Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
1.
Cureus ; 16(5): e60380, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38883017

RESUMEN

Introduction Managing open lower extremity fractures is challenging, with potential complications such as amputation and infection. The aim of the study was to determine whether the time delay and initial treatment of the patients treated in a non-specialized hospital before being transferred to a dedicated level I trauma center led to a worse outcome. Methods Retrospective data from 44 patients (37 males and seven females) undergoing free tissue transfer for lower extremity open fractures from January 2017 to December 2022 were analyzed. Group A received primary care externally and was later transferred for definitive treatment (n=17, 38.6%), while group B received initial care at a level I trauma center (n=27, 61.4%). Surgical outcomes, complications, the duration of the hospital stay, and assessment times were compared. Various demographic variables, co-morbidities, prior interventions, and flap types were analyzed.  Results Average age (A: 55.1±16.7; B: 38.7±19.8 years; p=0.041), overall hospitalization (A: 55.7±22.8; B: 42.8±21.3 days; p=0.041), and time to soft tissue reconstruction differed significantly between groups (A: 30.7±12.2; B: 18.9±9.3 days; p=0.013). Overall, 31.8% had multiple injuries without statistical differences between groups A and B (29.4% vs. 33.3%; p>0.05). There were no statistical differences between the groups in terms of major and minor complications and bone healing characteristics. Limb salvage was successful overall in 93.2% (A: 94.1%; B: 92.6%; P>0.05). Major complications occurred in 9.1%; three patients underwent major amputation (A: n=2; B: n=1). Minor complications were observed in 43.2% of patients (partial flap necrosis, wound dehiscence and non-union; A: 41.2%; B: 44.4%; p>0.05). Overall, 65.9% of patients (A: 64.7%; B: 66.7%; p>0.05) experienced uneventful bone healing, while 18.2% of patients (A: 23.5%; B: 14.8%; p>0.05) experienced delayed healing. Flaps used were mostly musculocutaneous (71.7%). Various assessed demographic characteristics, including age and presence of polytrauma, showed no significant influence on complications (p>0.05). Conclusion  Although there is a significant difference in the time course of externally treated patients with open fractures, prolonged treatment is not associated with a higher complication rate or compromised bone healing outcome. Despite the findings, it is important to avoid delays and strive for interdisciplinary collaboration.

2.
Wounds ; 36(5): 177-182, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38861214

RESUMEN

BACKGROUND: Full-thickness skin defects often are managed with split-thickness skin grafting. The wound healing process, including formation of new vessels during the healing of skin grafts, is complex. OBJECTIVE: To evaluate the microcirculatory changes in the treated tissue after skin grafting to analyze perfusion dynamics during the wound healing process. MATERIALS AND METHODS: Fourteen full-thickness skin defects were created on the back of 14 adult male Lewis rats. All wounds were treated with autologous split-thickness skin grafts. The perfusion dynamics were assessed for 84 days with an O2C device that combines a laser light to determine blood flow and white light to determine postcapillary SO2 and the rHb. RESULTS: Blood flow increased for 50 days after grafting. SO2 decreased in superficial skin layers (depth of 2 mm) and increased in deep skin layers (depth of 8 mm) during the entire observation period. The rHb increased until day 10 in superficial layers and until day 20 in deep tissue layers. CONCLUSION: The microcirculatory changes reflect the different phases of wound healing. Long after the skin transplants were macroscopically healed, alterations in microcirculation were still detected. These alterations were caused by the long-lasting changes in tissue metabolism due to the formation, conversion, and degradation of the dermal matrix and vessels during wound healing and scar formation.


