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BACKGROUND: A detailed understanding of the sympathetic innervation of coronary arteries is relevant to facilitate the development of novel treatment approaches. AIMS: This study aimed to quantitatively examine periarterial innervation in human epicardial coronary arteries. METHODS: Coronary arteries with adjacent epicardial adipose tissue were excised along the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) from 28 body donors and examined histologically. Immunofluorescence staining was performed to characterise sympathetic nerve fibres. RESULTS: A total of 42,573 nerve fibres surrounding 100 coronary arteries (LMCA: n=21, LAD: n=27, LCx: n=26, RCA: n=26) were analysed. The nerve fibre diameter decreased along the vessel course (median [interquartile range]): (proximal 46 µm [31-73], middle 38 µm [26-58], distal 31 µm [22-46]; p<0.001), with the largest nerve fibre diameter along the LMCA (50 µm [31-81]), followed by the LAD (42 µm [27-72]; p<0.001). The total nerve fibre density was highest along the RCA (123 nerves/cm² [82-194]). Circumferentially, nerve density was higher in the myocardial tissue area of the coronary arteries (132 nerves/cm² [76-225]) than in the epicardial tissue area (101 nerves/cm² [61-173]; p<0.001). The median lumen-nerve distance was smallest around the LMCA (2.2 mm [1.2-4.1]), followed by the LAD (2.5 mm [1.1-4.5]; p=0.005). CONCLUSIONS: Human coronary arteries are highly innervated with sympathetic nerve fibres, with significant variation in the distribution and density. Understanding these patterns informs pathophysiological understanding and, potentially, the development of catheter-based approaches for cardiac autonomic modulation.
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Vasos Coronarios , Humanos , Vasos Coronarios/inervación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Sistema Nervioso Simpático , Tejido Adiposo/inervación , Pericardio/inervación , Anciano de 80 o más Años , Fibras NerviosasRESUMEN
Hypertrophic cardiomyopathy is the most common genetic cardiac disease and is characterized by left ventricular hypertrophy. Although this hypertrophy often associates with sarcomeric gene mutations, nongenetic factors also contribute to the disease, leading to diastolic dysfunction. Notably, this dysfunction manifests before hypertrophy and is linked to hypercontractility, as well as nonuniform contraction and relaxation (myofibril asynchrony) of the myocardium. Although the distribution of hypertrophy in hypertrophic cardiomyopathy can vary both between and within individuals, in most cases, it is primarily confined to the interventricular septum. The reasons for septal thickening remain largely unknown. In this article, we propose that alterations in muscle fiber geometry, present from birth, dictate the septal shape. When combined with hypercontractility and exacerbated by left ventricular outflow tract obstruction, these factors predispose the septum to an isometric type of contraction during systole, consequently constraining its mobility. This contraction, or more accurately, this focal increase in biomechanical stress, prompts the septum to adapt and undergo remodeling. Drawing a parallel, this is reminiscent of how earthquake-resistant buildings are retrofitted with vibration dampers to absorb the majority of the shock motion and load. Similarly, the heart adapts by synthesizing viscoelastic elements such as microtubules, titin, desmin, collagen, and intercalated disc components. This pronounced remodeling in the cytoskeletal structure leads to noticeable septal hypertrophy. This structural adaptation acts as a protective measure against damage by attenuating myofibril shortening while reducing cavity tension according to Laplace Law. By examining these events, we provide a coherent explanation for the septum's predisposition toward hypertrophy.
