgeon similar to a global positioning system (GPS) in vehicles. Animal trials have been performed using the Da Vinci (Intuitive Surgical, Sunnyvale, CA, USA) teleoperated system to validate the method. Qualitative and quantitative analysis demonstrate the potential value during total endoscopic coronary artery bypass grafting.

Coronary Angiography↗
PubMed2005

Stentless mitral valve replacement by conventional and minimally invasive techniques.

Stentless mitral valve (SMV) replacement is an intriguing concept to preserve the functionality of the physiological mitral valve (MV). Beginning in August 1997 to date, 51 patients, 35 females and 16 males (age: 68.3+/-8.4 years), with severe MV disease (stenosis 25, incompetence 17, mixed lesion 9) received a chordally supported SMV. SMV implantation was performed using a conventional sternotomy in 32, or a minimally invasive lateral minithoracotomy approach in 19 of the patients. Mean valve size was 29+/-1.5 mm; cross-clamp duration was 81+/-33 min. The perioperative mortality rate was comparable to conventional MV repair or replacement. Regular echocardiographic control disclosed good SMV function (Vmax 1.7+/-0.2 m/s, Pmean 3.9+/-1.2 mmHg) and well-preserved ejection fraction postoperatively, as well as at their most recent follow-up visit. SMV implantation by way of a sternotomy or lateral minithoracotomy leads to preservation of the annulo-ventricular continuity and similar to physiological hemodynamics. However, long-term durability remains to be proven.

Aged↗
PubMed2004

Improvement of defective sarcoplasmic reticulum Ca2+ transport in diabetic heart of transgenic rats expressing the human kallikrein-1 gene.

The bradykinin-forming enzyme kallikrein-1 is expressed in the heart. To examine whether contractile performance and sarcoplasmic reticulum Ca2+ transport of the diabetic heart can be rescued by targeting the kallikrein-kinin system, we studied left ventricular function and sarcoplasmic reticular Ca2+ uptake after induction of streptozotocin-induced diabetes mellitus in transgenic rats expressing the human tissue kallikrein-1 gene. Six weeks after a single injection of either streptozotocin (70 mg/kg ip) or vehicle, left ventricular performance was determined using a Millar-Tip catheter system. The Ca2+-transporting activity of reticulum-derived membrane vesicles was determined in left ventricular homogenates as oxalate-supported 45Ca2+ uptake. Western blot analysis was used to quantify the reticular Ca2+-ATPase SERCA2a, phospholamban, and the phosphorylation status of the latter. Contractile performance and Ca2+ uptake activity were similar in nondiabetic wild-type and transgenic rats. Severely diabetic wild-type animals exhibited impaired left ventricular performance and decreased reticular Ca2+ uptake (-39% vs. wild-type rats, P<0.05, respectively). These changes were attenuated in diabetic transgenic rats that, in addition, exhibited a markedly increased phospholamban phosphorylation at the Ca2+/calmodulin kinase-specific site threonine17 (2.2-fold vs. diabetic wild-type rats, P<0.05). These transgene-related effects were abolished after treatment with the bradykinin B2 receptor antagonist icatibant (Hoe 140). The SERCA2-to-phospholamban ratio, phosphoserine16-phospholamban levels, and the apparent affinity for Ca2+ of the uptake reaction did not differ between the groups. Increasing the activity of the kallikrein-kinin system by expressing a human kallikrein-1 transgene protects rat heart against diabetes-induced contractile and reticular Ca2+ transport dysfunctions. An increased phosphorylation of the SERCA2 regulatory protein phospholamban at threonine17 via a B2 receptor-mediated mechanism is thereby involved.

Animals↗
PubMed2004

Prospectively randomized evaluation of stented xenograft hemodynamic function in the aortic position.

