Prospectively randomized evaluation of stented versus stentless aortic valve bioprostheses.
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Aged↗
Biomedical subjects
Thomas Walther
Publications and source records attributed to Thomas Walther.
Structure and regulation of the murine Mash2 gene.
Transcription factors of the basic helix-loop-helix family such as Mash2 are essential for adequate differentiation of the trophoblast. Disruption of the Mash2 gene leads to early intrauterine death caused by placental insufficiency with an absent spongiotrophoblast and an underdeveloped chorion. The aim of the present study was to analyze the structure of the murine Mash2 gene, to screen a broad spectrum of organs for its expression, and to investigate placental Mash2 expression at different gestational ages. The RNase protection assay identified, in addition to the postulated Mash2 mRNA, two unexpected Mash2 transcripts that could be confirmed by a 5' rapid amplification of cDNA ends. However, all three transcripts were detectable exclusively in murine placenta and not in other organs, such as the ovary, uterus, skin, lung, femur, skeletal muscle, kidney, skull, adrenal gland, tongue, stomach, spleen, skin, testis, or pancreas. Sequence analysis disclosed an additional transcription start site upstream of exon 2. Placental Mash2 mRNA is measurable at all investigated stages of gestation. After its initial detection on Day 8.5 postcoitum (p.c.; set to 100%; 100.0% +/- 28.4%), the Mash2 mRNA concentration increases significantly and reaches a maximum of 812.0% +/- 69.7% on Day 12.5 p.c. The second half of gestation is marked by a more than 8-fold Mash2 decrease by Day 18.5 p.c. (77.0% +/- 28.4%). A 36.9% +/- 4.7% level of placental Mash2 mRNA is measurable at term.
Animals↗
Differential regulation of in vivo angiogenesis by angiotensin II receptors.
Angiotensin II (ANG II), a key regulator of blood pressure and body fluid homeostasis, exerts mitogenic effects on endothelial cells. We therefore hypothesized that ANG II could be a mediator between homeostatic changes within the vascular perfusion bed and growth factor-driven angiogenesis. In the present study, we applied the alginate implant angiogenesis model in mice with normal ANG II levels, elevated ANG II levels by transgenic overexpression of angiotensinogen (AOGEN), or in AT2 receptor-deficient mice. We demonstrate that a decrease in the amount of circulating ANG II by the angiotensin-converting enzyme (ACE) inhibitor enalapril or the AT1 receptor antagonist losartan induced a stimulation of in vivo angiogenesis implying an inhibitory function of ANG II through the AT1 receptor. However, the strong increase of angiogenesis in AOGEN-transgenic mice compared with mice with normal ANG II levels suggests additional stimulatory activity. We showed that the ANG II-induced stimulation of angiogenesis is linked to the AT2 receptor as an impaired induction of angiogenesis was obtained in AT2 receptor knockout mice. These findings provide the first evidence that the AT2 receptor mediates a stimulation of in vivo angiogenesis and indicate that ANG II is a humoral regulator of peripheral angiogenesis involving two receptor subtypes with opposing actions.
Alginates↗
Computer-enhanced endoscopic coronary artery bypass grafting: the da Vinci experience.
Anatomical and technical limitations as well as human factors render endoscopic coronary artery bypass surgery difficult. The da Vinci telemanipulator overcomes some of these shortcomings by restoring the dexterity and precision of a distant operator within the confined space in a closed-chest environment. Using the da Vinci system, total endoscopic coronary artery bypass grafting has evolved from a merely experimental surgical approach to a clinically applicable treatment option. Initially exclusively performed on the arrested heart, adjunct technologies such as endoscopic vacuum-assisted stabilizers now allow a single-vessel closed-chest beating heart procedure in selected patients. Despite the technical progress, endoscopic multivessel bypass grafting has yet to be achieved. The development of endoscopically applicable anastomotic devices and heart-positioning devices along with further refinements in telemanipulator technology, better optical systems, and image guided augmented reality scenarios may facilitate endoscopic bypass grafting in the future.
Cardiac Surgical Procedures↗
Left ventricular reverse remodeling after surgical therapy for aortic stenosis: correlation to Renin-Angiotensin system gene expression.