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Cardiomiopatía Hipertrófica , Humanos , Cardiomiopatía Hipertrófica/fisiopatología , Contracción Miocárdica/fisiología , Animales , Remodelación Ventricular/fisiología , Tabiques Cardíacos/fisiopatología , Tabiques Cardíacos/diagnóstico por imagen , Tabiques Cardíacos/patología , Tabique Interventricular/fisiopatología , Tabique Interventricular/diagnóstico por imagenRESUMEN
As the population ages, the prevalence of heart failure and individuals wearing an implanted cardiac device is increasing. The combination of different underlying pathophysiologies and (the combination of) implanted cardiac devices can become a challenge with regard to the determination of cause and manner of death in such individuals. Additionally, heart disease is frequently associated with mental disease, ranging from anxiety and depression to suicidality and suicide (attempts). At the same time, the correct diagnosis of cause and manner of death is the basis for quality assurance, further therapeutic advances, legal safety, and suicide prevention. By that, an interdisciplinary field between legal medicine, clinicians, and law enforcement opens up. In this field, the different participants can simultaneously benefit from and need each other. For example, legal medicine experts need investigatory results and clinical expertise for the interpretation of readout data of implanted cardiac devices in order to correctly determine the cause of death. A correctly determined cause of death can assist law enforcement and help clinicians to further improve various therapeutic approaches based on correct mortality data collection. In addition, it is the basis for identification of suicides of device carriers, allowing psychological and psychiatric experts to better understand the burden of mental disease in this particular cohort. Against this interdisciplinary background, this manuscript summarizes information about psychiatric comorbidities and suicidality while being on a device. Thereby, basic information on complications and malfunctions of implanted cardiac devices, device-associated deaths with particular emphasis on device manipulation is displayed as basic information needed for correct determination of the cause of death. Also, legal and ethical issues in this field are outlined. The final result is a proposal of an interdisciplinary assessment workflow for a conjoint approach to improve the diagnosis of deaths associated with implanted cardiac devices. It will allow for a differentiation between an individual who died with or due to the device.
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Both particular myocardial locations in the human heart and the canonical transient receptor potential 6 (TRPC6) cation channel have been linked with cardiac pathophysiologies. Thus, the present study mapped TRPC6-protein distribution in select anatomic locations associated with cardiac disease in the context of an orienting pathological assessment. Specimens were obtained from 5 body donors (4 formalin fixation, 1 nitrite pickling salt-ethanol-polyethylene glycol (NEP) fixation; median age 81 years; 2 females) and procured for basic histological stains and TRPC6-immunohistochemistry. The latter was analyzed descriptively regarding distribution and intensity of positive signals. The percentage of positively labelled myocardium was also determined (optical threshold method). Exclusively exploratory statistical analyses were performed. TRPC6-protein was distributed widespread and homogenously within each analyzed sample. TRPC6-immunoreactive myocardial area was comparable regarding the different anatomic regions and sex. A significantly larger area of TRPC6-immunoreactive myocardium was found in the NEP-fixed donor compared to the formalin fixed donors. Two donors with more severe heart disease showed smaller areas of myocardial TRPC6-immunoreactivity overall compared to the other 3 donors. In summary, in the elderly, TRPC6-protein is widely and homogenously distributed, and severe cardiac disease might be associated with less TRPC6-immunoreactive myocardial area. The tissue fixation method represents a potential confounder.
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Three intermediate-range shots from a Browning, model 1955, 7.65 mm caliber, pistol were fired from the driver's seat of a car at a woman in the passenger seat. She sustained three wounds: An, ultimately fatal, penetrating head wound, a graze wound across her forehead, and a tangential, perforating, wound, with bullet entry over the medial sternum and exit through the right flank. Neither postmortem CT nor forensic autopsy discovered bony thoracic injuries or perforations of the thoracoabdominal cavities. There was pulmonary contusion in the medial lobe of the right lung and hemorrhage in the adipose tissue around the right kidney. The tangential bullet had left an almost 40-cm-long wound channel through a pronounced layer of subcutaneous fat. Based on 3D reconstructed CT-data determinations, a straight bullet trajectory between entry and exit wounds would have traversed the abdominothoracic cavities, right lung, and liver. The actual trajectory, however, described a prominent curve, without signs of deflection by bone. Postulated explanations for this unusual bullet track are that the woman was twisting her body in a dynamic scene when the bullet struck; further, due to its shallow angle of incidence on the skin, the bullet was deflected to an intracutaneous path. Additionally, soft tissue resistance may have caused the bullet to yaw. Caution should, thus, be exercised when reconstructing bullet trajectories solely from entry and exist wounds, also for bullet wounds through basically homogenous soft tissues.
