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Biomedical subjects

Thomas Walther

Publications and source records attributed to Thomas Walther.

At least 19 recordsLinked to original sources

Accelerated mitochondrial adenosine diphosphate/adenosine triphosphate transport improves hypertension-induced heart disease.

BACKGROUND: Strong evidence suggests that mitochondrial malfunction, which leads to disturbed energy metabolism and stimulated apoptosis, is a linchpin in the induction and manifestation of cardiac failure. An adequate exchange of ATP and ADP over the inner mitochondrial membrane by the adenine nucleotide translocase (ANT) is thereby essential to guarantee the cellular energy supply. METHODS AND RESULTS: To explore the effect of an ameliorated mitochondrial ATP/ADP transportation on cardiac dysfunction, we generated transgenic rats overexpressing ANT1 in the heart (ANT rats) and crossed them with renin-overexpressing rats (REN rats) suffering from hypertension-induced cardiac insufficiency. Cardiac-specific ANT1 overexpression resulted in a higher ATP/ADP transportation and elevated activities of respiratory chain complexes. Increased ANT activity in double-transgenic (ANT/REN) animals did not influence excessive hypertension seen in REN rats. Hypertension-induced cardiac hypertrophy in the REN rats was prevented by parallel ANT1 overexpression, however, and left ventricular function remarkably improved. The ANT1 overexpression led to a reduction in fibrosis and an improvement in cardiac tissue architecture. Consequently, the survival rate of ANT/REN rats was enhanced. Further investigations into the cardioprotective mechanism of ANT1 overexpression revealed improved mitochondrial structure and function and significantly reduced apoptosis in ANT/REN rats, shown by lowered cytosolic/mitochondrial cytochrome c ratio, reduced caspase 3 level, and prevented DNA degradation. CONCLUSIONS: Myocardial ANT1 overexpression protects against hypertension-induced cardiac pathology. Thus, the improvement in mitochondrial function may be a basic principle for new strategies in treating heart disease.

Adenine Nucleotide Translocator 1↗

Seven-year follow-up after minimally invasive direct coronary artery bypass: experience with more than 1300 patients.

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) for revascularization of the left anterior descending artery has become a routine operation. Here we present the experience after more than 1300 MIDCAB procedures with up to 7 years of follow-up. METHODS: All patients undergoing standard MIDCAB between 1996 and 2004 were included. Long-term follow-up information about health status, major cardiac and cerebral adverse events, and freedom of angina was collected annually by a questionnaire or personal contact. Preoperative, intraoperative, and postoperative data could be completed for all 1347 patients. Five-year follow-up was available for 450 patients and 7-year follow-up for 194 patients. RESULTS: Mean age was 63.2 years (range, 25 to 92 years) and mean ejection fraction was 0.61 +/- 0.14. In 23 patients (1.7%), intraoperative conversion to sternotomy or CPB, or both, was necessary. Early postoperative mortality was 0.8% (n = 11), and 0.4% (n = 5) had a perioperative stroke. A routine postoperative angiogram in 709 patients showed 95.6% early graft patency. Short-term target vessel reintervention was needed 55 patients (4.1%): 10 had percutaneous transluminal coronary angioplasty/stent and 45 had reoperation. A repeat angiogram at the 6-month follow-up was available in 350 patients and demonstrated 94.3% graft patency. Kaplan-Meier analysis revealed a 5-year survival of 91.9% (95% confidence interval [CI], 90.1% to 93.8%) and a 7-year survival of 89.4% (95% CI, 86.7% to 92.1%). The freedom of major adverse events and angina was 89.5% (95% CI, 87.4% to 91.5%) after 5 years and 83.3% (95% CI, 79.0% to 87.5%) after 7 years. CONCLUSIONS: MIDCAB can be safely performed with low postoperative mortality and morbidity. The excellent short-term and long-term survival as well as freedom from major adverse cardiac and cerebral events and angina compare favorably with stenting and conventional surgery.

Adult↗

Is parvovirus B19 the cause for autoimmunity against the angiotensin II type receptor?

