AIM:To describe the long-term experience of a simplified frozen elephant trunk technique (sFETT) used in complicated acute type A aortic dissection (AAAD) treatment.METHODS AND RESULTS:Between January 2001 and December 2012, 34 patients (mean age 59.9 ± 11.0 years) with complicated AAAD (DeBakey I) underwent an emergency surgery including sFETT. sFETT consisted in gluing the dissected aortic arch wall layers with gelatine-resorcinol adhesive and video-assisted antegrade open arch aortic stent-graft deployment in the arch or proximal descending aorta. In addition to sFETT, the aortic root was addressed with standard techniques. A 30-day mortality was 14.7% (five patients) due to bleeding (1), multiple organ failure (2), and colon ischemia (2). Postoperative morbidity included neurological (2), renal (1) and cardio-pulmonary complications (4), as well as wound infection (1). Mean follow-up was 74.4 ± 45.0 months. Actual survival rates were 73.5% at 1 year, 70.2% at 5 years, and 58.5% at 13 years of follow-up. Six patients died during long-term follow-up from heart failure (1) and unknown reasons (5). Five patients required reoperation for aortic arch (3) or aorto-iliac (2) progression of aneurysm during the mid- and long-term follow-up. The remaining patients showed favorable evolution of the dissected aorta with false lumen occlusion in most cases and stable aortic diameters.CONCLUSIONS:In AAAD patients, sFETT as used in our series is an easy and safe technique to repair the aortic arch. Long-term results after sFETT showed false lumen occlusion and stable aortic diameter in up to 13 years of follow-up.

Objective: Local changes in wall shear stress (WSS) contribute to vascular wall thickening and subsequent stenosis. Restenosis after stenting is a major concern, especially in the superficial femoral artery (SFA) of patients with peripheral arterial disease (PAD). Local alterations in WSS after stenting might contribute to restenosis/reocclusion. To test the hypothesis that WSS is impaired along the stented SFA segment, we studied the profile of WSS along the femoro-popliteal axis after stent placement in a cross-sectional design.Methods: Eighty-seven patients with PAD (89 limbs) were included one day after stenting of the SFA. Flow velocities (peak and mean) and vessel diameter were measured by duplex ultrasound in five predefined segments along the femoro-popliteal axis, at rest and after exercise (30 toe raises); WSS (peak and mean) was calculated from flow velocities, vessel diameter and whole blood viscosity.Results: WSS progressively declined along the stented segment at rest (peak WSS, p < 0.0001; mean WSS, p < 0.05); after exercise, WSS increased in all segments (all p < 0.001), but, again, progressively declined along the stent (peak WSS, p < 0.0001; mean WSS, p < 0.05). The internal vessel diameter remained unchanged after exercise in the stented and in the non-stented parts of the femoro-popliteal axis (all p > 0.05).Conclusion: In PAD patients with SFA stenting WSS is impaired along the femoro-popliteal axis. The consequences of this finding in terms of local effects on the vessel wall that might favor restenosis/reocclusion needs further investigation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis.

Objective Percutaneous closure of a patent foramen ovale (PFO) is a technically simple and safe procedure. PFO is a common finding present in up to one third of the population. Although several conditions such as stroke, migraine, and sleep apnoea have been associated with a PFO, as underlined by observational studies, no causal relationship has been documented so far. As this setting may potentially leave more space for the involved physicians for the choice of treatment, we hypothesized that social characteristics of the patient with a PFO might play a role.Methods We retrospectively analysed the data of 153 patients with a cerebrovascular and/or peripheral ischaemic event with the diagnosis of a PFO as documented in echocardiography from 2000 until 2005 at the University Hospital in Zurich, Switzerland.Results Forty-four patients (= 23%) underwent catheter-based PFO closure. There was no significant difference with respect to age (< 40 years: P=0.094, ns; 40-59 years: P=0.923, ns; > 60 years: P=0.234, ns), gender (P=0.356, ns) and insurance status (< 40 years: P = 0.15, ns; 40-59 years: P=0.37, ns; > 60 years: P=0.26, ns) between those who underwent percutaneous PFO closure and those who did not.Conclusion We conclude from this single-centre experience that social characteristics of patients only have a marginal impact on the indication of percutaneous closure of a PFO, if at all.