BACKGROUND: Standard stented aortic xenograft valves have not yet been compared regarding their hemodynamic function using a stratified intraoperative randomization protocol. METHODS AND RESULTS: 100 patients were prospectively included after intraoperative metric sizing of the decalcified aortic annulus. They received Mosaic (M) or Perimount (P) aortic valve replacement. Patient age was 73+/-5 years, 51 were female, and New York Heart Association (NYHA) functional class was 2.8+/-0.5. The 21-mm annulus group consisted of 5 (M)/7 (P) patients, the 23-mm annulus group of 20 (M)/20 (P), the 25-mm annulus group of 18 (M)/19 (P), and the 27-mm annulus group of 4 (M)/7 (P) patients, respectively. Hemodynamic function was evaluated using transthoracic echocardiography before discharge and at follow-up (438+/-352 days). Surgery was uncomplicated in all patients. Labeled valve sizes were 0.93 (M) and 1.05 (P) mm smaller than the annulus diameters (p=NS). In-hospital mortality was 5%, all nonvalve-related. Transvalvular blood flow velocities and transvalvular pressure gradients were significantly lower in the 25 P versus the 25 M group at baseline and in the 23 P and 25 P groups at follow-up. There was a significant regression of left ventricular mass index in all patients at follow-up. However, left ventricular mass regression was more pronounced after P aortic valve replacement. CONCLUSIONS: Labeled sizes of prosthetic heart valves implanted are smaller than the true aortic annulus. Both standard aortic xenografts compared in this prospectively randomized trial provide a sufficient hemodynamic and functional outcome.

Aged↗
PubMed2004

Nonpeptide AVE 0991 is an angiotensin-(1-7) receptor Mas agonist in the mouse kidney.

It has been described recently that the nonpeptide AVE 0991 (AVE) mimics the effects of angiotensin-(1-7) [Ang-(1-7)] in bovine endothelial cells. In this study, we tested the possibility that AVE is an agonist of the Ang-(1-7) receptor Mas, in vitro and in vivo. In water-loaded C57BL/6 mice, AVE (0.58 nmol/g body weight) produced a significant reduction in urinary volume (0.06+/-0.03 mL/60 min [n=9] versus 0.27+/-0.05 [n=9]; P<0.01), associated with an increase in urinary osmolality. The Ang-(1-7) antagonist A-779 completely blocked the antidiuretic effect of AVE. As observed previously for Ang-(1-7), the antidiuretic effect of AVE after water load was blunted in Mas-knockout mice (0.37+/-0.10 mL/60 min [n=9] versus 0.27+/-0.03 mL/60 min [n=11] AVE-treated mice). In vitro receptor autoradiography in C57BL/6 mice showed that the specific binding of 125I-Ang-(1-7) to mouse kidney slices was displaced by AVE, whereas no effects were observed in the binding of 125I-angiotensin II or 125I-angiotensin IV. Furthermore, AVE displaced the binding of 125I-Ang-(1-7) in Mas-transfected monkey kidney cells (COS) cells (IC50=4.75x10(-8) mol/L) and of rhodamine-Ang-(1-7) in Mas-transfected Chinese hamster ovary (CHO) cells. It also produced NO release in Mas-transfected CHO cells blocked by A-779 but not by angiotensin II type-1 (AT1) and AT2 antagonists. Contrasting with these data, the antidiuretic effect of AVE was totally blocked by AT2 antagonists and partially blocked (approximately 60%) by AT1 antagonists. The binding data, the results obtained in Mas-knockout mice and in Mas-transfected cells, show that AVE is a Mas receptor agonist. Our data also suggest the involvement of AT2/AT1-related mechanisms, including functional antagonism, oligomerization or cross-talk, in the renal responses to AVE.

Angiotensin I↗
PubMed2004

Angiotensin deficiency in mice leads to dilated cardiomyopathy.

To explore the role of angiotensin II, we assessed hemodynamics and cardiac function in angiotensinogen-deficient mice in comparison to wild-type animals. Left ventricular end-diastolic diameter and wall thickness were evaluated by echocardiography and systolic and diastolic left ventricular function by pressure-volume relations using a micro-conductance catheter. Compared to wild-type animals, the angiotensinogen-deficient mice were hypotensive and showed impaired systolic function. The hearts were dilated, demonstrated by echocardiography and by a right-ward shift of the pressure-volume loops, but end-diastolic pressure, isovolumic relaxation (tau) and diastolic stiffness were unchanged. Afterload, however, was reduced leading to maintained cardiac output. Although a blockade of the renin-angiotensin system via angiotensin converting enzyme inhibitors or angiotensin AT1 receptor antagonist is beneficial after cardiac failure, the absence of angiotensin peptides during the ontogenesis leads to dilated cardiomyopathy.