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Traumatismos Craneocerebrales , Armas de Fuego , Heridas por Arma de Fuego , Humanos , Femenino , Heridas por Arma de Fuego/diagnóstico por imagen , Balística Forense , AutopsiaRESUMEN
In the frame of an experimental setting, the formation of round-shaped compounded glass fragments on the exit site after gunshots through a windshield was examined. For that purpose, a 9 × 19 mm pistol (HK P30) and two different cartridges containing (a) a full metal jacketed round-nosed projectile and (b) a deformation projectile were used. On the basis of 52 gunshots, the morphology, impact angles and terminal ballistics of occurring compounded glass fragments were examined. The results showed that the compounded glass fragments' morphology allowed for the differentiation of two used projectiles. Fragments were able to cause round-shaped defects in a single cotton layer (T-shirt) with subsequent penetration of up to 2.4 cm into ballistic gelatin (10%, 4 °C). As a function of the projectile type, the compounded glass fragments showed different reproducible impact angles that differed notably from the known conical pattern of expelled glass fragments after bullet penetration. These findings might help to explain the atypical morphology of gunshot wounds with laminated glass as an intermediate target and prevent possible misinterpretations when reconstructing the sequence of events.
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Armas de Fuego , Heridas por Arma de Fuego , Humanos , Balística Forense , Textiles , VidrioRESUMEN
BACKGROUND: The transient receptor potential canonical 6 (TRPC6) channel has been studied in pathologies of the hepatobiliary system. Information on the localization of TRPC6-protein in anatomical and histological structures of the human hepatobiliary system in elderly with and without liver disease is lacking. METHODS: Samples were obtained from twelve nitrite pickling salt-ethanol-polyethylene glycol-fixed corpses of the four anatomical liver lobes, collum and the remaining gallbladder, the common bile duct (gender: 5 females, 41.67%; age [years]: median 84, range 20; postmortem interval before fixation [h]: median 60, range 74.15). Orienting histomorphologic assessment was done in a hematoxylin-eosin stain. Immunohistochemical labelling of TRPC6 was carried out following a cross-evaluation scheme. TRPC6-immunoreactivity was assessed regarding intensity (semi-quantification, three independent observers) and area (optical threshold method). Explorative statistical analyses were performed using R (inter-rater-reliability: Fleiss' kappa; comparisons: Wilcoxon-Rank-sum-test). RESULTS: Extensive autolysis was found in the liver of one and the biliary samples of three corpses. Extensive liver disease was found in 4 corpses, while 8 corpses only showed age-appropriate degeneration. Only the intrahepatic connective tissue showed no TRPC6-immunoreactivity. Individuals with extensively diseased livers exhibited statistically significantly less TRPC6-immunoreactive area in the bile duct and liver tissue while statistically significant more TRPC6-immunoreactive area in the gallbladder compared to individuals with age-appropriate degeneration of the liver only in the respective organ. CONCLUSION: Age-associated degeneration of the hepatobiliary system is likely to be associated with widespread, homogenous TRPC6-expression. Liver disease potentially influences the distribution of TRPC6-protein within the liver and within the biliary tract in elderly.
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Hepatopatías , Canal Catiónico TRPC6 , Anciano , Femenino , Humanos , Cadáver , Expresión Génica , Hepatopatías/genética , Reproducibilidad de los Resultados , Canal Catiónico TRPC6/genética , Masculino , Anciano de 80 o más AñosRESUMEN
Background: During the recent pandemic with the severe acute respiratory syndrome-corona virus2 the first messenger ribonucleic acid (mRNA) vaccines were approved. To facilitate mass vaccination, confidence of the general population in these new vaccines is mandatory, which is in turn strongly dependent on the availability of reliable data on complications. Objective: Summary of the current knowledge on mRNA vaccination-associated myocarditis as a potentially fatal side effect. Methods: Systematic literature review. Results: Diagnostic algorithm for the postmortem diagnosis of mRNA vaccination-associated myocarditis. Conclusion: Autopsy series of fatalities following mRNA SARS-CoV2 vaccination up to 6 weeks with subsequent sophisticated and interdisciplinary work-up are necessary to complement clinical data on vaccination-associated myocarditis, especially regarding the incidence of fatal courses. Supplementary Information: The online version of this article (10.1007/s00194-022-00587-9) includes a PDF file with supplemental clinical features.