Asunto(s)
Microcirculación , Ratas Endogámicas Lew , Trasplante de Piel , Piel , Cicatrización de Heridas , Animales , Cicatrización de Heridas/fisiología , Microcirculación/fisiología , Trasplante de Piel/métodos , Ratas , Masculino , Piel/irrigación sanguínea , Modelos Animales de Enfermedad
3.
J Reconstr Microsurg ; 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395057

RESUMEN

BACKGROUND: The versatile musculocutaneous latissimus dorsi flap and the thoracodorsal artery (TDA) perforator flap have developed into indispensable approaches in reconstructive surgery. While the anatomy of the TDA is consistent, the skin perforators vary in location and course. Dynamic infrared thermography (DIRT) recently gained popularity for perforator identification; however, its use and accuracy in thoracodorsal artery perforator (TDAP) mapping is yet to be determined. METHODS: TDAPs were visualized in 50 cases by DIRT. Based on the thermographic hotspots, the corresponding perforators were then identified by color duplex ultrasound (CDU) and handheld Doppler in a blinded fashion by two separate examiners. RESULTS: The midpoint of all perforator fascia passages was localized 99.7 mm caudal and 13.5 mm medial of the posterior axillary fold. The positive predictive value of perforator identification by dynamic infrared thermography was 86.5% and the correlating perforator fascia passage was 9.9 ± 5.8 mm from the hotspot midpoint, with a maximum of 29 mm. The positive predictive value of perforator identification by handheld Doppler was 95% and the signal was 7.2 ± 5.1 mm from the perforator fascia passage. CONCLUSION: DIRT precisely localizes TDAPs. The fusion with CDU combines both modalities' advantages. The combination with handheld Doppler is a fast way of perforator imaging, decreasing the handheld Dopplers' high false positive rate.

4.
Acta Dermatovenerol Croat ; 31(2): 64-71, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38006365

RESUMEN

BACKGROUND: This study examined the effects of irradiation with blue light on HaCaT keratinocytes. As irradiation with blue light is known to be antimicrobial, it offers a promising alternative therapy for contaminated wounds. There is evidence that red light promotes wound healing, but the potential benefits of irradiation with blue light have not yet been adequately investigated. METHODS: The rate of wound closure in sterile and contaminated cells was measured using an in vitro scratch assay wound-healing model. Additionally, cell viability after treatment was determined using a Sulforhodamine B (SRB) assay. RESULTS: In both the sterile and contaminated groups, treated cells showed delayed wound closure when compared with cells not irradiated with blue light. Additionally, treatment with blue light resulted in poorer viability in the treatment groups. CONCLUSION: Although irradiation with blue light may offer a promising alternative therapy for reducing bacterial colonization, our data indicate that re-epithelization may be negatively influenced by blue light. Further research is needed to clarify possible wound healing applications.


Asunto(s)
Queratinocitos , Terapia por Luz de Baja Intensidad , Humanos , Cicatrización de Heridas/efectos de la radiación , Luz , Terapia por Luz de Baja Intensidad/métodos
5.
Arch Orthop Trauma Surg ; 143(9): 6001-6010, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37012506

RESUMEN

INTRODUCTION: Scaphoid nonunion after failed primary treatment remains challenging particularly when entailed by bone loss, avascular necrosis or deformity. We describe a scaphoid augmentation and fixation technique for cases of recalcitrant nonunion after screw placement by autologous press fit corticocancellous dowel. This study aims to provide reliable data on clinical and radiological outcomes and to contextualize in the face of other treatment options. MATERIAL AND METHODS: The study included 16 patients with recalcitrant nonunion of the scaphoid. All patients received screw removal and scaphoid reconstruction by a dowel shaped non-vascularized corticocancellous bone graft from the iliac crest facilitating packing of the screw channel. Bone union, the scapholunate, radiolunate and intrascaphoidal angles were evaluated on X-ray and CT images, range of motion noted. Additionally grip strength, DASH and Green O'Brien scores were obtained from eight patients. RESULTS: A union rate of 73% was noted after mean follow-up of 54 months. After revisional reconstruction of the scaphoid an extension-flexion rate of 84% of the healthy side was noted while pronation-supination reached 101%. DASH score averaged at 2.9, rest pain on a numeric rating scale was 0.43 with 99% peak grip force of the healthy side. CONCLUSION: In complex cases of revisional scaphoid nonunion after screw placement, the corticocancellous iliac crest pressfit dowel is an option for augmentation and stabilization of the scaphoid by preserving the articular surface. LEVEL OF EVIDENCE: IV, retrospective case series.