Angiotensin II↗
PubMed2004

The bradykinin B1 receptor contributes to the cardioprotective effects of AT1 blockade after experimental myocardial infarction.

OBJECTIVE: To investigate the role of the bradykinin B1 receptor (B1R) on the angiotensin receptor AT1 blockade-dependent cardioprotective effects, we studied the B1R regulation in wild-type rats treated with the AT1 antagonist, irbesartan (IRB), and also in transgenic rats with cardiac overexpression of the human AT1 (TGR-alphaMHCAT1) after induction of myocardial infarction (MI). In addition, we treated wild-type rats with IRB and/or the B1R antagonist, B9958, and determined the left ventricular (LV) function. METHODS: Untreated, IRB (50 mg/kg/day/p.o.), B9958 (0.1 mg/kg/48 h/s.c.), and IRB/B9958-treated Sprague-Dawley rats were submitted to a permanent occlusion of the left descending coronary artery. Six days and three weeks after induction of MI, the LV function was characterized by using a Millar-tip catheter. Myocardial AT1- and B1-mRNA expression were analyzed by RNase-protection assays, B1R protein density by immunohistochemistry. RESULTS: At both time points, LV function had improved by almost 50% after treatment with IRB but remained unchanged in TGR-alphaMHCAT1 after induction of MI compared to their untreated controls. The beneficial effect of IRB was reversed by co-treatment with B9958. The B1R antagonist treatment alone had no effect. A cross-talk between AT1 and B1R was also indicated by an up-regulation of B1R after treatment with IRB on protein and RNA level, while AT1 overexpression reduced B1R expression after induction of MI. CONCLUSION: These results indicate that the mechanisms of B1R regulation are influenced by the AT1 receptor. Thus, we are able to demonstrate for the first time that the B1R contributes to the cardio-beneficial effects of AT1 blockade.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Three-dimensional echocardiography for planning of mitral valve surgery: current applicability?

BACKGROUND: Two-dimensional transesophageal echocardiographic (2D TEE) assessment of the mitral valve requires mental integration of a limited number of 2D imaging planes. Structural display in three dimensions from any perspective may be of advantage to the surgeon for better judgment and planning. METHODS: Feasibility, accuracy, and limitations of preoperative three-dimensional transesophageal echocardiography (3D TEE) was assessed in 51 patients with mitral valve disease. The width of the anterior mitral valve was measured with either method and compared with the operative finding. Three-dimensional dynamic sequences of the reconstructed mitral valve were shown preoperatively to the surgeon and later compared with the intraoperative finding. RESULTS: The quality of the 3D reconstruction was graded as good in 25 patients (49.0%), fair in 16 patients (31.4%), and poor in 10 patients (19.6%) where atrial fibrillation did not allow ECG gating. Thirty-nine patients had successful mitral valve repair and twelve patients required valve replacement. Based on intraoperative findings, sensitivity for the diagnosis of mitral valve prolapse using 2D TEE and 3D TEE was 97.7% and 92.9% (p = ns) respectively and specificity was 100% by both methods. Sensitivity for the diagnosis of rupture of chordae tendineae using 2D TEE and 3D TEE was 92.3% and 30.8% respectively (p < 0.05) and specificity was 100% by both methods. CONCLUSIONS: Dynamic 3D echocardiography is feasible and can provide good insight into valvular motion and allows adequate preoperative planning when reconstruction is being considered. However dynamic 3D reconstruction is currently limited by the quality of the original 2D echo cross sectional images which can be adversely affected by minimal patient movements, breathing, or cardiac arrhythmia, thus limiting accuracy of the 3D TEE significantly compared with 2D TEE.

Aged↗
PubMed2004

Primary repair for aortic arch obstruction associated with ventricular septal defect.