AIMS:Prostaglandin endoperoxide H(2) synthase (PGHS) is a well-known target for peroxynitrite-mediated nitration. In several experimental macrophage models, however, the relatively late onset of nitration failed to coincide with the early peak of endogenous peroxynitrite formation. In the present work, we aimed to identify an alternative, peroxynitrite-independent mechanism, responsible for the observed nitration and inactivation of PGHS-2 in an inflammatory cell model. RESULTS:In primary rat alveolar macrophages stimulated with lipopolysaccharide (LPS), PGHS-2 activity was suppressed after 12 h, although the prostaglandin endoperoxide H(2) synthase (PGHS-2) protein was still present. This coincided with a nitration of the enzyme. Coincubation with a nitric oxide synthase-2 (NOS-2) inhibitor preserved PGHS-2 nitration and at the same time restored thromboxane A(2) (TxA(2)) synthesis in the cells. Formation of reactive oxygen species (ROS) was maximal at 4 h and then returned to baseline levels. Nitrite (NO(2)(-)) production occurred later than ROS generation. This rendered generation of peroxynitrite and the nitration of PGHS-2 unlikely. We found that the nitrating agent was formed from NO(2)(-), independent from superoxide ((•)O(2)(-)). Purified PGHS-2 treated with NO(2)(-) was selectively nitrated on the active site Tyr(371), as identified by mass spectrometry (MS). Exposure to peroxynitrite resulted in the nitration not only of Tyr(371), but also of other tyrosines (Tyr). INNOVATION AND CONCLUSION:The data presented here point to an autocatalytic nitration of PGHS-2 by NO(2)(-), catalyzed by the enzyme's endogenous peroxidase activity and indicate a potential involvement of this mechanism in the termination of prostanoid formation under inflammatory conditions.

BACKGROUNDStatins are used for the treatment of hypercholesterolemia. Although they are well known to have pleiotropic effects, their dose-dependent influence on platelet aggregation, hemorheologic properties and the plasma levels of homocysteine in patients with peripheral arterial disease (PAD) has not been thoroughly investigated so far.METHODS AND RESULTSFrom a total of 100 patients with PAD 48 patients were randomized to a treatment with atorvastatin 80 mg/d for six months, and 52 patients served as controls who continued their medication including statins in lower doses. At baseline and at six months' follow up we assessed platelet aggregation upon stimulation with ADP, collagen and epinephrine using light transmission aggregometry. Furthermore, we determined major hemorheologic variables as well as the plasma levels of homocysteine, folic acid, and vitamin B6 and B12. No patient had obtained folic acid or B vitamin supplement. Platelet aggregation upon agonist-induced stimulation did not differ between patients under high-dose atorvastatin therapy and controls at baseline and after six months (p > 0.05). All hemorheologic parameters (plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, platelets, leucocytes) measured at baseline and after six months were not significantly different between both groups, too. After therapy with 80 mg atorvastatin homocysteine levels were significantly elevated as compared with baseline values (p = 0.0007), whereas levels remained unchanged in the control group. Folic acid levels were higher in the patients receiving high-dose atorvastatin as compared with controls both at baseline (p = 0.002) and at six months' follow up (p = 0.034). No significant difference in vitamin B6 and B12 levels both at baseline and after six months could be detected in either group.CONCLUSIONSTreatment with 80 mg atorvastatin did not affect platelet aggregation and major hemorheologic parameters. The finding of an increase of homocysteine plasma levels in the presence of rather elevated levels of folic acid needs further investigation.