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We sought to determine whether there are differences in transforming growth factor-beta (TGFß) signaling in aneurysms associated with bicuspid (BAV) and unicuspid (UAV) aortic valves versus normal aortic valves. Ascending aortic aneurysms are frequently associated with BAV and UAV. The mechanisms are not yet clearly defined, but similarities to transforming growth factor-beta TGFß vasculopathies (i.e. Marfan, Loeys-Dietz syndromes) are reported. Non-dilated (ND) and aneurysmal (D) ascending aortic tissue was collected intra-operatively from individuals with a TAV (N = 10ND, 10D), BAV (N = 7ND, 8D) or UAV (N = 7ND, 8D). TGFß signaling and aortic remodeling were assessed through immuno-assays and histological analyses. TGFß1 was increased in BAV/UAV-ND aortas versus TAV (P = 0.02 and 0.04, respectively). Interestingly, TGFß1 increased with dilatation in TAV (P = 0.03) and decreased in BAV/UAV (P = 0.001). In TAV, SMAD2 and SMAD3 phosphorylation (pSMAD2, pSMAD3) increased with dilatation (all P = 0.04) and with TGFß1 concentration (P = 0.04 and 0.03). No relationship between TGFß1 and pSMAD2 or pSMAD3 was observed for BAV/UAV (all P > 0.05). pSMAD3 increased with dilatation in BAV/UAV aortas (P = 0.01), whereas no relationship with pSMAD2 was observed (P = 0.56). Elastin breaks increased with dilatation in all groups (all P < 0.05). In TAV, elastin degradation correlated with TGFß1, pSMAD2 and pSMAD3 (all P < 0.05), whereas in BAV and UAV aortas, elastin degradation correlated only with pSMAD3 (P = 0.0007). TGFß signaling through SMAD2/SMAD3 contributes to aortic remodeling in TAV, whereas TGFß-independent activation of SMAD3 may underlie aneurysm formation in BAV/UAV aortas. Therefore, SMAD3 should be further investigated as a therapeutic target against ascending aortic dilatation in general, and particularly in BAV/UAV patients.
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Enfermedades de la Aorta , Elastina , Enfermedades de la Aorta/patología , Dilatación , Dilatación Patológica , Enfermedades de las Válvulas Cardíacas , Humanos , Proteína smad3 , Factor de Crecimiento Transformador beta , Factores de Crecimiento TransformadoresRESUMEN
Background Quadricuspid aortic valve is rare and occasionally associated with aortic regurgitation and ascending aortic dilatation. Recent studies suggest an association of aortic regurgitation with ascending aortic medial degeneration. Case Description Histologic evaluation of ascending aortic tissue of two individuals with regurgitant quadricuspid aortic valve, one dilated, one non-dilated, yielded comparable degeneration in the Media. Conclusion Regurgitation of quadricuspid aortic valve may lead to the degeneration of Tunica media of the ascending aorta.
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Introduction: Multiple cardiovascular conditions can lead to unexpected fatality, which is defined as sudden cardiac death. One of these potentially underlying conditions is aortic regurgitation, which can be caused by discrete changes of the geometry of the proximal aorta. To analyze aortic valve competency and furthermore to elucidate underlying pathological alterations of the coronary arteries and the vasa vasorum a perfusion method to simulate a diastolic state was designed. Material and methods: A postmortem approach with retrograde perfusion of the ascending aorta with methylene blue was applied to three bodies. The procedure comprised cannulation of the brachiocephalic trunk, clamping of the aortic arch between brachiocephalic trunk and left carotid artery, infusion of 250 ml of methylene blue, and optical clearing of the superficial tissue layers after perfusion. Organs were examined directly following perfusion and after optical clearing. Results: Assessment and visualization of aortic valve competency and the vasa vasorum were possible in all three instances. Visualization of the coronary perfusion was impaired by postmortem thrombus formation. Optical clearing did not provide additional information. Discussion: The method presented here is a time- and cost-efficient way of visualizing aortic valve competency and the vasa vasorum. The visualization of the vasa vasorum highlights the potential of this method in basic research on diseases of the great arteries and coronaries. However, for a time-efficient functional analysis of the coronaries, other methods must be applied.