BACKGROUND: The aim of the present study was to evaluate the current outcome and reoperation rate after applying a one-stage correction strategy for interrupted aortic arch (IAA) with ventricular septal defect (VSD) and also for aortic coarctation and hypoplastic aortic arch (CoA-HyAA) with VSD beginning September 1999. METHODS: Twenty-four consecutive patients with IAA (n = 12) or CoA-HyAA (n = 12) with VSD underwent early one-stage correction. Patients' mean age was 12 days (range, 2 to 188); mean weight was 3.6 kg (range, 2.1 to 7.3), 6 patients were less than 2.5 kg. Three IAA were type A, 5 type B1, 3 type B2, and 1 type C. Associated anomalies included a large VSD in all, left ventricular outlet tract obstruction in 5, transposition of the great arteries, aortopulmonary window, persistent truncus arteriosus, and double-outlet right ventricle in 1 patient. Selective brain perfusion through innominate artery and selective coronary perfusion through aortic root during aortic arch reconstruction was used in all patients. Mean follow-up was 2.2 +/- 0.9 years. RESULTS: There was no early, no late mortality, and no postoperative neurologic complications. Mean crossclamp duration was 72 +/- 32 minutes, lowest temperature 22.8 +/- 4 degrees C and selective brain and coronary perfusion duration was 34 +/- 13 minutes. Eighteen patients required delayed sternal closure at 1.7 days postoperatively. New perioperative management reduced the overall morbidity. Four patients after IAA plus VSD repair developed aortic arch restenosis and were successfully treated by balloon dilatation. One patient with d-TGA underwent right ventricular outflow tract reconstruction of right ventricular outlet tract obstruction 7 months after the initial repair. Pressure gradients across the anastomosis at most recent follow up were less than 10 mm Hg. All patients are asymptomatic and are developing normally. CONCLUSIONS: One-stage complete correction is feasible in newborns with aortic arch obstruction with VSD. Complex cardiac anatomy presents no additional risk for the procedure. The early one-stage correction yields excellent surgical results and good functional outcome.

Aorta, Thoracic↗
PubMed2004

Five-year results of 219 consecutive patients treated with extracorporeal membrane oxygenation for refractory postoperative cardiogenic shock.

BACKGROUND: Postcardiotomy cardiogenic shock occurs in approximately 1% of patients. We prospectively evaluated the early and long-term outcome as well as predictors of survival when using temporary extracorporeal membrane oxygenation (ECMO) support. METHODS: During 5 years 219 of 18150 patients (1.2%) undergoing cardiac surgery (coronary artery bypass grafting, n = 119; aortic valve replacement, n = 24; coronary artery bypass grafting and aortic valve replacement, n = 21; coronary artery bypass grafting and mitral valve replacement, n = 11; other procedures, n = 44) required temporary postoperative ECMO support. The ECMO implantation was performed through the femoral vessels or through the right atrium and ascending aorta. Additional intraaortic balloon counterpulsation was employed in 144 patients to improve coronary blood flow. RESULTS: Mean duration of ECMO support was 2.8 +/- 2.2 days. One hundred thirty-four patients (60%) were successfully weaned from ECMO. Of these, 52 patients (24%) were discharged from the hospital after 29.9 +/- 24 days. The main cause of death was myocardial failure. Five-year follow-up is 96% complete; 37 patients (74%) were alive with reasonable exercise capacity. CONCLUSIONS: Extracorporeal membrane oxygenation is an acceptable technique for short-term treatment of refractory postoperative low cardiac output. It can save the lives of a group of very high risk patients.

Aged↗
PubMed2004

On-pump versus off-pump coronary artery bypass grafting: impact on postoperative renal failure requiring renal replacement therapy.