Initial studies have demonstrated the significance of the agonistic angiotensin II receptor AT1 autoantibody (AT1-AA) in preeclampsia, although it is unclear what factors induce its generation. Since the epitope recognized by AT1-AA shares high homology with parvovirus B19 (PVB19) capsid proteins, we have investigated the relationship between the presence of AT1-AA in maternal circulation and PVB19 sero-prevalence in normal and abnormal pregnancy. We determined the parvovirus IgG sero-prevalence in normal pregnancies in the second trimester and those with abnormal uterine perfusion that are at risk for preeclampsia. Secondly, pregnancies at delivery with preeclampsia or intrauterine growth restriction were included. All women with normal perfusion were AT1-AA-negative and 80% were parvovirus-IgG-positive. Sixty-three percent of pregnancies with abnormal uterine perfusion were AT1-AA-positive and 71% IgG-positive. Fifty-two percent of the IgG-positive pregnancies in this subgroup were also AT1-AA-positive, and 9 of the 10 parvovirus IgG-negative women were AT1-AA-positive. In the third trimester, 87% of pregnancies with manifest disease were AT1-AA-positive and 58% IgG-positive. While 79% of the PVB19 IgG-positive pregnancies were also AT1-AA-positive, all parvovirus IgG-negative women were AT1-AA-positive. In all groups, AT1-AA activity did not differ between parvovirus IgG-negative and positive women. We find parvovirus IgG-positive pregnant women in all subgroups without relation to AT1-AA presence. This favors AT1-AA generation to be independent of epitope mimicry between parvovirus B19 capsid proteins and the AT1 receptor.

Animals↗

Minimally invasive transapical beating heart aortic valve implantation--proof of concept.

OBJECTIVE: To evaluate the feasibility of minimally invasive transapical beating heart aortic valve implantation (TAP-AVI) for high-risk patients with aortic stenosis. METHODS: TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Cribier-Edwards, Edwards Lifesciences, Irvine, CA, USA) was used. Thirty consecutive patients (82 +/- 5.1 years, 21 (70%) female) were operated from 02/06 until 09/06 at one center using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27 +/- 12%. RESULTS: Valve positioning was successful in 29 patients and one required early conversion to full sternotomy. Implantation (8 mm x 23 mm and 22 mm x 26 mm valves) was performed on the beating heart during brief periods of rapid ventricular pacing. ECC was applied in 13 patients. Neither coronary artery obstruction nor migration of the prosthesis was observed and all valves displayed good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 14 patients (trace in three, mild in nine and moderate in two). Three patients (10%) died, one on postoperative day (POD) three secondary to preoperative global myocardial failure and two on POD 18 and 86 due to abdominal complications. CONCLUSIONS: Minimally invasive beating heart TAP-AVI is feasible. Initial results are encouraging in view of the high-risk profile of the patients. Long-term studies as well as randomized protocols are required.

Aged↗

Narrow-linewidth, multi-Watt Yb-doped fiber amplifier at 1014.8 nm.

We report on an efficient, narrow linewidth, two-stage fiber amplifier at 1014.8 nm based on Yb-doped double-clad fibers. The fibers are cooled to liquid-nitrogen temperatures in order to suppress absorption at the operating wavelength. We achieved output powers of up to 5.0 W at a linewidth of less than 3 MHz by seeding the amplifier with the radiation from an external cavity diode laser.

Journal Article↗

Cardiac function and remodeling is attenuated in transgenic rats expressing the human kallikrein-1 gene after myocardial infarction.

Bradykinin coronary outflow, left ventricular performance and left ventricular dimensions of transgenic rats harboring the human tissue kallikrein-1 gene TGR(hKLK1) were investigated under basal and ischemic conditions. Bradykinin content in the coronary outflow of buffer-perfused, isolated hearts of controls and TGR(hKLK1) was measured by specific radioimmunoassay before and after global ischemia. Left ventricular function and left ventricular dimensions were determined in vivo using a tip catheter and echocardiography 6 days and 3 weeks after induction of myocardial infarction. Left ventricular type I collagen mRNA expression was analyzed by RNase protection assay. Compared to controls, basal bradykinin outflow was 3.5 fold increased in TGR(hKLK1). Ischemia induced an increase of bradykinin coronary outflow in controls but did not induce a further increase in TGR(hKLK1). However, despite similar unchanged infarction sizes, left ventricular function and remodeling improved in TGR(hKLK1) after myocardial infarction, indicated by an increase in left ventricular pressure (+34%; P<0.05), contractility (dp/dt max. +25%; P<0.05), and in ejection fraction (+20%; P<0.05) as well as by a reduction in left ventricular enddiastolic pressure (-49%, P<0.05), left ventricular enddiastolic diameter (-20%, P<0.05), and collagen mRNA expression (-15%, P<0.05) compared to controls. A chronically activated transgenic kallikrein kinin system with expression of human kallikrein-1 gene counteracts the progression of left ventricular contractile dysfunction after experimental myocardial infarction. Further studies have to show whether these results can be caused by other therapeutically options. Long acting bradykinin receptor agonists might be an alternative option to improve ischemic heart disease.