AIMSCardiac output (CO) measurements from three-dimensional (3D) trans-mitral Doppler echocardiography are prone to error as manual selection of the region of interest (i.e. the site of measurement) is required. We newly developed an automated, user-independent algorithm to select the site of colour Doppler CO measurement. We aimed to validate this new method by benchmarking it against thermodilution, the current gold standard for CO measurements.METHODS AND RESULTSTransoesophageal colour 3D Doppler echocardiographic studies were obtained from 15 patients who also had received a pulmonary catheter for invasive CO measurements. Trans-mitral flow was determined using a novel operator-independent algorithm to automatically select the optimal site of measurement. The operator-independent CO measurements were referenced against thermodilution. A good correlation was found between operator-independent Doppler flow computations and thermodilution with a mean bias of 0.09 L/min, standard deviation of bias 1.3 L/min, and a 26% error (2 SD/mean CO). Mean CO was 4.94 L/min (range 3.10-7.10 L/min).CONCLUSIONOur findings demonstrate that CO computation from transoesophageal colour 3D Doppler echo can be automated concerning the site of velocity measurement. Our operator-independent algorithm provides an objective and reproducible alternative to thermodilution.

Aging is an important risk factor for the development of cardiovascular diseases, which can be accelerated by atherosclerosis, diabetes, hypercholesterolemia, or obesity. Vascular aging is mainly characterized by endothelial dysfunction, an alteration of endothelium-dependent signaling processes, and vascular remodeling. The underlying mechanisms include increased production of reactive oxygen species (ROS), inactivation of nitric oxide (center dot NO), and subsequent formation of reactive nitrogen and oxygen species (RNOS). Elevated RNOS may exhibit new messenger functions by posttranslational oxidative modification of intracellular regulatory proteins or lead to irreversible alterations of biological macromolecules. Various cellular sources may contribute to radical formation and are discussed in the context of the free radical hypothesis of aging. Clinically, endothelial dysfunction can he assessed by plethysmography, which may serve as an independent predictor for the risk of cardiovascular events. Current concepts in vascular aging, consequences for the development of cardiovascular events, and the particular role mitochondria may play in the development of RNOS-induced pathologic processes are discussed.

A middle-aged patient underwent computed tomographic (CT) coronary angiography as part of their investigative work-up for ischaemic heart disease. The patient had previously undergone percutaneous closure for an atrial septal defect and is still being followed up at their local hospital. Echocardiograms have been satisfactory. There were no other significant comorbidities. The clinical symptoms were of chest …

BACKGROUND:The aim of this study was to identify the predisposing factors for pseudoaneurysm formation after aortic valve replacement without previous endocarditis. METHODS:Echocardiography was used to identify patients. Parameters with influence on the occurrence of pseudoaneurysms were analyzed, and the odds ratio for the influence of the type of valve was estimated. The chi2 goodness-of-fit test was used to analyze whether location or underlying etiology was associated with an accumulated occurrence of a pseudoaneurysm. Fisher's exact test was used to assess a possible relation between the occurrence of a pseudoaneurysm after composite graft implantation and etiology or location. RESULTS:Patients treated with composite grafts had a 27-fold increased risk for developing pseudoaneurysms (psiMH=27; 95% confidence interval, 1.61-454.19) in comparison with aortic valve replacement only. There was a significant difference for the probability of different etiologies to occur (P=.032), with Stanford type A aortic dissection and aortic regurgitation being the most often occurring pathologies. Significant associations between the use of a composite graft and both the underlying etiology (P=.002) and the location of the pseudoaneurysm (P=.04) was found. Furthermore, patients with composite grafts had larger diameters of the aortic root compared with patients with aortic valve replacement only (P=.03). Neither the diameter of the annulus of the aortic valve (95% confidence interval, 0.89-1.32; P=.41) nor the diameter of the ascending aorta (95% confidence interval, 0.27-1.97; P=.54) had any influence on pseudoaneurysm formation. CONCLUSIONS:The underlying disorder, determining the surgical procedure, influences the risk for the development of pseudoaneurysms in patients without previous endocarditis. The location of most pseudoaneurysms at the level of the aortic root may be a consequence of its larger diameter.