BACKGROUND: Despite refinements in perioperative patient management postoperative renal failure requiring hemofiltration or dialysis is still a common complication after coronary artery bypass grafting associated with impaired patient outcome. METHODS: Prospective data on 9,631 patients receiving myocardial revascularization with (coronary artery bypass grafting [n = 8,870]) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting [n = 761]) between April 1996 and August 2001 were evaluated by univariate and multivariate logistic regression analysis. RESULTS: Overall prevalence of postoperative continuous renal replacement therapy was 4.1% (coronary artery bypass grafting, 4.3%; off-pump coronary artery bypass grafting, 1.8%; p = 0.001). Thirty of 40 selected preoperative and intraoperative patient and treatment related variables had a high association with the requirement for postoperative renal replacement therapy; fifteen of these variables were independent predictors in the whole study population. Off-pump coronary artery bypass surgery was identified as having a significantly lower predictive value for postoperative continuous renal placement therapy. In the subgroup of patients undergoing off-pump coronary artery bypass grafting surgery, a second multivariate logistic regression model revealed preoperative cardiogenic shock, urgent operation, intraoperative low cardiac output, and high transfusion requirement as independent predictors for postoperative renal replacement therapy. CONCLUSIONS: Patients with preoperative nondialysis dependent renal insufficiency are at a high risk for further decline in renal function requiring postoperative continuous renal replacement therapy. Off-pump coronary artery bypass surgery is associated with a lower prevalence of postoperative renal replacement therapy after coronary artery bypass grafting.

Aged↗
PubMed2004

A new cryoprobe for intraoperative ablation of atrial fibrillation.

We describe the use of a new argon cryoprobe (SurgiFrost) for isolated endocardial surgical ablation. A right lateral minithoracotomy and femoro-femoral cardiopulmonary bypass were applied. The basic mechanism of cryoablation is to remove heat from the targeted arrhythmogenic tissue followed by electrical isolation. In this first case of isolated treatment of atrial fibrillation using the new flexible SurgiFrost cryocatheter, we were able to perform pulmonary vein isolation reaching temperatures as low as -144 degrees C. The patient was discharged in sinus rhythm. This new argon cryoprobe represents an encouraging technology for the isolated endocardial as well as concomitant treatment of atrial fibrillation.

Atrial Fibrillation↗
PubMed2004

Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery.

BACKGROUND: Despite improved outcomes after cardiac operations, postoperative delirium remains a common complication that is associated with increased morbidity and prolonged hospital stay. METHODS: Univariate and multivariate predictors of postoperative delirium were determined from prospectively gathered data on 16,184 patients undergoing cardiac operations with cardiopulmonary bypass (conventional, n = 14,342) and without cardiopulmonary bypass (beating-heart surgery, n = 1847) between April 1996 and August 2001. Delirium was defined as a transient mental syndrome of acute onset characterized by global impairment of cognitive functions, a reduced level of consciousness, attentional abnormalities, increased or decreased psychomotor activity, and a disordered sleep-wake cycle. RESULTS: The overall prevalence of postoperative delirium was 8.4%. Of 49 selected patient-related risk factors and treatment variables, 35 were highly associated with postoperative delirium by univariate analysis. Stepwise logistic regression revealed the following variables as independent predictors of delirium: history of cerebrovascular disease, peripheral vascular disease, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction of 30% or less, preoperative cardiogenic shock, urgent operation, intraoperative hemofiltration, operation time of 3 hours or more, and a high perioperative transfusion requirement. Two variables were identified as having a significant protective effect against postoperative delirium: beating-heart surgery and younger patient age. CONCLUSIONS: Postoperative delirium is a common complication in cardiac operations. The increased use of beating-heart surgery without cardiopulmonary bypass may lead to a lower prevalence of this complication and thus improve patient outcomes.

Age Distribution↗
PubMed2004

Prevention of cardiac fibrosis and left ventricular dysfunction in diabetic cardiomyopathy in rats by transgenic expression of the human tissue kallikrein gene.

Diabetic cardiomyopathy includes fibrosis. Kallikrein (KLK) can inhibit collagen synthesis and promote collagen breakdown. We investigated cardiac fibrosis and left ventricular (LV) function in transgenic rats (TGR) expressing the human kallikrein 1 (hKLK1) gene in streptozotocin (STZ) -induced diabetic conditions. Six weeks after STZ injection, LV function was determined in male Sprague-Dawley (SD) rats and TGR(hKLK1) (n=10/group) by a Millar tip catheter. Total collagen content (Sirius Red staining) and expression of types I, III, and VI collagen were quantified by digital image analysis. SD-STZ hearts demonstrated significantly higher total collagen amounts than normoglycemic controls, reflected by the concomitant increment of collagen types I, III, and VI. This correlated with a significant reduction of LV function vs. normoglycemic controls. In contrast, surface-specific content of the extracellular matrix, including collagen types I, III, and VI expression, was significantly lower in TGR(hKLK1)-STZ, not exceeding the content of SD and TGR(hKLK1) controls. This was paralleled by a preserved LV function in TGR(hKLK1)-STZ animals. The kallikrein inhibitor aprotinin and the bradykinin (BK) B2 receptor antagonist icatibant reduced the beneficial effects on LV function and collagen content in TGR(hKLK1)-STZ animals. Transgenic expression of hKLK1 counteracts the progression of LV contractile dysfunction and extracellular matrix remodeling in STZ-induced diabetic cardiomyopathy via a BK B2 receptor-dependent pathway.