Animals↗

Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice.

Elevated central concentrations of the vasopressor octapeptide angiotensin (Ang) II increase the water intake in mammals. Recently, we showed that central AngII is also crucial in alcohol-consuming behavior. Since the heptapeptide AngIII, an AngII metabolite, is discussed to mediate AngII-related effects, we investigated water and alcohol consumption in mice, genetically deficient in aminopeptidase A (APA), a peptidase responsible for AngII conversion to AngIII. Sixteen male APA-deficient mice and their age matched wild-type controls were monitored on their water intake under basal conditions and total fluid and alcohol intake before and after social stress in a two-bottle free-choice paradigm. Alterations were connected to the regulation in activity of Ang-related peptidases (APA, ACE; ACE2) in brain regions involved in alcohol intake and peripheral organs. In comparison to their wild-type controls, APA-deficient mice drank significantly more water but not more alcohol at all investigated time points. A reduction in water intake, as observed in wild-type animals after social stress, did not occur in knockout mice. However, the reduction in alcohol consumption after social stress was significantly reduced in both strains. Alcohol consumption upregulated all three peptidases in the kidney, but not in lung. Notable, renal ACE2 activity was significantly higher in APA-deficient mice under basal condition. While the inhibition of AngII metabolism to AngIII does not influence the alcohol intake, water consumption in mice deficient for APA was significantly elevated. These differences induced by an altered AngII/AngIII ratio oppose the hypothesis that central AngII and AngIII act in a congruent pattern.

Alcohol Drinking↗

Emergency coronary artery bypass graft surgery for acute coronary syndrome: beating heart versus conventional cardioplegic cardiac arrest strategies.

BACKGROUND: Aim of this study was to compare the outcome of beating heart versus conventional coronary artery bypass graft (CABG) strategies in acute coronary syndromes for emergency indications. METHODS AND RESULTS: 638 consecutive patients with acute coronary syndrome (ACS) receiving emergency CABG surgery via midline sternotomy from January 2000 to September 2005 were evaluated. Propensity score analysis was used to predict the probability of undergoing beating heart (BH) (n=240) versus cardioplegic cardiac arrest (CA) (n=398) strategies. Patients presented with stable hemodynamics (n=531) or in cardiogenic shock (CS) (n=107). Hospital and follow-up outcome was compared by propensity score adjusted multiregression analysis. BH included 116 on-pump and 124 off-pump (OPCAB) procedures. There was a propensity to operate CS patients on the beating heart (multivariate odds ratio [OR], 3.8; P=0.001). Under stable hemodynamics significant predictors for BH selection were logEuroSCORE >20% (OR, 2.05), creatinine >1.8 mg/dL (OR, 4.12), complicated percutaneous coronary intervention (OR, 1.88), ejection fraction <30% (OR, 2.64), whereas left main disease (OR, 0.68), circumflex artery (OR, 0.32), and 3-vessel disease (OR, 0.67) indicated preference for cardioplegic arrest. Time from skin incision to culprit lesion revascularization was significantly reduced in BH patients. BH surgery led to a significant benefit in terms of less drainage loss, less transfusion requirement, less inotropic support, shorter ventilation time, lower stroke rate, and shorter intensive care unit stay. In CS, BH was associated with lower incidence of stroke, inotropic support, acute renal failure, new atrial fibrillation and sternal wound healing complications. In CS patients, hospital mortality rate was reduced when using beating heart strategies (P=0.048). Overall survival, major adverse cerebral and cardiovascular event rate, and repeated revascularization was comparable during a 5-year follow-up. CONCLUSIONS: Beating heart strategies are associated with an improved hospital outcome and comparable long-term results for high-risk patients presenting acute coronary syndrome with or without CS.

Adult↗

Patient prosthesis mismatch affects short- and long-term outcomes after aortic valve replacement.