Ageing is an important risk factor for the development of cardiovascular diseases. Vascular ageing is mainly characterized by endothelial dysfunction, an alteration of endothelium-dependent signalling processes and vascular remodelling. The underlying mechanisms comprise increased production of reactive oxygen species (ROS), inactivation of nitric oxide (.NO) and subsequent formation of peroxynitrite (ONOO-). Elevated ONOO- may exhibit new messenger functions by post-translational oxidative modification of intracellular regulatory proteins. Mitochondria are a major source of age-associated superoxide formation, as electrons are misdirected from the respiratory chain. Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is an integral part of the nucleoids and may protect mitochondrial DNA from ROS. A model linking .NO, mitochondria, MnSOD and its acetylation/deacetylation by sirtuins (NAD(+)-dependent class III histone deacetylases) may be the basis for a potentially new powerful therapeutic intervention in the ageing process.

Background: Isolated congenital cleft of the posterior leaflet of the mitral valve is a rare cause of mitral regurgitation (MR). This study describes the clinical, echocardiographic, and intraoperative findings as well as treatment options.Methods: Adults with an isolated cleft of the posterior mitral valve leaflet diagnosed by transthoracic echocardiography were evaluated with respect to clinical, echocardiographic, preoperative and intraoperative findings, and different surgical strategies.Results: The prevalence of isolated cleft of the posterior mitral valve leaflet in all patients examined was 0.11% (n = 22 out of 19 320 evaluated echocardiograms); mate gender was predominant (73%). Dyspnea on exertion was present in almost all patients with at least moderate regurgitation. The predominant localization of the cleft was within segment P2 (59%), followed by a cleft between P1/P2 (18%). An isolated cleft in segment P3 or segment P1 occurred twice in each segment (n = 2; 9%) and between P2/P3 once (n = 1; 5%). Regurgitation was severe in 50% (n = 11), moderate in 9% (n = 2), mild in 27% (n = 6), and only trivial in 14% (n = 3) of the patients. Surgical treatment involved reconstruction with ring annuloplasty in 45% (n = 10) and replacement in 4.5% (n = 1). A total of 11 patients (50%) with mostly mild or trivial mitral regurgitation were treated medically only.Conclusion: Two-dimensional high-resolution cross-sectional echocardiography allows the distinct diagnosis of a clefted posterior leaflet, whereas clinical presentation, electrocardiogram, chest x-ray, and angiography are failing to identify the correct etiology of MR in patients with isolated posterior leaflet cleft mitral valve (IPLCMV). Patients with moderate to severe MR were treated surgically with excellent outcome.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death In young adults. On the basis of histopathologicat findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bortonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. Hypothesis: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC.Methods: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls.Results: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (P <0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC.Conclusions: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bortonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Summary Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flowmediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06–8.6) versus 5.0 (0.76 vs. 8.1) %, p=0.96, and 0.76 (0.66–0.82) versus 0.73 (0.63–0.81) mm, p=0.41, respectively, in the atorvastatin group, and 2.66 (-1.9 – 6.9) versus 3.65 (0.0–8.6)%, p=0.02, and 0.78 (0.71–0.90) versus 0.77 (0.70–0.90) mm, p=0.48,in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21–3.28) to 1.86 (1.38–2.29) mM (p<0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94–3.16) vs.2.33 (1.82–2.84) mM, p=0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p= 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT andABI were also similar in patients with and without high-dose atorvastatin at six months.