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BACKGROUND: We have proposed an external stabilization technique to minimize autograft dilatation after the Ross operation. This study analyzed autograft function and root dimensions after root replacement with and without external root support. METHODS: Between October 1995 and February 2021, 185 adult patients (73% male; age, 38 ± 9 years) underwent a Ross operation as full-root replacement, 136 with support and 49 without support. Autograft function and root dimensions were determined echocardiographically. Median follow-up was 3.4 years (interquartile range, 1.13-14.74 years) and was 95% complete. Survival and freedom from reoperation were calculated. Changes in autograft root dimensions were analyzed using mixed-effect models. RESULTS: Survival (95%) and freedom from autograft reoperation (94%) at 15 years were higher with than without support (P = .003 or P = .004). In the first 5 years, patients with support showed an indexed root size progression of 0.712 mm/(y â m) (P = .003) compared with 1.554 mm/(y â m) (P = .001) without. Progression rates were higher for patients without stabilization (P = .045). After 5 years, progression rates were similar in both groups at 0.248 mm/(year â m) (P < .001) but with persistent a difference between the groups. CONCLUSIONS: The Ross procedure as full-root replacement is associated with a relevant rate of autograft dilatation and reoperation. The use of external root stabilization may reduce autograft dilatation and is associated with improved survival and durability.
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Insuficiencia de la Válvula Aórtica , Procedimientos Quirúrgicos Cardíacos , Válvula Pulmonar , Adulto , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Autoinjertos , Procedimientos Quirúrgicos Cardíacos/métodos , Dilatación Patológica/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Válvula Pulmonar/trasplante , Reoperación , Trasplante AutólogoRESUMEN
BACKGROUND: Valve failure may occur after valve-sparing aortic root replacement. Little is known about the exact mechanisms of failure. This study analyzed reoperations after aortic root remodeling to determine failure modes, operative risk, and long-term outcome. METHODS: Between November 1995 and December 2019, 1084 patients were treated by root remodeling. Of these, 54 (49 male; aged 8 to 79 years) underwent reoperation for valve failure (1 week to 16 years postoperatively). The indications for reoperation were aortic regurgitation (n = 39), aortic stenosis (n = 6), endocarditis (n = 7), or ventricular septal defect (n = 2). The main causes of valve failure were cusp repair failure (n = 29), endocarditis (n = 7), and cusp retraction (n = 8). The patients were treated by valve replacement (n = 40) or cusp repair (n = 14). In 6 individuals, combined replacement of valve and root was performed. All 54 patients were followed up (mean, 69 ± 54 months after reoperation), and 1 patient was lost to follow-up. RESULTS: No patient died in the hospital or had atrioventricular block development; 12 patients died late, with 10- and 15-year survivals of 87% ± 5.1% and 64% ± 10.6%, respectively. Of the 14 patients who underwent repeat cusp repair, 7 (50%) are still alive with stable valve function, 17 months to 15 years after their reoperation. Eleven patients required a second reoperation leading to a freedom from repeat reintervention rate of 68% ± 9.7% at 15 years. CONCLUSIONS: The main causes of failure of root remodeling are cusp related. Reoperations can be performed with low morbidity and mortality. In selected patients, isolated cusp repair may be an option.
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Insuficiencia de la Válvula Aórtica , Endocarditis , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Endocarditis/cirugía , Humanos , Masculino , Reoperación/efectos adversos , Reimplantación/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Preservation or repair of the aortic valve has evolved dynamically in the past 20 years. It leads to a high freedom from valve-related complications if an adequate valve durability can be achieved; it may possibly also improve survival. To date, little structured information is available about which valves can be repaired and which should better be replaced. RECENT FINDINGS: For surgical decision-making, the size of the aortic root is important and the anatomy of the aortic valve must be considered. In the presence of root aneurysm, most tricuspid and bicuspid aortic valves can be preserved. In aortic regurgitation and normal aortic dimensions, the majority of tricuspid and bicuspid aortic valves can be repaired with good long-term durability. In bicuspid aortic valves, the morphologic characteristics must be taken into consideration. Unicuspid and quadricuspid aortic valves can be repaired in selected cases. Generally, cusp calcification is a sign of a poor substrate for repair; the same is true for cusp retraction and cusp destruction due to active endocarditis. They are associated with limited valve durability. Using current concepts, many non-calcified aortic valves can be repaired. Modern imaging, in particular three-dimensional transesophageal echocardiography (TEE), should be able to define repairable aortic valves with a high probability.
