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1.
Arch Plast Surg ; 51(1): 42-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38425846

RESUMO

Background Increasing concerns regarding the safety of textured surface implants have resulted in surgeons transitioning from textured tissue expanders (TEs) to smooth TEs. Given this change has only recently occurred, this study evaluated outcomes between smooth and textured TEs. Methods Women who underwent two-stage breast reconstruction using TEs from 2013 to 2022 were included. TE-specific variables, perioperative information, pain scores, and complications were collected. Chi-squared, t -test, and linear regression analyses were performed. Results A total of 320 patients received a total of 384 textured and 152 smooth TEs. Note that 216 patients received bilateral reconstruction. TEs were removed in 9 cases. No significant differences existed between groups regarding comorbidities. Smooth TEs had a higher proportion of prepectoral placement ( p < 0.001). Smooth TEs had less fills (3 ± 1 vs. 4 ± 2, p < 0.001), shorter expansion periods (60 ± 44 vs. 90 ± 77 days, p < 0.001), smaller expander fill volumes (390 ± 168 vs. 478 ± 177 mL, p < 0.001), and shorter time to exchange (80 ± 43 vs. 104 ± 39 days, p < 0.001). Complication rates between textured and smooth TEs were comparable. Smooth TE had a greater proportion of TE replacements ( p = 0.030). On regression analysis, pain scores were more closely associated with age ( p = 0.018) and TE texture ( p = 0.046). Additional procedures at time of TE exchange ( p < 0.001) and textured TE ( p = 0.017) led to longer operative times. Conclusion As many surgeons have transitioned away from textured implants, our study shows that smooth TEs have similar outcomes to the textured alternatives.

2.
Plast Reconstr Surg ; 149(4): 731e-742e, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35171849

RESUMO

BACKGROUND: Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains unclear. METHODS: Untreated Pfeiffer syndrome patients (n = 31) and normal control subjects (n = 43) were compared. Craniometric and volumetric analyses related to the orbital and periorbital anatomy were performed using Materialise (Leuven, Belgium) software. RESULTS: Overall, orbital cavity volume of Pfeiffer patients is reduced by 28 percent (p < 0.001), compared to normal, starting before 3 months of age (p = 0.004). Globe volume was diminished by 10 percent (p = 0.041) before 3 months of age, yet tended to catch up thereafter. However, the retrobulbar soft-tissue volume remained smaller beyond 1 year of age (17 percent, p = 0.003). Globe volume projection beyond the bony orbit increased in all observed ages (82 percent, p < 0.001). The volumes of sphenoid bone, maxilla, and mandible proportionately were restricted by 24 to 25 percent (p = 0.003 to 0.035) before 3 months of age. The volume of maxilla and mandible gradually approximate normal; however, the sphenoid bone volume in Pfeiffer patients remains less than normal (p = 0.002) into childhood. The anteroposterior length of both the zygoma and the maxilla was reduced by 14 percent (p < 0.001). Anterior positioning of the zygoma is less by 23 percent (p < 0.001) in Pfeiffer patients overall, with anterior positioning of maxilla reduced similarly by 23 percent (p < 0.001). CONCLUSIONS: Pfeiffer syndrome patients develop decreased retrobulbar soft-tissue and globe volume, along with a restricted orbital cavity volume in infancy. Significant hypoplasia of the sphenoid bone is associated with more severe central facial (maxilla) retrusion, compared to lateral facial structures (zygoma). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Acrocefalossindactilia , Acrocefalossindactilia/complicações , Acrocefalossindactilia/diagnóstico por imagem , Cefalometria , Criança , Humanos , Maxila/anatomia & histologia , Órbita/anormalidades , Zigoma
3.
J Reconstr Microsurg ; 38(2): 160-167, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34284504