Asunto(s)
Fracturas no Consolidadas , Hueso Escafoides , Humanos , Fracturas no Consolidadas/cirugía , Fracturas no Consolidadas/diagnóstico por imagen , Ilion/trasplante , Estudios Retrospectivos , Hueso Escafoides/cirugía , Radiografía , Fijación Interna de Fracturas/métodos , Trasplante Óseo/métodos , Resultado del Tratamiento
6.
Arch Orthop Trauma Surg ; 143(7): 4547-4555, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36705761

RESUMEN

INTRODUCTION: Fluctuations in the numbers of patient consultations in hand trauma emergency units are challenging in terms of both scheduling and the provision of sufficient resources. Trauma consultations in general are affected by both temporal and meteorological variables. As the genesis and epidemiology of hand trauma have their own characteristics, this study aimed to identify the influence of temporal and meteorological factors on hand trauma consultations. MATERIALS AND METHODS: All patients treated for hand trauma in our level one trauma center in 2019 were included in the study population and the data were analyzed in retrospect. The daily weather data, including temperature, sunshine duration, precipitation, humidity and wind speed, as well as temporal factors such as time of day, weekday and public holidays were considered and correlated with patient consultations. Gender differences were studied as well. RESULTS: We included 4787 hand trauma patients (66.4% male, mean age 38.4 ± 19.3 years, 31.7% occupational injuries). Significantly more consultations occurred on Saturdays as compared to weekdays (14.8 ± 0.6, n = 52 vs. 13.0 ± 0.2, n = 261; p = 0.028), and fewer occurred on official holidays (11.8 ± 0.5, n = 63 vs. 13.4 ± 0.2, n = 302; p = 0.0047). We found a significant positive correlation between daily consultations, sunshine duration (r = 0.14, p = 0.0056) and the mean temperature (r = 0.20, p < 0.0001); in contrast, a significant negative correlation between daily consultations and humidity (r = - 0.17, p = 0.001) was observed. Furthermore, fewer consultations were seen on days with precipitation (12.7 ± 0.3, n = 219 vs. 13.8 ± 0.3, n = 146; p = 0.009). The variation was considerably stronger in men. CONCLUSIONS: Hand trauma consultations increased with increasing temperatures, duration of sunshine, and decreasing humidity. Peak admissions were seen on Fridays and Saturdays. These findings can assist in predicting days with peak admissions to allocate resources appropriately.


Asunto(s)
Traumatismos de la Mano , Tiempo (Meteorología) , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Traumatismos de la Mano/epidemiología , Traumatismos de la Mano/cirugía , Hospitalización , Temperatura , Centros Traumatológicos
7.
J Reconstr Microsurg ; 39(6): 413-418, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36377126

RESUMEN

BACKGROUND: The anterolateral thigh (ALT) flap is commonly utilized in reconstructive surgery. Preoperative perforator mapping facilitates dissection. Dynamic infrared thermography can be applied to identify ALT perforators. However, its accuracy has not been evaluated in detail before. Therefore, this study aimed to assess the precision of dynamic infrared thermography in ALT perforator localization. METHODS: The survey site was defined as a 25 × 8 cm rectangle on the anterolateral thigh and a coordinate system was established. The area was examined consecutively by dynamic infrared thermography with a FLIR ONE camera after 2-minute fan precooling. Two surgeons then independently performed color duplex ultrasound on the basis of the identified hotpots. RESULTS: Twenty-four healthy subjects were examined. About 74.8% of perforators were musculocutaneous or musculoseptocutaneous. The mean distance between study area center and perforator or hotspot center was 51.8 ± 27.3 and 46.5 ± 26.2 mm, respectively. The mean distance from hotspot center to sonographic perforator fascia passage was 15.9 ± 9.9 mm with a maximum of 48.4 mm. The positive predictive value of thermographic ALT perforator identification was 93%. CONCLUSION: Thermographic hotspot and perforator location diverge widely in ALT flaps. Dynamic infrared thermography can therefore not be used as standalone technique for preoperative ALT perforator identification. However, the application before color duplex ultrasound examination is a reasonable upgrade and can visualize angiosomes and facilitate the examination.