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Insuficiencia de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Aorta , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/cirugía , Humanos , ReoperaciónRESUMEN
Aortic valve repair and valve-preserving root replacement have evolved into increasingly practiced procedures. With increasing experience, the need for an annuloplasty has become more evident, at least for pathologies that involve annular dilatation. To understand the effect of an aortic annuloplasty, it is necessary to know the details of aortic valve and root anatomy. Geometrically, the functional annulus is best defined as the virtual basal ring, ie, plane of the cusp nadirs. The sinotubular diameter also influences the aortic valve form, at least in tricuspid valves. Different annuloplasty concepts have been developed for isolated valve repair or in combination with root remodeling, such as subcommissural sutures, suture annuloplasty, external, and internal rings. Subcommissural sutures do not consistently provide durable annular stabilization. More positive results have been published for circular approaches, ie, suture annuloplasty, external, or internal rings. The results of different techniques are difficult to judge because most outcome data have not been analyzed with control of confounding predictors of repair failure. The evidence that annuloplasty improves aortic valve function and repair durability is best documented for isolated bicuspid aortic valve repair. In summary, the addition of annuloplasty to aortic valve reconstruction is probably a useful tool to improve valve competence and stabilize the repair. This is best documented for isolated bicuspid valve repair and circular approaches. The relative benefit of individual concepts is difficult to judge because of lack of both control groups and control of confounding factors.
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OBJECTIVES: The unicuspid aortic valve (UAV) is a rare cardiac malformation and is associated with the formation of ascending aortic aneurysms. To characterize its associated aortic wall changes, normal and aneurysmatic ascending aortic wall specimens were analysed, focusing on the potential mechanisms of aneurysm formation. Patients with tricuspid aortic valve (TAV) served as controls. METHODS: In a retrospective observational study, 74 specimens (dilated and non-dilated aortas; individuals with UAV and TAV) obtained intraoperatively were studied. Standard stains and immunohistochemical labelling of cleaved caspase-3, cluster of differentiation 31 and endothelial nitric oxide synthase (eNOS) were performed to assess the degree of apoptosis, distribution of eNOS within the aortic wall, smooth muscle cell (SMC) nuclei loss and mucoid extracellular matrix accumulation (MEMA). RESULTS: Deeper ingrowth of vasa vasorum was found in dilated aortas. Interestingly, eNOS was expressed mostly in vasa vasorum. More apoptosis was seen in UAV aortas compared to TAV aortas (P < 0.001). Both UAV and TAV aortas were comparable regarding SMC nuclei loss (P = 0.419). In dilated compared to non-dilated aortas regardless valve morphology SMC nuclei loss was increased (P = 0.005) and more pronounced translamellar MEMA was present (P = 0.011). The highest grade of distribution (P = 0.043) and the highest severity (P = 0.005) regarding MEMA were seen in TAV dilated specimens compared to UAV dilated specimens. CONCLUSIONS: Aneurysms with UAV show increased apoptosis, the role of which is unclear. Strikingly, more severe MEMA was found in TAV aneurysms compared to UAV aneurysms. Thus, UAV-associated aortic wall changes and resulting aneurysm may be less aggressive than aneurysms with TAV.
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Aneurisma de la Aorta , Enfermedades de las Válvulas Cardíacas , Aorta , Válvula Aórtica , HumanosRESUMEN
We report a case in whom aortic wrapping had been performed for aortic dilatation. Ten years later, further progression of aortic root diameter was documented (root size of 66 mm). We performed complete replacement of the proximal aorta. Macroscopically and microscopically, there was extreme degeneration and thinning of the aorta under the graft.