OBJECTIVE: The aim of this study was to evaluate the impact of patient prosthesis mismatch (PPM) and additional risk factors on outcome after aortic valve replacement (AVR). METHODS: Four thousand one hundred and thirty-one patients who were operated between May 1996 and April 2004 were evaluated. One thousand eight hundred and fifty-six patients received bileaflet mechanical AVR and 2275 stented xenograft AVR. PPM was defined as severe if manufacturers effective orifice area (EOA) divided by body surface area (BSA) was <0.65 cm(2)/m(2) and as moderate in the range of 0.65-0.85 cm(2)/m(2). PPM, age, gender, EOA index, emergency indication for surgery (within 24h), EuroSCORE as well as requirement for additional procedures were tested. Univariate (Fisher's exact test) and multivariate logistic regression analysis as well as survival analysis (Kaplan-Meier) were performed. RESULTS: Severe PPM was present in 97 (2.4%) and moderate PPM in 1103 (26.7%) patients. PPM occurs more frequently with xenograft AVR. In-hospital mortality was 5.2% for severe, 10.6% for moderate and 6.9% with no PPM (p=0.018, OR 1.4). Moderate PPM was independently predictive for short- and long-term mortality. Further analysis revealed patient age >70 years (n=1589, p=0.002, OR 1.85), emergency indication (n=374, p<0.001, OR 4.4), EuroSCORE >10 (n=494, p<0.001, OR 4.7) and additional cardiac procedures (n=2049, p<0.001, OR 2.0) as predictors for adverse outcome after AVR. CONCLUSION: Severe PPM is rare; moderate PPM is present in a quarter of patients. PPM has a significant impact on short- and long-term mortality after AVR.

Aged↗

AT2 receptor-mediated vasodilation in the mouse heart depends on AT1A receptor activation.

Angiotensin (Ang) II type 2 (AT(2)) receptors are believed to counteract Ang II type 1 (AT(1)) receptor-mediated effects. Here, we investigated AT(2) receptor-mediated effects on coronary and cardiac contractility in C57BL/6 mice. Hearts were perfused according to Langendorff. Baseline coronary flow (CF) and left ventricular systolic pressure (LVSP) were 2.7 +/- 0.1 ml min(-1) and 111 +/- 3 mmHg (n = 50), respectively. Ang II (n = 14) concentration dependently decreased CF and LVSP, by maximally 41 +/- 4 and 25 +/- 3%, respectively (pEC(50)s 7.41 +/- 0.12 and 7.65 +/- 0.12). The AT(1) receptor antagonist irbesartan (n = 4) abolished all Ang II-induced changes, whereas the AT(2) receptor antagonist PD123319 (n = 6) enhanced (P < 0.05) the effect of Ang II on CF (to 59 +/- 1%) and LVSP (to 44 +/- 2%), without altering its potency. A similar enhancement was observed in the presence of nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester HCl (L-NAME; n = 4). On top of L-NAME, PD123319 no longer affected the response to Ang II (n = 4). The AT(2) receptor agonist CGP42112A (n = 4) did not affect CF or LVSP, nor did CGP42112A (n = 4) alter the constrictor response to the alpha(1)-adrenoceptor agonist phenylephrine. Furthermore, Ang II exerted no effects in hearts of AT(1A)(-/-) mice (n = 5), whereas its effects in hearts of AT(1A)(+/+) wild-type control mice (n = 7) were indistinguishable from those in hearts of C57BL/6 mice. In conclusion, Ang II exerts opposite effects on coronary and cardiac contractility in the mouse heart via activation of AT(1A) and AT(2) receptors. AT(2) receptor-mediated effects depend on NO and occur only in conjunction with AT(1A) receptor activation.

Angiotensin II↗

Transapical approach for sutureless stent-fixed aortic valve implantation: experimental results.

OBJECTIVE: Percutaneous aortic valve implantation has been performed in patients with severe aortic stenosis judged as nonsurgical candidates. We evaluated a facilitated transapical antegrade approach for potential use in surgical high-risk patients. METHODS: A pericardial xenograft fixed within a 23-mm stent (Cribier-Edwards aortic prosthesis, Edwards Inc., Irvine, CA, USA) was implanted using a transapical approach in fifteen 35-45 kg pigs. A limited or a full sternotomy was used to transapically introduce a crimped valve through a 24-F sheath. Deployments were performed on the beating heart either with ventricular unloading using femoro-femoral cardiopulmonary bypass (CPB) or rapid ventricular pacing (RVP), all under fluoroscopic and echocardiographic visualization. RESULTS: All valves were successfully deployed at the target site with acceptable visualization of the noncalcified annulus. Valve migration occurred in six procedures (three distal and three retrograde) secondary to inadequate reduction of ventricular output, unfavorable annular anatomy, excessive crimping of the valve, and dislodgement by the delivery balloon. Exact positioning of the valve into the target area was confirmed by autopsy at the end of the procedures. Paravalvular leak was noted in five implants. CONCLUSIONS: The transapical approach provides a safe, accurate, and effective route for facilitated antegrade delivery of a stent-fixed valve. Advanced stent design will lead to better stability of the implant and may minimize the risk of paravalvular leakage in future. Identifying the appropriate population for human feasibility trials remains a challenge.