Asunto(s)
Colgajo Perforante , Muslo , Humanos , Muslo/cirugía , Termografía/métodos , Extremidad Inferior , Fascia
8.
J Reconstr Microsurg ; 39(4): 295-300, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36150693

RESUMEN

BACKGROUND: The anterolateral thigh flap is a versatile and dependable perforator flap and is a popular choice in the reconstruction of various body sites. The variable perforator anatomy suggests preoperative perforator imaging to improve safety and speed of dissection. An innovative perforator imaging technique is thermography, which lately gained attention in plastic surgery. METHODS: Thirty-two healthy participants were included in this randomized study. One thigh was examined with dynamic infrared thermography and consecutively with ultrasound, while the contralateral thigh was examined with ultrasound as standalone technology. RESULTS: The application of dynamic infrared thermography prior to ultrasound perforator identification significantly accelerated the ultrasound examination duration by 90 to 130 seconds. The mean duplex ultrasound examination duration correlated positively with the hotspot and perforator quantity per thigh. CONCLUSION: The addition of thermographic perforator mapping can accelerate color duplex ultrasound anterolateral thigh perforator imaging. Furthermore, thermography supplements color duplex ultrasound with crucial information on angiosome location.


Asunto(s)
Colgajo Perforante , Procedimientos de Cirugía Plástica , Humanos , Termografía , Ultrasonografía Doppler en Color/métodos , Ultrasonografía Doppler Dúplex , Muslo/cirugía , Colgajo Perforante/cirugía
9.
World J Surg Oncol ; 20(1): 378, 2022 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-36464677

RESUMEN

BACKGROUND AND OBJECTIVES: Excessive preoperative blood orders frequently occur during the preoperative planning of resections of sarcomas. We aimed to develop a prediction score model that would be able to identify a patient cohort in which the cross-matching could be safely evaded. PATIENTS AND METHODS: We retrospectively analyzed data of 309 consecutive patients with extra-abdominal soft tissue sarcomas treated between September 2012 and December 2014. Scorecard scores for variables were calculated and summarized to a total score that can be used for risk stratification. The score was used in a logistic regression model. Results of the optimized model were described as a receiver operating characteristic curve. RESULTS: Preoperative units of red blood cells were requested for 206 (66.7%) patients, of which only 31 (10%) received them. Five parameters were identified with high predictive power. In the visualized barplot, there was an increased risk of blood transfusion with a higher score of TRANSAR. CONCLUSION: A TRANSAR score is a new tool that can predict the probability of transfusion for patients with sarcoma. This may reduce the number of preoperative cross-matching and blood product ordering and associated costs without compromising patient care.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Estudios Retrospectivos , Sarcoma/cirugía , Abdomen , Modelos Logísticos
10.
Microsurgery ; 42(8): 817-823, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36200703

RESUMEN

INTRODUCTION: Thorough knowledge of perforator anatomy can facilitate anterolateral thigh (ALT) free flap harvest. The selection of the right or left thigh as donor area may be supported by preoperative perforator imaging and practical considerations. The study aims to determine if the leg dominance should be taken into account, when choosing the donor thigh for ALT free flap harvest, as muscle mass and perfusion might influence perforator quantity. METHODS: ALT perforators were localized by color-coded duplex sonography and dynamic infrared thermography on both thighs within a defined 250 × 80 mm area in 24 subjects. Perforator number and thickness of subcutaneous tissue and muscle layer were compared in dominant and nondominant legs. RESULTS: We found no statistically significant difference comparing sonographically identified ALT perforator numbers and hot spot numbers in dominant and nondominant legs. Yet, we found high interindividual differences. The comparison of subcutaneous tissue and muscle thickness yielded no significant difference. CONCLUSIONS: Our study yielded no evidence for preference of the dominant or nondominant leg in ALT free flap harvesting. As we found high interindividual differences in perforator number, we suggest to rely on preoperative perforator imaging when choosing the ALT free flap donor thigh.