Aggregation of activated platelets is considerably mediated by the autocrine action of thromboxane A2 (TxA2) which is formed in a prostaglandin endoperoxide H2 synthase-1 (PGHS-1 or COX-1)-dependent manner. The activity of PGHS-1 can be stimulated by peroxides, an effect termed "peroxide tone", that renders PGHS-1 the key regulatory enzyme in the formation of TxA2. Activated platelets release nitric oxide (*NO) and superoxide (O*2) but their interactions with the prostanoid pathway have been controversially discussed in platelet physiology and pathophysiology. The current study demonstrates that endogenously formed peroxynitrite at nanomolar concentrations, originating from the interaction of *NO and *O2, potently activated PGHS-1, which parallels TxA2 formation and aggregation in human platelets. Inhibition of the endogenous formation of either *NO or O*2 resulted in a concentration-dependent decline of PGHS-1 activity, TxA2 release, and aggregation. The concept of peroxynitrite as modulator of TxA2 formation and aggregation explains the interaction of *NO and O*2 with the PGHS pathway and suggests a mechanism by which antioxidants can regulate PGHS-1-dependent platelet aggregation. This may provide a molecular explanation for the clinically observed hyperreactivity of platelets in high-risk patients and serve as a basis for novel therapeutic interventions.

Ein Schwerpunktheft über „Venöse Erkrankungen“ in der Zeitschrift Herz ist eine Premiere. Und gewiss, auf den ersten Blick erscheint es möglicherweise etwas überraschend, sich einem solchen Thema in einer Zeitschrift mit kardiologischem Schwerpunkt und entsprechender Leserschaft zu widmen. Im Alltag jedoch werden Kardiologen, sei es in der eigenen Praxis, in vernetzten klinischen Kompetenzzentren der kardiovaskulären Medizin mit entsprechend enger interdisziplinärer Zusammenarbeit mit Angiologen, Radiologen und Chirurgen oder auf internistischen Intensivstationen, sicher regelmäßig mit hier behandelten Fragestellungen und Problemen konfrontiert. Am offensichtlichsten ist der Zusammenhang natürlich für die venöse Thromboembolie, ist doch die akute Lungenembolie bei älteren hospitalisierten Patienten nach Myokardinfarkt und zerebrovaskulärem Insult die häufigste Erkrankung des Herz-Kreislauf-Systems und auch auf Notfallstationen eine wichtige Differentialdiagnose bei Patienten mit Atemnot und/oder Thoraxschmerzen [1]. Schließlich zeigen verschiedene Untersuchungen, dass auf internistischen Stationen die Thromboembolieprophylaxe – in Gegensatz etwa zu Chirurgen und Frauenärzten – zu wenig eingesetzt wird [2]. Dies weist darauf hin, dass sich in den Fächern der Inneren Medizin nicht in gleicher Weise das Bewusstsein für eine angemessene Thromboembolieprophylaxe entwickelt hat wie in den chirurgischen Fächern, in welchen diese Komplikation nach ope-rativen Eingriffen sehr gefürchtet ist. Umso wichtiger erscheint es, den Schwerpunkt der Zeitschrift Herz diesem Themenbereich zu widmen. Und in der Tat zeigte eine kürzliche Untersuchung mit einem computerisierten Warnsystem für behandelnde Ärzte, dass damit nicht nur die Thromboembolieprophylaxe besser sichergestellt werden kann, sondern auch das Überleben der Patienten günstig beeinflusst wird [3]. Umso wichtiger ist eine gute Fortbildung in diesem Bereich. Das vorliegende Heft deckt folglich das für den klinischen Alltag relevante Spektrum venöser Erkrankungen ab und gibt einen hervorragenden Überblick über Physiologie, Pathophysiologie, Klinik, Diagnostik und Therapie von Venenleiden, wobei der Bogen von den potentiell akut lebensbedrohlichen Erkrankungen wie der Lungenembolie bis hin zu den vermeintlichen Schönheitsfehlern gespannt ist. Hauptfunktion der Venen des Herz-KreislaufSystems ist, wie im Artikel von S. Hochauf & Schellong, Dresden, über die Funktion des Venensystems dargelegt, zum einen die Speicherung des Blutvolumenanteils, welches aktuell nicht für die Zirkulation benötigt wird, zum anderen der Rücktransport des venösen Bluts zum Herzen [4]. Die Speicherfunktion, d.h. Erweiterung der Venen, wird durch elastische und kollagene Fasernetze in den verschiedenen Schichten der Venenwand gewährleistet. Entscheidende Mechanismen bei der Aufrechterhaltung eines regelrechten Blutrückflusses zum Herzen sind die Venenklappen als spezielle Strukturelemente der Intima sowie die thorakoabdominale Venenpumpe und die periphere Muskelpumpe der unteren Extremitäten. K. Böhler, Wien, Österreich, behandelt die (rhetorische) Frage, inwieweit die Varikose mehr als nur ein Schönheitsfehler ist [5]. Die Frage ist natürlich vor allem für die Behandlungsnotwendigkeit entscheidend. Während bei Patienten ohne signifikante Zeichen einer venösen Insuffizienz die individuellen Wünsche der Betroffenen noch im Vordergrund stehen, gerade auch bei zunehmender Anwendung neuerer, endoluminaler Therapieverfahren, welche im Beitrag besprochen werden, ist beim Auftreten venöser Ulzera die chirurgische Behandlung einschließlich autologer Spalthautdeckung ein Muss. Mit der Diagnostik venöser Erkrankungen beschäftigen sich D.D. Do & M. Husmann, Bern, Schweiz, in ihrem Beitrag [6]. Sowohl bei der Beurteilung des oberflächlichen wie auch des tiefen Venensystems hat sich in den letzten Jahren im klinischen Alltag immer mehr die nichtinvasive Duplexsonographie anstelle der Phlebographie, die gleichwohl für die Diagnostik tiefer Beinvenenthrombosen (TVTs) immer noch „Goldstandard“ bleibt, durchgesetzt. Weitere Vorteile der Duplexsonographie sind das Fehlen von Kontrastmittelund Strahlenbelastung. Die reine Diagnosestellung ist bei Varikose, Thrombophlebitis sowie der chronischen venösen Insuffizienz oft bereits klinisch gut möglich, die Duplexsonographie liefert zusätzlich exakte morphologische und auch funktionelle Informationen, z. B. zur weiteren Therapieplanung bei Varikose. Insbesondere in der Diagnostik der TVT ist die Duplexrespektive Kompressionssonographie mit einer Sensitivität von weit über 90% für die symptomatische proximale TVT und um 90% für die TVT am Unterschenkel zur Methode der ersten Wahl ge1 Klinik für Kardiologie, Departement Innere Medizin, HerzKreislaufZentrum, Universitätsspital Zürich, Schweiz.