BACKGROUND: Surgical therapy for aortic stenosis leads to reverse remodeling, with normalization of left ventricular hypertrophy (LVH). The aim of this study was to examine Renin-Angiotensin system (RAS) gene expression in this setting. METHODS: Growing sheep (n=44) underwent supracoronary aortic banding for controlled induction of LVH at the age of 6 to 8 months (A=baseline). Surgical revision to completely release the pressure gradient was performed 8.3+/-1 months later (B). The animals were sacrificed after another 10.1+/-2 months (C). Along with hemodynamic measurements, subtractive hybridization and competitive polymerase chain reaction were applied to quantify mRNA expression for angiotensin-converting enzyme (ACE) and angiotensin receptors 1 and 2 (AT1-R and AT2-R). RESULTS: Left ventricular mass index was 82+/-21 g (A), 150+/-33 g (B), and 78+/-18 g (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter was 11.3+/-0.8 (A), 15.9+/-1.2 (B), and 11.4+/-1 (C) microm, P<0.01. Gene expression was as follows: ACE 0.8+/-0.05 (A), 1.3+/-0.08 (B), and 0.9+/-0.06 (C), P<0.01; AT1-R 0.7+/-0.06 (A), 0.9+/-0.07 (B), and 0.3+/-0.04 (C), P<0.01; AT2-R 0.5+/-0.05 (A), 0.2+/-0.04 (B), and 0.5+/-0.05 (C), P<0.01. CONCLUSION: LVH in aortic stenosis coincides with significant alterations of the RAS. Surgical therapy leads to reverse remodeling, which is paralleled by regression of RAS gene expression.
Animals↗
High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study.
BACKGROUND: Administration of 13-cis retinoic acid (isotretinoin) for acne is occasionally accompanied by hyperlipidemia. It is not known why some persons develop this side effect. OBJECTIVE: To determine whether isotretinoin triggers a familial susceptibility to hyperlipidemia and the metabolic syndrome. DESIGN: Cross-sectional comparison. SETTING: University hospital in Lausanne, Switzerland. PARTICIPANTS: 102 persons in whom triglyceride levels increased at least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated. MEASUREMENTS: Waist-to-hip ratio; fasting glucose, insulin, and lipid levels; and apoE genotype. RESULTS: Hyperresponders and nonresponders had similar pretreatment body weight and plasma lipid levels. When reevaluated approximately 4 years after completion of isotretinoin therapy, hyperresponders were more likely to have hypertriglyceridemia (triglyceride level > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% CI, 1.6 to 13.8]), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI, 1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to 59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to 5.7]). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 1.5 to 8.0]). Lipid response to isotretinoin was closely associated with the apoE gene. CONCLUSION: Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.
Acne Vulgaris↗
Reduced hypertension-induced end-organ damage in mice lacking cardiac and renal angiotensinogen synthesis.
Hypertension-induced damage of kidney and heart is of major clinical relevance, but its pathophysiology is only partially understood. As there is considerable evidence for involvement of angiotensin II, we generated a new mouse model by breeding angiotensinogen (AOGEN) deficient mice with transgenic animals expressing the rat AOGEN gene only in brain and liver. This genetic manipulation overcame the hypotension of AOGEN-deficient mice and even caused hypertension indistinguishable in its extent from the parent transgenic mice with an intact endogenous AOGEN gene. In contrast to normal mice, however, crossbred animals lacked detectable expression of AOGEN in kidney and heart. As a consequence they showed markedly reduced cardiac hypertrophy and fibrosis. Furthermore, hypertension-induced alterations in kidney histology and function were less pronounced in crossbred mice than in equally hypertensive animals expressing AOGEN locally. The dysmorphogenesis observed in kidneys from AOGEN-deficient mice was absent in mice expressing this gene only in liver and brain. Our results support an important role of local AOGEN expression in hypertension-induced end-organ damage but not in the development of the kidney.
Angiotensinogen↗
Imprinting of the murine MAS protooncogene is restricted to its antisense RNA.
The Mas protooncogene encodes a G protein-coupled receptor with the common seven transmembrane domains and may be involved in the actions of angiotensins. The gene is located in close proximity to the paternally imprinted Igf2r gene and its maternal imprinting has been reported but remained controversial. We used mice carrying a targeted deletion of the Mas protooncogene on the maternal or paternal chromosome to clarify this issue. In all Mas-expressing organs of adult mice such as heart, kidney, testis or brain, no Mas mRNA was missing in heterozygous animals inheriting the deleted allele from the father excluding mono-allelic paternal expression. However, we show exclusive paternal expression of a Mas antisense RNA, confirming the maternal imprinting of this antisense RNA in all investigated adult tissues and in embryos. Our results strongly suggest that Mas is not imprinted in mice but that an antisense RNA probably starting in the neighboring Igf2r gene is maternally imprinted in both embryos and adult organs.