Asunto(s)
Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Humanos , Muslo/cirugía , Colgajo Perforante/cirugía , Pierna/cirugía , Procedimientos de Cirugía Plástica/métodos , Colgajos Tisulares Libres/cirugía
13.
Lasers Med Sci ; 37(5): 2431-2437, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35048232

RESUMEN

Phototherapy is gaining more attention in the treatment of various diseases. Especially, blue light seems to be a promising approach for wound healing promotion due to its antimicrobial and immune-modulating properties. Despite this, there is only little research focusing on the immune-modulating properties of blue light and its possible effects on wound healing. Therefore, we investigated the effects of blue light irradiation on peripheral blood mononuclear cells (PBMC) and the influence on reepithelization in vitro. PBMCs were irradiated with DermoDyne® (DermoDyne HealthCare, Berlin, Germany) and effects on cell viability, cytokine expression, and scratch wound closure were evaluated afterwards. Irradiated cells showed a higher Interleukin-γ concentration while irradiation reduced resazurin concentration in a time-dependent manner. No differences in reepithelization were detectable when keratinocytes were treated with the supernatant of these blue light irradiated PBMCs. Blue light-mediated ex vivo stimulation of PBMCs does not cause faster reepithelization in an in vitro setting. Further research is needed to investigate the wound healing effects of phototherapy with blue light.


Asunto(s)
Leucocitos Mononucleares , Cicatrización de Heridas , Queratinocitos , Luz , Fototerapia , Cicatrización de Heridas/efectos de la radiación
14.
J Reconstr Microsurg ; 38(2): 144-150, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34229351

RESUMEN

BACKGROUND: Due to the variable vascular anatomy preoperative perforator mapping facilitates anterolateral thigh (ALT) free flap harvesting. Dynamic infrared perforator imaging can assist preoperative planning by displaying hot spots that represent angiosomes. This study aims to compare previously described precooling methods to develop a standardized simplified protocol for ALT perforator planning. METHODS: Fifty thighs were examined with a FLIR ONE thermal camera. Four different cold challenges, including alcoholic disinfection, wet laparotomy sponge cooling, fan cooling, and cold pack application, were compared. Hot spot locations within a 250 mm × 80 mm area were compared double-blinded to perforator locations determined by Doppler ultrasonography considered as gold standard. RESULTS: The matching rate of thermographic hot spots and sonographically identified perforators was 34.9 ± 22.2%. An increased matching rate of 62.2 ± 42.2% was noted taking only favored perforators (septocutaneous course, diameter >1 mm, distance <3 cm to the center, and visible concomitant veins) into account. Precooling with a fan followed by alcoholic disinfection provided clearest thermograms and fastest results. CONCLUSION: Thermographic imaging is a reliable method for perforator imaging. Its supplemental use to ultrasound may reduce examination time and yield additional information. Precooling by air flow or alcoholic disinfection can be easily implemented and provide the best thermograms. The matching rate of thermographic hot spots and perforators increases when taking only clinically relevant perforators into account. Thermal perforator mapping therefore reduces distraction by negligible perforators.