Vascular aging is characterized by the presence of chronic oxidative stress. Although cytosolic Sod 1 has a key role in the detoxification of superoxide (·O2−), little is known about its importance in vascular aging. We found that inhibition of Sod 1 had no effect on ·O2− generation. Furthermore, its expression decreased in an age-dependent manner. Interestingly, Sod 1 loses its membrane-association and is also lost from the caveolae with increasing age. Instead, a relocation of Sod 1 to the mitochondria takes place, presumably in an attempt to maintain mitochondrial integrity and to counter-balance age-associated oxidative stress. Unlike Sod 2, which is constitutively expressed in mitochondria to control ·O2− radical fluxes, Sod 1 is not inactivated by peroxynitrite and is not nitrated as a function of age. These novel insights into oxidative stress-associated vascular aging and the understanding about how redox-systems are regulated in old age may identify new targets to ameliorate aging as the greatest cardiovascular risk factor.

Die kardiovaskuläre Medizin betreut ein breites Spektrum von Krankheitsbildern, Syndromen und Risikofaktoren[...]

We investigated the effects of aging and ischemia–reperfusion (I/R) injury on the expression and activity of nitric oxide ( • NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and old (31–34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for 30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R. However, SOD activity decreased from 7.55 ± 0.1 U/mg protein in young hearts to 5.94 ± 0.44 in old hearts ( P <0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 ± 0.41 U/mg protein; P <0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process.