Animals↗
Fetal, neonatal cord, and maternal plasma concentrations of angiotensin-converting enzyme (ACE).
OBJECTIVES: Angiotensin converting enzyme (ACE), a component of the renin-angiotensin system (RAS), catalyses the degradation of angiotensin I to angiotensin II. It was the aim of the present study to measure ACE activity in human fetal blood and to determine its changes with advancing gestational age. METHODS: Fetal blood was sampled by cordocentesis from six control fetuses and six fetuses with Rh isoimmunisation. Cord blood was sampled from six preterm neonates, 15 neonates after spontaneous delivery at term and six neonates at term after caesarean section. In addition, maternal ACE values were determined. ACE activity was measured using the miniaturised fluorimetric method. RESULTS: In normal fetuses (13.31+/-1.41 nmol HL/min/ml) and fetuses with Rh isoimmunisation (13.08+/-2.00 nmol HL/min/ml, p<0.05). Neonatal cord blood of preterm newborns (10.43+/-0.69 nmol HL/min/ml) and term newborns (8.99+/-0.49 nmol HL/min/ml) showed a significantly decreased ACE activity compared to the fetal controls. CONCLUSION: We conclude that the high fetal ACE activity and the stringent regulation with advancing gestational age indicate the physiological importance of the enzyme during prenatal development.
Female↗
[Arterial revascularization of coronary vessels].
UNLABELLED: ARTERIAL GRAFTS: Atherosclerosis is the major cause of late vein graft failure and has led to the use of arterial grafts. The use of the left internal thoracic artery (ITA) is associated with improved survival which has been proven in numerous studies. Recent studies have also demonstrated a survival benefit of double over single ITA graft use. Especially in younger patients bilateral ITA grafting is recommended. SURGICAL TECHNIQUE: In terms of dissection of the graft, the technique of skeletizing the artery seems beneficial especially in diabetics to decrease the likelihood of mediastinitis. The radial artery is mainly used as a T graft in order to achieve complete arterial revascularization. RESULTS: While patency rates seem superior as compared to vein grafts, a survival benefit has yet to be proven. Irrespective of graft type, in-situ-grafts have a superior patency as opposed to free grafts. As has long been demonstrated with vein grafts, patency of arterial grafts also depends on the size of the recipient vessel. Grafts to the distal circumflex and distal right coronary artery have worse patency rates than grafts to the LAD. Conflicting results exist concerning the gastroepiploic artery; its use can only be recommended if the vessel is of good caliber. All other arterial conduits are used infrequently and there are no data to draw any meaningful conclusion for routine use. Arterial revascularization on the beating heart is feasible and short and midterm follow-up data are encouraging. CONCLUSION: Our current policy is to perform complete arterial revascularization in all patients under the age of 70 using bilateral ITAs and radial arteries.
Arteries↗
Endoscopic internal thoracic artery dissection leads to significant reduction of pain after minimally invasive direct coronary artery bypass graft surgery.
BACKGROUND: The aim of this study was to evaluate postoperative pain levels after endoscopic versus conventional internal thoracic artery (ITA) dissection for minimally invasive direct coronary artery bypass graft surgery (MIDCABG) surgery. Results were compared with pain levels associated with conventional cardiac bypass operations through a median sternotomy. METHODS: Of 190 patients included in this prospective study, 24 patients had endoscopic ITA takedown (MIDCABG-endo) using the da Vinci telemanipulator followed by a manual coronary anastomosis through a left minithoracotomy. A conventional MIDCABG operation (MIDCABG-conv) was performed in 73 patients with ITA preparation under direct vision. Postoperative pain levels after conventional CABG through a median sternotomy (CABG-conv, n = 93) served as controls. A standarized questionnaire including visual analog scale (VAS) was used for prospective pain assessment from POD 1 to 7. RESULTS: Pain levels (VAS) declined in all groups from POD 1 to 7. Overall pain levels were significantly lower in the MIDCABG-endo group as compared with MIDCABG-conv and CABG-conv groups, respectively (p < 0.001, general linear model). There was no significant difference between the MIDCABG-conv and CABG-conv (p = not significant, general linear model) groups. Furthermore, patients after MIDCABG-endo required fewer nonsteroidal anti-inflammatory drugs and opioid medications, postoperatively. CONCLUSIONS: An endoscopic ITA takedown in MIDCABG surgery leads to significantly reduced postoperative pain levels possibly because of less rib retraction.
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Minimal access aortic valve replacement: effects on morbidity and resource utilization.