RESUMO

BACKGROUND: Surgical drains are routinely used following autologous reconstruction, but are often cited as the leading cause of peri-operative discomfort. This study defined routine drain use duration and assessed the risk factors for prolonged breast and abdominal drain use during microvascular breast reconstruction, measures which have never previously been defined. METHODS: Patients who underwent an abdominal microvascular free flap were included. Demographics, comorbidities, and operation-related characteristics were retrospectively collected in a prospectively maintained database. Statistical analysis utilized chi-square independent t-test, and linear regression analyses. RESULTS: One hundred forty-nine patients comprising 233 breast flaps were included. Average breast and abdominal drain duration were 12.9 ± 3.9 and 17.7 ± 8.2 days, respectively. Prolonged breast and abdominal drain duration were defined as drain use beyond the 75th percentile at 14 and 19 days, respectively. Multivariable regression revealed hypertension was associated with an increased breast drain duration by 1.4 days (p = 0.024), axillary dissection with 1.7 days (p = 0.026), African-American race with 3.1 days (p < 0.001), Hispanic race with 1.6 days (p = 0.029), return to the OR with 3.2 days (p = 0.004), and each point increase in BMI with 0.1 days (p = 0.028). For abdominal drains, each point increase in BMI was associated with an increased abdominal drain duration by 0.3 days (p = 0.011), infection with 14.4 days (p < 0.001), and return to the OR with 5.7 days (p = 0.007). CONCLUSION: Elevated BMI, hypertension, and axillary dissection increase risk for prolonged breast drain requirement in autologous reconstruction. African-American and Hispanic populations experience prolonged breast drain requirement after controlling for other factors, warranting further study.


Assuntos
Retalhos de Tecido Biológico , Mamoplastia , Mama , Drenagem , Humanos , Estudos Retrospectivos
4.
Plast Reconstr Surg ; 148(1): 145-156, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34181610

RESUMO

BACKGROUND: Little is known about the detailed growth of the cranial fossae, even though they provide an important structural connection between the cranial vault and the facial skeleton. This study details the morphologic development of isolated cranial vault synostosis and associated syndromes on cranial fossa development. METHODS: A total of 125 computed tomographic scans were included (nonsyndromic bicoronal synostosis, n = 36; Apert syndrome associated with bicoronal synostosis, n = 24; Crouzon syndrome associated with bicoronal synostosis, n = 11; and controls, n = 54). Three-dimensional analyses were produced using Materialise software. RESULTS: The regional anterior and middle cranial fossae volumes of nonsyndromic bicoronal synostosis are characterized by significant increases of 43 percent (p < 0.001) and 60 percent (p < 0.001), respectively, and normal posterior cranial fossa volume. The cranial fossae depths of nonsyndromic bicoronal synostosis were increased, by 37, 42, and 21 percent (all p < 0.001) for anterior, middle, and posterior cranial fossae, respectively, accompanying the shortened cranial fossae lengths. The volume and morphology of all cranial fossae in Apert syndrome nearly paralleled nonsyndromic bicoronal synostosis. However, Crouzon syndrome had reduced depths of cranial fossae, and more restricted fossa volumes than both Apert syndrome and nonsyndromic bicoronal synostosis. CONCLUSIONS: Cranial vault suture synostosis is likely to be more influential on cranial fossae development than other associated influences (genetic, morphologic) in Apert and Crouzon syndromes. Isolated Apert syndrome pathogenesis is associated with an elongation of the anterior cranial fossa length in infants, whereas in Crouzon syndrome, there is a tendency to reduce cranial fossa depth, suggesting individual adaptability in cranial fossae development related to vault synostosis.


Assuntos
Acrocefalossindactilia/complicações , Disostose Craniofacial/complicações , Craniossinostoses/complicações , Base do Crânio/crescimento & desenvolvimento , Acrocefalossindactilia/diagnóstico , Adolescente , Criança , Pré-Escolar , Disostose Craniofacial/diagnóstico , Craniossinostoses/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X
5.
Ann Plast Surg ; 87(1): 59-64, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34133365