Animals↗

Interactions between angiotensin ll and atrial natriuretic peptide in renomedullary interstitial cells: the role of neutral endopeptidase.

BACKGROUND/AIMS: Neutral endopeptidase (NEP) inhibition attenuates renal damage in the diabetic kidney, but little is known about the mechanisms of this renoprotective effect. METHODS: We examined the interaction between angiotensin II (Ang II) and atrial natriuretic peptide (ANP) under low (5 mM) and high (30 mM) glucose conditions, on cell proliferation and extracellular matrix (ECM) synthesis in renomedullary interstitial cells (RMICs) derived from wild-type (WT) and NEP-deficient (NEP-) mice. RESULTS: Under high glucose conditions, Ang II (10(-6)M) increased cell proliferation (control, 174.3 +/- 16.9; Ang II, 846.3 +/- 91.0 cpm/well) and ECM synthesis (control, 22.3 +/- 3.1; Ang II, 79.0 +/- 9.6 cpm/cell) in RMICs derived from WT and NEP- mice to a similar extent. ANP (10(-7)M) reduced Ang II-induced cell proliferation and ECM synthesis in RMICs derived from both strains, but more efficiently in RMICs derived from NEP- mice. The Ang II-induced cell proliferation and ECM synthesis was attenuated with AT1 receptor blockade, but more efficiently in RMICs-derived NEP- mice. CONCLUSIONS: This data shows that ANP and AT1 receptor blockade attenuate Ang II-induced RMIC proliferation and ECM synthesis more efficiently in the absence of NEP. These results support the concept that NEP inhibition is beneficial in attenuating abnormal cell growth and ECM metabolism associated with diabetic nephropathy.

Angiotensin II↗

Laser-assisted synthesis of Au-Ag alloy nanoparticles in solution.

By using laser-induced heating, we prepared Au-Ag nanoalloys via three different procedures: (i) mixture of Au nanoparticles and Ag(+) ions irradiated by a 532 nm laser, (ii) mixture of Au and Ag nanoparticles irradiated by a 532 nm laser, and (iii) mixture of Au and Ag nanoparticles irradiated by a 355 nm laser. Procedure i is advantageous for the production of spherical alloy nanoparticles; in procedures ii and iii, nanoalloys with a sintered structure have been obtained. The morphology of the obtained nanoalloys depends not only on the laser wavelength but also on the concentration of nanoparticles in the initial mixture. When the total concentration of Ag and Au nanoparticles in the mixture is increased, large-scale interlinked networks have been observed upon laser irradiation. It is expected that this selective heating strategy can be extended to prepare other bi- or multi-metallic nanoalloys.

Alloys↗

New insights into the biology of preeclampsia.

Despite recent research progress, the biology of preeclampsia is still poorly understood and neither effective prediction nor causal therapy have yet emerged. Nevertheless, recent studies have documented new and exciting pathophysiological mechanisms for the origin and development of preeclampsia. These studies provide a more differentiated view on alterations of particular peptide systems with strong impact on angiogenesis and cardiovascular regulation in this pregnancy disorder. With the identification of the antiangiogenic factor soluble fms-like tyrosine kinase 1 and the agonistic autoantibody to the angiotensin II type 1 receptor, two factors have been described with a clear linkage to the development of the disease. This review focuses on the most recent and relevant insights into the biology of preeclampsia and develops hypotheses regarding possible links between the reported aspects of preeclampsia.

Angiogenesis Modulating Agents↗

[Off-pump coronary artery bypass grafting. State of the art 2006 and results in comparison with conventional coronary artery bypass strategies].