BACKGROUND: The aim of this study was to compare outcomes in patients undergoing minimal access versus conventional aortic valve replacement (AVR). METHODS: We reviewed prospectively gathered data on all patients who were undergoing first-time AVR, with or without replacement of the ascending aorta, over a 1-year period at our institution. RESULTS: A total of 176 patients underwent minimal access and 258 underwent conventional AVR. The conventional group was older, had more incidence of diabetes, and more aortic stenosis (all p < 0.05). Eight minimal access AVR patients (2%) required conversion to a complete sternotomy. Minimal access AVR patients had longer aortic crossclamp times than conventional AVR patients (60 +/- 22 vs 55 +/- 23 minutes, p = 0.03) but similar CPB times (93 +/- 38 vs 88 +/- 42 minutes, p = 0.20). Postoperative creatine kinase-MB levels were similar for the two groups. Total postoperative blood loss was significantly lower in the minimal access group, and these patients received less red blood cell and fresh frozen plasma transfusions. Minimal access AVR patients were less likely to have postoperative respiratory failure (3% vs 10%); they had shorter intensive care unit stays (3.7 +/- 5.4 vs 4.5 +/- 5.6 days) and shorter hospital stays (10 +/- 6 vs 12 +/- 7 days, all p < 0.05). Mortality was lower in patients undergoing minimal access surgery (3% vs 9%, p = 0.008) by univariate analysis. Multivariate predictors of mortality were age, hypertension, and CPB time. CONCLUSIONS: Although patient selection may have influenced some of the observed differences between our patient groups, minimal access surgery appears to be associated with decreased morbidity and resource use when compared to conventional AVR.
Aortic Valve↗
Regulation of cardiac bradykinin B1- and B2-receptor mRNA in experimental ischemic, diabetic, and pressure-overload-induced cardiomyopathy.
Although kinins have been associated with the regulation of cardiovascular function in left ventricular hypertrophy (LVH) as a consequence of hypertension, myocardial infarction (MI), and/or diabetic cardiomyopathy, less is known about their receptor regulation under these conditions. We have therefore investigated the bradykinin B1-receptor (B1R) and B2-receptor (B2R) mRNA expression in rat models of MI, LVH and diabetes mellitus (DM). Sprague-Dawley rats (SD) were submitted to permanent ligation of the left descending coronary artery (LAD) to induce a MI, whereas DM was induced by a single injection of streptozotocin (STZ). LVH was induced after thoracic aortic banding (AB). Three weeks after MI, six weeks after STZ injection or six weeks after AB, left ventricular (LV) function was characterized using a Millar-tip catheter. Cardiac B1R- and B2R-mRNA expression were analyzed by specific RNase-protection assays (RPA). LV contractility (dP/dt max) was impaired by 40-48% in rats after induction of MI or DM compared to their controls. However, despite an enormous increase in LV end-diastolic pressure (LEVDP) to 310% after AB, LV contractility did not differ compared to the controls. These hemodynamic changes were accompanied by an up-regulation of cardiac B1R- (MI, 288%; STZ, 215%; AB, 4180%) and B2R-mRNA expression (MI, 122%; STZ, 288%; AB, 96%). Up-regulation of both BK-receptor (BKR) types in early stages of cardiac wound healing induced by ischemia and in chronic stages of cardiac remodeling induced by pressure-overload or by hyperglycemia indicates that kinins play a major role in the complex processes of cardiac tissue injury and repair.
Animals↗
Experimental evaluation and early clinical results of a new low-profile bileaflet aortic valve.
We performed an experimental and clinical evaluation of a new low-profile bileaflet aortic valve (Regent, St. Jude Medical Inc., St. Paul, MN, U.S.A.). Common valve sizes were experimentally tested for leakage volume, pressure drop, and transvalvular hemodynamics using a pulse duplicator. Thirty patients (mean age 60 +/- 7 years, predominant valve stenosis n = 25) received the Regent prosthesis for initial clinical evaluation. In vitro evaluation revealed equivalent leakage volumes, larger performance indices (0.552 versus 0.513), and lower pressure drops in comparison to SJM hemodynamic plus valve controls. Clinically, 21 mm (n = 9), 23 mm (n = 12), and 25 mm (n = 9) valves were implanted with no significant perioperative complications. Echocardiography revealed low transvalvular flow velocities (2.2 +/- 0.4 m/s) and low pressure gradients (20 +/- 6 mm Hg) postoperatively and at 6 months follow-up. In vitro testing and early clinical results are promising; however, long-term performance has to be proven.
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Hemodynamic evaluation of stentless mitral valve replacement.