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Aorta , Enfermedades de la Aorta , Aorta/diagnóstico por imagen , Aorta/cirugía , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/cirugía , Válvula Aórtica , Dilatación Patológica , HumanosRESUMEN
OBJECTIVE: The probability of aortic complications in patients with bicuspid aortic valve is higher in association with aortic regurgitation (AR) compared with aortic stenosis (AS) or normally functioning valves. The objective of this study was to determine whether this is related to the specific characteristics of aneurysmatic dilatation that includes AR or whether AR itself has a negative impact on the aortic wall, independent of aneurysmatic dilatation. Approach and Results: Nondilated aortic specimens were harvested intraoperatively from individuals with tricuspid aortic valves and either AS (n=10) or AR (n=16). For controls, nondilated aortas were harvested during autopsies from individuals with tricuspid aortic valves and no evidence of aortic valve disease (n=10). Histological and immunohistochemical analyses revealed that compared with control aortas, overall medial degeneration was more severe in AR-aortas (P=0.005) but not AS-aortas (P=0.23). This pathological remodeling included mucoid extracellular matrix accumulation (P=0.005), elastin loss (P=0.003), elastin fragmentation (P=0.008), and decreased expression of fibrillin (P=0.003) and collagen (P=0.008). Furthermore, eNOS (endothelial nitric oxide synthase) expression was decreased in the intima (P=0.0008) and in vasa vasorum (P=0.004) of AR-aortas but not AS-aortas (all P>0.05). Likewise, subendothelial apoptosis was increased in AR-aortas (P=0.03) but not AS-aortas (P=0.50). CONCLUSIONS: AR has a negative effect on the nondilated ascending aortic wall. Accordingly, our results support the need for more detailed studies of the aortic wall in relation to aortic valve disease and may ultimately lead to more aggressive clinical monitoring and/or surgical criteria for patients with relevant AR. Graphic Abstract: A graphic abstract is available for this article.
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Aorta/patología , Insuficiencia de la Válvula Aórtica/patología , Remodelación Vascular , Adulto , Anciano , Aorta/metabolismo , Insuficiencia de la Válvula Aórtica/metabolismo , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/cirugía , Apoptosis , Estudios de Casos y Controles , Colágeno/metabolismo , Dilatación Patológica/metabolismo , Dilatación Patológica/patología , Elastina/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Fibrilinas/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/metabolismo , Remodelación Vascular/fisiología , Adulto JovenRESUMEN
Objectives: Certain aortic valve malformations predispose to ascending aortic aneurysm, although the mechanisms are incompletely understood. The aim of this study was to determine whether turbulence across the unicuspid aortic valve (UAV) contributes to regional differences in endothelial nitric oxide (eNOS) signaling in the ascending aortic wall. Methods: Samples were collected intraoperatively from the convex and concave ascending aortic wall from 64 patients with tricuspid aortic valves (TAVs; 25 nondilated, 17 dilated), or UAVs (9 nondilated, 13 dilated). Results: In normal-sized aortas, eNOS protein was decreased in UAV compared with TAV (P = .02) whereas mRNA was similar (P = .62). eNOS protein was increased in UAV-dilated aortas compared with UAV-nondilated aortas (P = .04), whereas dilatation had no impact on eNOS protein levels in TAV aortas (P = .73). Comparing only aneurysmal aortas, we found no difference in eNOS mRNA or protein between dilated TAV and UAV aortas (P = .26, P = .76). For eNOS mRNA and protein levels in normal and dilated UAV-associated aortas, no differences were found between concavity and convexity (all P > .05). This differed from dilated TAV aortas, which showed decreased eNOS mRNA in the convexity (P = .004) whereas eNOS protein levels were similar (P = .75). Conclusions: eNOS downregulation is observed in the UAV-associated ascending aorta and is apparently independent of dilatation. No regional differences were found, however, which would be expected if eNOS changes occur due to wall shear stress. This implies a congenital defect in eNOS signaling that may be stronger than turbulence-induced expression patterns. Further research should define the role of eNOS in aortopathy associated with aortic valve disease.