RESUMO

OBJECTIVE: Previous studies have explored the restricted nasopharyngeal airway in Apert syndrome patients. This study aims to investigate the segmented airway volume changes with age and directly analyze their correlations with subcranial dimensions and angulations. METHODS: Ninety-seven preoperative computed tomography scans (Apert, n = 44; control, n = 53) were included in this study, and divided into 5 age-related subgroups. Computed tomography scans were measured using Mimics and 3-matics software. RESULTS: Before 6 months of age, the nasal cavity in Apert syndrome is reduced by 47% (P = 0.002), which gradually approximates normal thereafter; however, there remained a 30% reduction, compared with controls. It is highly correlated with the anteroposterior length of subcranial space, and the position of maxilla and palate. The pharyngeal airway volume in Apert syndrome patients, younger than 6 months, was larger than normal by 129% (P = 0.013). However, between 2 and 6 years of age, the pharyngeal airway becomes smaller than normal, with a 57% (P = 0.010) reduction in childhood and 52% (P = 0.005) in adolescence. It is closely correlated with the intercondylar and intergonial widths. CONCLUSIONS: Airway compromise in Apert syndrome patients is attributable more to the nasal cavity in infants, but in the older child, it is the pharyngeal region. The restricted nasal airway in Apert syndrome is correlated with the subcranial space length and width, but independent of cranial base flexion. The pharyngeal airway volume in Apert syndrome is not as highly correlated with craniofacial morphology. Rather, it is impacted by the growth of mandible, which often requires surgical intervention later in childhood.


Assuntos
Acrocefalossindactilia , Acrocefalossindactilia/diagnóstico por imagem , Acrocefalossindactilia/cirurgia , Adolescente , Cefalometria , Criança , Humanos , Lactente , Mandíbula , Maxila , Faringe/diagnóstico por imagem , Faringe/cirurgia , Base do Crânio
6.
J Craniofac Surg ; 32(2): 581-586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704985

RESUMO

BACKGROUND: Pfeiffer syndrome is a rare syndromic craniosynostosis disorder, with a wide range of clinical manifestations. This study aims to investigate the structural abnormalities of cranial fossa and skull base development in Pfeiffer patients, to provide an anatomic basis for surgical interventions. METHOD: Thirty preoperative CT scans of Pfeiffer syndrome patients were compared to 35 normal controls. Subgroup comparisons, related to differing suture synostosis, were performed. RESULTS: Overall, the volume of anterior and middle cranial fossae in Pfeiffer patients were increased by 31% (P < 0.001) and 19% (P = 0.004), versus controls. Volume of the posterior fossa in Pfeiffer patients was reduced by 14% (P = 0.026). When only associated with bicoronal synostosis, Pfeiffer syndrome patients developed enlarged anterior (68%, P = 0.001) and middle (40%, P = 0.031) fossae. However, sagittal synostosis cases only developed an enlarged anterior fossa (47%, P < 0.001). The patients with solely bilateral squamosal synostosis, developed simultaneous reduced anterior, middle and posterior cranial fossae volume (all P ≤ 0.002). The overall skull base angulation, measured on both intracranial and subcranial surfaces, grew normally. CONCLUSION: Enlarged anterior cranial fossae in Pfeiffer syndrome children is evident, except for the squamosal synostosis cases which developed reduced volume in all fossae. Volume of the middle cranial fossa is influenced by associated cranial vault suture synostosis, specifically, sagittal synostosis cases develop normal middle fossa volume, while the bicoronal cases develop increased middle fossa volume. Posterior cranial fossa development is restricted by shortened posterior cranial base length. Surgical intervention in Pfeiffer syndrome patients optimally should be indexed to different suture synostosis.


Assuntos
Acrocefalossindactilia , Craniossinostoses , Acrocefalossindactilia/diagnóstico por imagem , Criança , Fossa Craniana Anterior , Fossa Craniana Posterior/diagnóstico por imagem , Suturas Cranianas/diagnóstico por imagem , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Humanos , Lactente , Crânio , Base do Crânio/diagnóstico por imagem
7.
Facial Plast Surg Aesthet Med ; 23(3): 191-197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33577380