The purpose of this study was to evaluate the perioperative and postoperative hemodynamic function of recently introduced stentless mitral valves (SMVs). Forty-two selected patients who had received the SMV since 1997 had preoperative, postoperative, and follow-up transthoracic echocardiographic (TTE) examinations. Transesophageal echocardiography (TEE) was applied routinely during the operation as well as postoperatively if indicated. Adequate SMV function was seen in all patients perioperatively. Echocardiographic prediction of valve size and of papillary muscle distances was correct in 37 of 42 patients. Transvalvular blood flow velocities were 1.6 +/- 0.2 m/s postoperatively versus 1.8 +/- 0.3 m/s at 1 year and 1.7 +/- 0.3 m/s at 3-year follow-up. Mean transvalvular gradients were 4.3 +/- 1.6, 3.8 +/- 1.9, and 4.7 +/- 1.1 mm Hg, respectively. TEE and TTE are extremely useful to assist SMV implantation as well as for regular follow-up evaluation. The hemodynamic function after SMV implantation with preservation of the annulo-ventricular continuity is promising.
Aged↗
Ischemic injury in experimental stroke depends on angiotensin II.
Since pharmacological interactions of the renin-angiotensin system appear to alter the neurological outcome of stroke patients significantly, we examined the effect of elevated levels of angiotensin II and the role of its receptor subtype AT1 in brain infarction in transgenic mice after focal cerebral ischemia. Angiotensinogen-overexpressing and angiotensin receptor AT1 knockout mice underwent 1 h or 24 h permanent middle cerebral artery occlusion (MCAO). The current study revealed a much smaller penumbra size, i.e., brain tissue at risk, in angiotensinogen-overexpressing animals compared with their wild-type subgroup after 1 h MCAO, but an enlarged infarct size after 24 h. In contrast, a smaller lesion area of energy failure and a much larger penumbral area were found in AT1 knockout mice compared with wild-type littermates. Lower perfusion thresholds for ATP depletion and protein synthesis inhibition after MCAO in AT1-deficient mice and reduced cell damage in an in vitro model using embryonic neurons of AT1 knockout mice suggest injury mechanisms independent of arterial blood pressure. Our data, therefore, demonstrate a direct correlation between brain angiotensin II and the severity of ischemic injury in experimental stroke.
Angiotensin II↗
AT1 receptor blockade increases cardiac bradykinin via neutral endopeptidase after induction of myocardial infarction in rats.
ACE inhibition protects the heart against ischemic injury by reducing angiotensin II and promoting bradykinin (BK) accumulation. Since neutral endopeptidase (NEP) metabolizes BK, we determined its activity after induction of myocardial infarction (MI) and examined whether it is influenced by treatment with an ACE inhibitor or AT1 receptor blocker. Rats were studied 6 days and 3 wk after coronary occlusion. Starting 48 h after MI induction, additional animals were treated with the ACE inhibitor quinapril (2 mg x kg(-1) x day-1) or the AT1 blocker irbesartan (50 mg x kg(-1) x day-1). Animals were hemodynamically characterized. Finally, NEP-specific activity and BK concentrations were detected in homogenates of heart compartments. Quinapril and irbesartan treatment improved left ventricular function 6 days and 3 wk after MI induction, and NEP activity was elevated only in the infarcted area of untreated compared with sham-operated rats. After 6 days, irbesartan reversed this increase by 80% and quinapril by 35%. Quinapril had no effect after 3 wk, whereas irbesartan almost completely blocked the increased NEP activity in the infarcted area and concomitantly induced a further rise in the BK concentrations. These results indicate mechanisms of NEP regulation influenced by the AT1 receptor. Our data suggest that NEP is more decisive than ACE in mediating BK degradation and may indicate BK involvement in the cardioprotective effects of AT1 antagonists.
Angiotensin Receptor Antagonists↗
Natriuretic peptide system in fetal heart and circulation.
Atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide belong to a family of hormones that have diuretic, natriuretic and vasodepressor activity and play a part in pressure and volume homeostasis in adults. As little is known about the natriuretic peptides during cardiac maturation, this review summarizes current knowledge about the early expression of components of the natriuretic peptide system in the heart during embryonic and fetal development. The data indicate a functional importance of the fetal natriuretic peptide system, especially under pathophysiological conditions. Thus, in the fetus, the system fulfils important beneficial compensatory roles in cardiovascular disease, rather than in day-to-day pressure and volume homeostasis. In comparison with data on the relevance of natriuretic peptides in adults, those summarized here indicate a functional maturation of the natriuretic peptide system during ontogeny in mammals.
Animals↗