Adverse clinical consequences associated with conventional coronary artery bypass surgery (CCAB) have largely been attributed to cardiopulmonary bypass circuit (CPB), hypothermic cardiac arrest, aortic cannulation, and cross-clamping. Consequently, there has been a growing interest in safer alternatives to CCAB including off-pump beating-heart bypass surgery (OPCAB). Initial concerns regarding completeness of revascularization at the lateral wall were addressed by using modern stabilizers and heart positioning devices. First studies tended to be nonrandomized clinical reports rather than controlled clinical trials with the potential risk of unbalanced baseline characteristics leading to biases in favor of OPCAB. Since these early reports, several randomized trials including mixed-risk patient populations have been completed. Most of them failed to reveal superiority of OPCAB concerning mortality and major perioperative morbidity due to statistically underpowered design to detect clinically important but infrequent adverse outcome events. Likewise, in most of the recently published meta-analyses of randomized trials no difference in early mortality, myocardial infarction or stroke rate was found, but OPCAB was superior regarding blood loss, transfusion requirement, rethoracotomy, ventilation time, ICU (intensive care unit) and hospital stay and resource utilization as illustrated in Table 1. Most of the large observational studies comparing OPCAB and CCAB strategies demonstrated a benefit of OPCAB concerning early mortality, myocardial infarction and stroke rate as summarized in Table 2. However, in few published follow-up studies no significant differences concerning recurrence of angina, reintervention rate und late mortality were found. The decision between OPCAB and CCAB has to weigh several factors, including the likely risks and benefits of the two approaches for the particular patient, the experience of the surgeon, the complexity of the coronary disease, and the required coronary revascularization.

Coronary Artery Bypass↗

Autonomic cardiovascular control in pregnancies with abnormal uterine perfusion.

BACKGROUND: Abnormal uterine perfusion is associated with the development of hypertensive pregnancy disorders. However, its impact on maternal autonomic cardiovascular control is poorly understood. The aim of our study was to investigate the adaptation of autonomic control during pregnancy with abnormal uterine perfusion with normal and pathologic outcome in comparison to normal pregnancies. based on blood pressure variability (BPV), baroreflex sensitivity (BRS), and heart rate variability (HRV) analyses. METHODS: A total of 32 healthy pregnant women (CON, age 28 years, range 24 to 31 years); 16 women with abnormal uterine perfusion and normal outcome (AP-NO, age 29 years, range 28 to 33 years); and 19 women with abnormal uterine perfusion and pathologic outcome (AP-PO, age 26 years, range 25 to 30 years), were recruited for this longitudinal study. Beginning in the 20th week of pregnancy, the women were monitored every fourth week until delivery. For the analysis of BPV, BRS, and HRV, high-resolution ECG, and noninvasive continuous blood pressure (BP) recordings were taken simultaneously for 30 minutes. RESULTS: CON showed pregnancy-induced adaptation of cardiovascular control; in the course of gestation BPV was increased while parameters of HRV and BRS were reduced. On the contrary, no changes during the second half of pregnancy could be observed in pregnancies with abnormal perfusion. Variability parameters were significantly altered in women with abnormal perfusion compared with CON, whereas these changes were more pronounced in AP-PO compared with AP-NO. CONCLUSIONS: Abnormal uterine perfusion, independently of the pregnancy outcome, has a significant impact on maternal cardiovascular control. Measures of BPV, BRS and HRV might be used for improved risk stratification.

Adult↗

Transapical aortic valve implantation: an animal feasibility study.

BACKGROUND: Percutaneous aortic valve implantation has recently been performed in nonsurgical patients with severe aortic stenosis. Retrograde valve delivery has been problematic because of the size of the delivery system and concomitant peripheral vascular disease. We investigated a minimally invasive approach through the left ventricular apex for antegrade placement of a device-deliverable valve. METHODS: Transapical aortic valve implantation was performed using a 23-mm equine valve mounted on a stainless steel stent in 24 swine (weight range, 35 to 45 kg). A limited or full sternotomy approach was used to access the apex of the heart. The crimped valve was introduced through a sheath in the left ventricular apex. Fluoroscopy and echocardiography were used for guidance. Deployments were performed on the beating heart either with ventricular unloading using femoral extracorporeal circulation or rapid ventricular pacing. RESULTS: All valves were successfully delivered at the selected target site with acceptable visualization of the noncalcified aortic annulus. Valve migration occurred during eight deployments (two distal and six retrograde) secondary to persistent cardiac output, unfavorable annular anatomy, and dislodgement by the delivery catheter. Exact positioning of the nonmigrated valves at the aortic annulus was examined by necropsy of all animals at the end of the procedures. Paravalvular leak was noted in 14 of 18 (77.8%) valves remaining in situ. CONCLUSIONS: The transapical approach was used for the successful antegrade placement of a stented valve, obviating the technical problems associated with a large delivery system transiting the peripheral vascular system. Stent design contributing to paravalvular leak remains problematic.

Animals↗