RESUMO

Background: Obstructive sleep apnea is common in patients with Crouzon syndrome, yet it may be caused by multiple factors. This study aims to investigate the natural history of airway development in preoperative Crouzon patients, from infants to adults. Methods: Preoperative computed tomography (CT) scans (Crouzon syndrome, n = 73; control, n = 87) were divided into five age subgroups. CT scans were measured using Materialise software. Results: Before 6 months of age, nasal airway volume in patients with Crouzon syndrome was smaller than normal by 37% (p = 0.002), and the cross-sectional area at the choana reduced by 45% (p < 0.001). The reduction of nasal airway volume and cross-sectional area reached their nadir at 2 years of age, with shortening of 44% and 63% (both p < 0.001), respectively. They gradually caught up to normal dimensions after 6 years of age. Between 2 and 6 years, the pharyngeal airway in patients with Crouzon syndrome reduced 44% (p = 0.011) compared with controls. However, the airway cross-sectional area at condylion and gonion levels was less than normal, before 6 months (35%, p = 0.024) and (44%, p = 0.006) after 2 years of age, respectively. This reduction remains into adulthood. Conclusion: Nasal airway volume is more limited in children with Crouzon syndrome who are younger than 2 years of age. Whereas after 2 years of age, the pharyngeal airway develops significant volume restriction, leading to timing and specific treatment area foci based on the site of temporal maximal constriction.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Disostose Craniofacial/fisiopatologia , Nariz/crescimento & desenvolvimento , Faringe/crescimento & desenvolvimento , Adolescente , Adulto , Fatores Etários , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Disostose Craniofacial/complicações , Disostose Craniofacial/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nariz/anormalidades , Nariz/diagnóstico por imagem , Nariz/fisiopatologia , Tamanho do Órgão , Faringe/anormalidades , Faringe/diagnóstico por imagem , Faringe/fisiopatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
J Craniofac Surg ; 32(3): 855-858, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941216

RESUMO

PURPOSE: Maxillofacial trauma is treated by two medical specialties, plastic surgery (PRS) and otolaryngology (ENT). Differences in training exposure and practice patterns exist between specialties, but their respective outcomes have never been compared. METHODS: Mandible fracture data were reviewed from the National Surgical Quality Improvement Program from 2005 to 2016. Demographics variables, repair types, and adverse outcomes were compared between PRS and ENT. RESULTS: From 2005 to 2016, one thousand two hundred eighty-two cases were identified with 756 cases managed by ENT and 526 cases managed by PRS. Mean patient age was 34.6 years for both specialties (P = 0.95). Patient demographics between both cohorts were not statistically different except for higher rates of hypertension among ENT patients (10.2% for ENT versus 6.7% for PRS, P = 0.027) and higher rates of smoking history among PRS patients (46.8% versus 52.3%, P = 0.055). Mean operative time (131.3 versus 124.0 min, P = 0.090) had a trend toward being longer for ENT and mean length of stay (1.3 versus 2.0, P = 0.002) was significantly longer for PRS. Despite a greater proportion of high ASA class patients in the ENT group (P = 0.012) and patients with dirty/infected wounds in the PRS group (P = 0.013), there were no significant differences in 30-day readmission rates, 30-day reoperation rates, or wound infection rates. CONCLUSIONS: No significant differences in 30-day readmission rates, reoperation rates, or wound infection rates for mandible fracture management exist between specialties. Despite differences in training between PRS and ENT, both specialties have comparable perioperative outcomes for mandible fracture management.


Assuntos
Fraturas Mandibulares , Cirurgia Plástica , Adulto , Humanos , Mandíbula , Fraturas Mandibulares/cirurgia , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
9.
J Craniofac Surg ; 32(1): 67-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32868725