Animals↗
PubMed2004

Relation of ANP and BNP to their N-terminal fragments in fetal circulation: evidence for enhanced neutral endopeptidase activity and resistance of BNP to neutral endopeptidase in the fetus.

OBJECTIVES: To investigate the role of neutral endopeptidase in the turnover of atrial (ANP) and brain (BNP) natriuretic peptides and their N-terminal fragments in human fetal circulation. DESIGN: Retrospective case-control study. SETTING: Department of Obstetrics and Gynaecology, University of Leipzig, Germany. SAMPLE: Nine control pregnancies and nine pregnancies with rhesus isoimmunisation before and after intravascular transfusion. METHODS: Natriuretic peptides and N-terminal fragments in maternal and fetal blood were measured by radio-immunoassay. Neutral endopeptidase activity was determined by HPLC. MAIN OUTCOME MEASURES: Maternal and fetal plasma concentrations of ANP, NT-proANP, BNP, NT-proBNP as well as neutral endopeptidase activity. Ratios between mature peptide and N-terminal fragment. Feto-maternal ratio. RESULTS: Plasma NT-proANP concentrations are 11.7 times higher in fetal than in maternal circulation. The ANP concentration is only 1.8 times higher, probably due to doubled neutral endopeptidase activity. In contrast, both NT-proBNP and BNP are doubled in fetal plasma. Fetuses with Rh isoimmunisation had significantly higher NT-proBNP but not NT-proANP and neutral endopeptidase activity than controls. An additional volume load by intravascular transfusion did not influence N-terminal fragments or neutral endopeptidase activity. CONCLUSIONS: Our study is the first to determine NT-pro natriuretic peptide concentrations and neutral endopeptidase activity in human fetuses. The results show that increased fetal neutral endopeptidase activity shifts the ANP/NT-proANP but not the BNP/NT-proBNP ratio and that the shifted BNP/NT-proBNP ratio in fetuses with Rh isoimmunisation does not involve increased neutral endopeptidase activity. These findings point to a BNP degradation that is not dependent on neutral endopeptidase.

Atrial Natriuretic Factor↗
PubMed2004

Biochemical analysis of neutral endopeptidase activity reveals independent catabolism of atrial and brain natriuretic peptide.

Recent reports presented contradictory results regarding the catabolism of mature atrial (ANP) and brain (BNP) natriuretic peptides in circulation. Especially the role of neutral endopeptidase (NEP) in BNP degradation was conversely discussed. Our present in vitro-studies characterize the NEP-dependent metabolism of ANP and BNP in different tissues via HPLC-analysis using NEP-deficient mice and specific NEP inhibitors. Our results show a strong tissue-dependent degradation pattern of both peptides, which are not only due to the different NEP activities in these tissues. Whereas NEP rapidly degraded ANP, it had no influence in BNP-metabolism. Additional experiments with purified NEP confirmed this result. Moreover, we describe a degradation of ANP and BNP in NEP-deficient- and NEP-inhibited membranes. Consequently, we postulate the existence of at least one further natriuretic peptide (NP) degrading enzyme, which has not been characterized yet. Thus, the commonly accepted model of the natriuretic peptide system with NEP as the central degrading peptidase has to be partly revised. Moreover, the NEP-independent BNP degradation provides an effective means for achieving a beneficial BNP increase in cardiovascular pathology by inhibiting the assumed novel NP-degrading peptidase(s).

Animals↗