Asunto(s)
Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Termografía , Muslo/cirugía
15.
Handchir Mikrochir Plast Chir ; 53(3): 323-325, 2021 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-33465786

RESUMEN

BACKGROUND: The acute calcific periarthritis is caused by hydroxyapatite deposits in the periarticular soft tissue.The symptoms resemble a pyoarthrosis, explaining high rates of misdiagnosis. PATIENTS: Presented are the cases of a 45 and a 46 years old patient, who presented with acute onset of swelling, erythema, functional impairment and pain of the hand. Periarticular calcifications were identified radiologically. RESULTS: The symptoms completely resolved in both patients within few days under conservative treatment. CONCLUSION: The acute calcific periarthritis should be considered as a differential diagnosis of pyoarthrosis in the hand, especially if no suitable trauma preceeded. Usually conservative treatment with immobilization and antiphlogistic drugs rapidly leads to a complete remission.


Asunto(s)
Calcinosis , Periartritis , Calcinosis/diagnóstico , Diagnóstico Diferencial , Durapatita , Mano , Humanos , Persona de Mediana Edad , Periartritis/diagnóstico por imagen
16.
Dermatol Surg ; 46(12): 1593-1598, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32852421

RESUMEN

BACKGROUND: Topical anesthetics are used in noninvasive transdermal anesthesia to decrease the superficial pain sensation threshold during dermatologic surgery. Combined pain relief and sensitivity loss can avoid discomfort during the surgery. OBJECTIVE: The aim of this placebo-controlled study was to compare the efficacy of 3 commonly used topical agents by collating loss of sensitivity over time. MATERIALS AND METHODS: Three topical anesthetic creams, a topical anti-inflammatory cream, and a moisturizing cream were applied on the left volar forearm of each of the 48 healthy Caucasian participants. Sensitivity was assessed with the dynamic 2-point discrimination and the Semmes-Weinstein test at 0, 60, 90, 120, 150, and 180 minutes after cream application. RESULTS: After 180 minutes, benzocaine showed a significantly lower 2-point discrimination reduction than lidocaine alone and a lidocaine and prilocaine mixture. Sensory threshold measurements by the Semmes-Weinstein test after 60 minutes revealed a significantly higher effect with lidocaine alone and with the lidocaine and prilocaine mixture than with benzocaine. CONCLUSION: The authors found a stronger skin sensitivity reduction by the eutectic lidocaine and prilocaine mixture and lidocaine alone compared with benzocaine. We suggest increased discomfort reduction in topical anesthetic supported dermatologic surgery by the eutectic mixture and lidocaine alone.


Asunto(s)
Anestesia Local/métodos , Anestésicos Locales/administración & dosificación , Procedimientos Quirúrgicos Dermatologicos/efectos adversos , Umbral del Dolor/efectos de los fármacos , Dolor Postoperatorio/prevención & control , Adolescente , Adulto , Anestésicos Combinados/administración & dosificación , Antiinflamatorios/administración & dosificación , Benzocaína/administración & dosificación , Método Doble Ciego , Femenino , Antebrazo , Voluntarios Sanos , Humanos , Combinación Lidocaína y Prilocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Nocicepción/efectos de los fármacos , Dimensión del Dolor/estadística & datos numéricos , Dolor Postoperatorio/etiología , Crema para la Piel/administración & dosificación , Resultado del Tratamiento , Adulto Joven
17.
Prog Biophys Mol Biol ; 144: 128-138, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31182191