RESUMO

BACKGROUND: Little is known about the detailed growth of the sphenoidal and temporal bones, even though they contribute significantly to the cranial base and cranial fossa skeletons. They also serve to connect the cranial vault with facial structure. This study details their morphologic development in isolated bicoronal synostosis and associated syndromes. METHODS: Eighty-one CT scans were included (nonsyndromic bicoronal synostosis, n = 28; Apert syndrome associated with bicoronal synostosis, n = 19; Crouzon syndrome associated with bicoronal synostosis, n = 8; and controls, n = 26), and measured using Materialize software. RESULTS: Sphenoidal and temporal bone volumes in nonsyndromic bicoronal synostosis are reduced 23% (P = 0.005) and 24%(P = 0.003) at 6 months of age, compared to controls. Apert and Crouzon syndrome patients developed similar reduced volumes. The greater wing of the sphenoid and pterygoid processes in nonsyndromic bicoronal synostosis are initially inferiorly rotated at 2 months of age, by 9.60° (P = 0.002) and 4.33° (P = 0.023), respectively. In Apert syndrome, these rotations were reduced by 4.82° (P = 0.003) and 12.60° (P < 0.001), (like Crouzon syndrome). However, in Apert syndrome, the length of pterygoid processes is shortened by 11% (P = 0.018) compared to nonsyndromic bicoronal synostosis. Crouzon syndrome skulls did not develop a statistically significant shortening relative to nonsyndromic bicoronal synostosis. Mediolateral expansion of the sphenoid in nonsyndromic bicoronal synostosis was less than normal (P = 0.023), and it was further reduced in syndromic skulls. CONCLUSION: Isolated bicoronal synostosis tends to reduce the volume of sphenoidal and temporal bones, and inferior and posterior rotation of the entire sphenoid. Syndromic conditions restrict sphenoidal rotation, and limit the expansion of sphenoidal greater wing and pterygoid plate.


Assuntos
Disostose Craniofacial , Craniossinostoses , Acrocefalossindactilia/diagnóstico por imagem , Disostose Craniofacial/diagnóstico por imagem , Craniossinostoses/diagnóstico por imagem , Humanos , Osso Esfenoide/diagnóstico por imagem , Síndrome
10.
Pediatr Surg Int ; 36(11): 1345-1352, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918623

RESUMO

BACKGROUND: Steroid use predisposes adult patients to increased perioperative complications including wound dehiscence and delayed wound healing. A similar large study investigating the perioperative impact of steroid use in pediatric patients has not been performed. METHODS: The National Surgical Quality Improvement Project Pediatric Database was queried from 2012-2017 to identify patients who received steroid preoperatively. Patient demographics, comorbidities, surgical variables, and outcomes were compared between cohorts. Patients were propensity score matched and thirty-day adverse events were compared. RESULTS: Of 425,251 pediatric surgery patients, 9716 (2.3%) received preoperative steroids. Pediatric patients treated with steroids were older and had more comorbidities. After propensity score matching, the steroid population had a significantly higher rate of adverse events, including prolonged hospital stay (15.3% vs. 9.1%, p < 0.001), seizure (0.9% vs. 0.4%, p < 0.001), readmission (14.4% vs. 9.2%, p < 0.001), and death (2.2% vs. 1.1%, p < 0.001). CONCLUSION: Preoperative steroid use is independently associated with increased 30-day postoperative adverse events among pediatric patients. Given the significant impact of steroid use on surgical outcomes, the risks and benefits of steroid treatment in children receiving surgery should be carefully evaluated.


Assuntos
Glucocorticoides/efeitos adversos , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Tempo de Internação/tendências , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Estados Unidos/epidemiologia
11.
Plast Reconstr Surg ; 146(3): 599-610, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32842109

RESUMO

BACKGROUND: The association of isolated craniosynostosis and the influence of syndromic forms confound the understanding of craniofacial morphologic development. This study attempts to clarify the individual influences of isolated bicoronal synostosis, Apert syndrome, and Crouzon syndromes on skull base morphology. METHODS: One hundred seventeen computed tomographic scans were included (nonsyndromic bicoronal synostosis, n = 36; Apert syndrome with bicoronal synostosis, n = 25; Crouzon syndrome with bicoronal synostosis, n = 11; controls, n = 45). Cephalometric measurements were analyzed using Materialise software. RESULTS: Nonsyndromic bicoronal synostosis patients developed a shortened cranial base length, with a significantly shortened distance between nasion and sella (p = 0.005). The cranial base angles of nonsyndromic bicoronal synostosis in both the cranial side (N-S-BA) and facial side (N-SO-BA) increased significantly, by 17.04 degrees (p < 0.001) and 11.75 degrees (p < 0.001), respectively. However, both the N-S-BA and N-SO-BA angles of Apert syndrome and Crouzon syndrome were narrowed more than that of nonsyndromic bicoronal synostosis [by 12.11 degrees (p < 0.001) and 12.44 degrees (p < 0.001), respectively, in Apert syndrome; and by 11.66 degrees (p = 0.007) and 13.71 degrees (p = 0.007), respectively, in Crouzon syndrome]. However, there is no statistically significant difference of these two angles between Apert syndrome and Crouzon syndrome, when they were only associated with bicoronal synostosis. Contrary to the relatively normal subcranial space of nonsyndromic bicoronal synostosis, both Apert and Crouzon syndromes developed a reduced subcranial space. CONCLUSIONS: Isolated bicoronal synostosis resulted in a flattened cranial base, whereas Apert syndrome and Crouzon syndrome developed a normal cranial base angle when only associated with bicoronal synostosis. The syndromic skulls had additional significantly reduced subcranial space.