RESUMEN

Cardiac two-pore-domain potassium (K2P) channels have been proposed as novel antiarrhythmic targets. K2P13.1 (THIK-1) channels are expressed in the human heart, and atrial K2P13.1 levels are reduced in patients with atrial fibrillation (AF) or heart failure. The first objective of this study was to investigate acute effects of antiarrhythmic drugs on human K2P13.1 currents. Second, we assessed atrial K2P13.1 remodeling in AF pigs to validate the porcine model for future translational evaluation of K2P13.1-based antiarrhythmic concepts. K2P13.1 protein expression was studied in domestic pigs during AF induced by atrial burst pacing. AF was associated with 66% reduction of K2P13.1 levels in the right atrium at 21-day follow-up. Voltage clamp electrophysiology was employed to elucidate human K2P13.1 channel pharmacology in Xenopus oocytes. Propafenone (-26%; 100 µM), mexiletine (-75%; 1.5 mM), propranolol (-38%; 200 µM), and lidocaine (-59%; 100 µM) significantly inhibited K2P13.1 currents. By contrast, K2P13.1 channels were not markedly affected by quinidine, carvedilol, metoprolol, amiodarone and verapamil. Concentration-dependent K2P13.1 blockade by mexiletine occurred rapidly with membrane depolarization and was frequency-independent. Mexiletine reduced K2P13.1 open rectification properties and shifted current-voltage relationships towards more negative potentials. In conclusion, atrial expression and AF-associated downregulation of K2P13.1 channels in a porcine model resemble human findings and support a general role for K2P13.1 in AF pathophysiology. K2P13.1 current sensitivity to antiarrhythmic drugs provides a starting point for further development of an emerging antiarrhythmic paradigm.


Asunto(s)
Antiarrítmicos/farmacología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/metabolismo , Miocardio/metabolismo , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Animales , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/genética , Fibrilación Atrial/fisiopatología , Fenómenos Electrofisiológicos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Mexiletine/farmacología , Canales de Potasio de Dominio Poro en Tándem/antagonistas & inhibidores , Canales de Potasio de Dominio Poro en Tándem/genética , Porcinos
18.
J Mol Cell Cardiol ; 126: 96-104, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30472253

RESUMEN

Two-pore-domain potassium (K2P) channels conduct background potassium currents in the heart and other tissues. K2P currents are involved in the repolarization of action potentials and stabilize the resting membrane potential. Human K2P13.1 (THIK-1) channels are expressed in the heart and have recently been implicated in atrial fibrillation. The in vivo significance of K2P13.1 currents in cardiac electrophysiology is not known. We hypothesized that Danio rerio (zebrafish) may serve as model to elucidate the functional role of cardiac K2P13.1 channels. This work was designed to characterize zebrafish orthologs of K2P13.1. Two zkcnk13 coding sequences were identified by DNA database searches and amplified from zebrafish cDNA. Human and zebrafish K2P13.1 proteins exhibit 70% (K2P13.1a) and 66% (K2P13.1b) identity. Kcnk13 expression in zebrafish was studied using polymerase chain reaction. Zebrafish kcnk13a and zkcnk13b mRNAs were detected in brain and heart. Human and zebrafish K2P13.1 currents were analyzed in the Xenopus oocyte expression system by voltage clamp electrophysiology. Zebrafish K2P13.1a polypeptides were non-functional, while zK2P13.1b channels exhibited K+ selective, outwardly rectifying currents. Zebrafish and human K2P13.1 currents were similarly activated by arachidonic acid and reduced by barium, mexiletine, lidocaine, and inhibition of phospholipase C. In conclusion, zebrafish K2P13.1b channels and their human orthologs exhibit structural and regulatory similarities. Zebrafish may be used as in vivo model for the assessment of physiology and therapeutic significance of K2P13.1.


Asunto(s)
Canales de Potasio de Dominio Poro en Tándem/genética , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Animales , Clonación Molecular , Humanos , Concentración de Iones de Hidrógeno , Péptidos/metabolismo , Canales de Potasio de Dominio Poro en Tándem/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/metabolismo
19.
Naunyn Schmiedebergs Arch Pharmacol ; 391(10): 1119-1131, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30008082