Assuntos
Acrocefalossindactilia/diagnóstico por imagem , Suturas Cranianas/diagnóstico por imagem , Disostose Craniofacial/diagnóstico , Base do Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Cefalometria/métodos , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
12.
BMJ Case Rep ; 13(5)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32381529

RESUMO

Although sickle cell disease has long been viewed as a contraindication to free flap transfer, little data exist evaluating complications of microsurgical procedures in the sickle cell trait patient. Reported is the case of a 55-year-old woman with sickle cell trait who underwent a deep inferior epigastric perforator microvascular free flap following mastectomy. The flap developed signs of venous congestion on postoperative day 2 but was found to have patent arterial and venous anastomoses on exploration in the operating room. On near-infrared indocyanine green angiography, poor vascular flow was noted despite patent anastomoses and strong cutaneous arterial Doppler signals. Intrinsic microvascular compromise or sickling remains a risk in the sickle cell trait population as it does for the sickle cell disease population. Just like in sickle cell disease patients, special care should be taken to optimise anticoagulation and minimise ischaemia-induced sickling for patients with sickle cell trait undergoing microsurgery.


Assuntos
Neoplasias da Mama/cirurgia , Hiperemia/etiologia , Microcirurgia , Retalho Perfurante/irrigação sanguínea , Traço Falciforme/complicações , Anticoagulantes/uso terapêutico , Artérias Epigástricas/transplante , Feminino , Heparina/uso terapêutico , Humanos , Hiperemia/tratamento farmacológico , Mastectomia , Pessoa de Meia-Idade , Segurança do Paciente , Retalho Perfurante/transplante
13.
Dev Biol ; 418(1): 157-165, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27333774

RESUMO

Sphingosine 1-phosphate (S1P) is a bioactive lipid that acts via G protein-coupled receptors. The S1P receptor S1P1, encoded by S1pr1, is expressed in developing heart but its roles there remain largely unexplored. Analysis of S1pr1 LacZ knockin embryos revealed ß-galactosidase staining in cardiomyocytes in the septum and in the trabecular layer of hearts collected at 12.5 days post coitus (dpc) and weak staining in the inner aspect of the compact layer at 15.5 dpc and later. Nkx2-5-Cre- and Mlc2a-Cre-mediated conditional knockout of S1pr1 led to ventricular noncompaction and ventricular septal defects at 18.5 dpc and to perinatal lethality in the majority of mutants. Further analysis of Mlc2a-Cre conditional mutants revealed no gross phenotype at 12.5 dpc but absence of the normal increase in the number of cardiomyocytes and the thickness of the compact layer at 13.5 dpc and after. Consistent with relative lack of a compact layer, in situ hybridization at 13.5 dpc revealed expression of trabecular markers extending almost to the epicardium in mutants. Mutant hearts also showed decreased myofibril organization in the compact but not trabecular myocardium at 12.5 dpc. These results suggest that S1P signaling via S1P1 in cardiomyocytes plays a previously unknown and necessary role in heart development in mice.


Assuntos
Coração/embriologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Receptores de Lisoesfingolipídeo/genética , Receptores de Lisoesfingolipídeo/metabolismo , Animais , Proliferação de Células/genética , Técnicas de Inativação de Genes , Comunicação Interventricular/genética , Camundongos , Camundongos Transgênicos , Miócitos Cardíacos/citologia , Miofibrilas/genética , Miofibrilas/metabolismo , Cadeias Leves de Miosina/genética , Transdução de Sinais , Receptores de Esfingosina-1-Fosfato
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