RESUMEN

K2P17.1 (TASK-4, TALK-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. Reduced K2P17.1 expression was found in atria and ventricles of heart failure (HF) patients. Modulation of K2P17.1 currents by antiarrhythmic compounds has not been comprehensively studied to date. The objective of this study was to investigate acute effects of clinically relevant antiarrhythmic drugs on human K2P17.1 channels to provide a more complete picture of K2P17.1 electropharmacology. Whole-cell patch clamp and two-electrode voltage clamp electrophysiology was employed to study human K2P17.1 channel pharmacology. K2P17.1 channels expressed in Xenopus laevis oocytes were screened for sensitivity to antiarrhythmic drugs, revealing significant activation by propafenone (+ 296%; 100 µM), quinidine (+ 58%; 100 µM), mexiletine (+ 21%; 100 µM), propranolol (+ 139%; 100 µM), and metoprolol (+ 17%; 100 µM) within 60 min. In addition, the currents were inhibited by amiodarone (- 13%; 100 µM), sotalol (- 10%; 100 µM), verapamil (- 21%; 100 µM), and ranolazine (- 8%; 100 µM). K2P17.1 channels were not significantly affected by ajmaline and carvedilol. Concentration-dependent K2P17.1 activation by propafenone was characterized in more detail. The onset of activation was fast, and current-voltage relationships were not modulated by propafenone. K2P17.1 activation was confirmed in mammalian Chinese hamster ovary cells, revealing 7.8-fold current increase by 100 µM propafenone. Human K2P17.1 channels were sensitive to multiple antiarrhythmic drugs. Differential pharmacological regulation of repolarizing K2P17.1 background K+ channels may be employed for personalized antiarrhythmic therapy.


Asunto(s)
Canales de Potasio de Dominio Poro en Tándem/fisiología , Anciano , Animales , Antiarrítmicos/farmacología , Células CHO , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Cricetulus , Femenino , Atrios Cardíacos/metabolismo , Ventrículos Cardíacos/metabolismo , Humanos , Masculino , Oocitos , Xenopus laevis
20.
Eur J Pharmacol ; 831: 94-102, 2018 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-29753045

RESUMEN

Human K2P17.1 (TASK-4, TALK-2) two-pore-domain potassium (K2P) channels have recently been implicated in heart rhythm disorders including atrial fibrillation and conduction disease. The functional in vivo significance of K2P17.1 currents in cardiac electrophysiology remains incompletely understood. Danio rerio (zebrafish) may be utilized to elucidate the role of cardiac K2P channels in vivo. The aim of this work was to identify and characterize the zebrafish ortholog of K2P17.1 in comparison to its human counterpart. The zkcnk17 coding sequence was amplified from zebrafish cDNA. Zebrafish kcnk17 mRNA expression was assessed by polymerase chain reaction. Human and zebrafish K2P17.1 currents were analyzed using two-electrode voltage clamp electrophysiology and the Xenopus oocyte expression system. Kcnk17 mRNA was detected in zebrafish brain. Human and zebrafish K2P17.1 proteins exhibited 33.4% identity. Zebrafish K2P17.1 channels conducted K+ selective currents with open rectification properties. Both human and zebrafish K2P17.1 were inhibited by barium. In contrast to human K2P17.1, zK2P17.1 currents were not sensitive to extracellular alkalization, likely due to the lack of a lysine residue involved in pH sensing of hK2P17.1. In conclusion, zebrafish and human K2P17.1 channels display similar structural and regulatory properties. Zebrafish may serve as an in vivo model to study neuronal K2P17.1 function but does not appear appropriate for cardiac electrophysiology studies. Differences in pH sensitivity of zK2P17.1 currents need to be considered when zebrafish data are extrapolated to human physiology.


Asunto(s)
Canales de Potasio de Dominio Poro en Tándem/metabolismo , Proteínas de Pez Cebra/metabolismo , Animales , Compuestos de Bario/farmacología , Femenino , Regulación de la Expresión Génica , Humanos , Concentración de Iones de Hidrógeno , Potenciales de la Membrana , Oocitos , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio de Dominio Poro en Tándem/química , Canales de Potasio de Dominio Poro en Tándem/efectos de los fármacos , Canales de Potasio de Dominio Poro en Tándem/genética , Conformación Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Relación Estructura-Actividad , Xenopus laevis/genética , Xenopus laevis/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...