Association between older subjective age and poor sleep quality: a population-based study.

OBJECTIVE: To examine the association of subjective age (SA) with sleep quality in an adult population. METHODS: In the Korean Sleep and Headache Study, 2,349 participants (49.2% men; 48.1 ± 16.4 years old) were interviewed face-to-face using structured questionnaires between September and December 2018. SA was assessed by asking participants their perceived age in years and then compared with their chronological age (CA). Participants were assigned to three groups: feeling younger, feeling their age, and feeling older. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Association between SA and sleep quality was analyzed with multiple linear regression controlling for demographics, psychosocial, and sleep characteristics. RESULTS: The group feeling older (n = 404, 17.2%; men, 58.2%; age, 46.5 ± 16.2 years) had worse sleep quality than the groups feeling younger and feeling their age (PSQI score, 4.3 ± 2.7, 3.8 ± 2.4, 3.4 ± 2.1, respectively, p <.001; prevalence of poor sleep quality, 29.0%, 18.4%, 13.5% respectively, p <.001). The association between SA and the PSQI score remained significant after adjusting for confounders (ß = 1.05, 95% confidence interval 0.26, 1.83; p <.001). Stratified analyses by sex and CA showed that the association between SA and the PSQI score was significant only in women and in middle-aged and older group (aged 50-79), suggesting that sex and CA modified the association. CONCLUSION: Age perception was associated with self-reported sleep quality, independent of CA. SA may be a useful marker that complements the conventional assessment of subjective sleep quality.

Topographic Anatomy of the Zygomatico-Orbital Artery.

ABSTRACT: The zygomatico-orbital artery (ZOA) originating from the superficial temporal artery and supplying the lower temporal region superficially has been reported. Previous studies of this artery have used definitions that are too ambiguous for the results to be directly adapted to clinical practice, including since they have resulted in marked variations in the reported incidence ofthe artery. This study dissected 193 hemifaces of 123 fixed human cadavers aged 36 to 102 years (119 males and 74 females). The authors investigated the ZOA based on the following definition: (1) it originates from the superficial temporal artery, (2) it runs mostly above the zygomatic arch, and (3) it terminates below the superior border of the orbicularis oculi muscle. The incidence of the ZOA was 22.8% (44 cases of 193 sides), and its mean diameter was 1.1 mm. The meanvertical distances from the superior borderofthe zygomatic arch to the artery were 29.6, 17.8, and 2.9 mm at the jugale, zygion, and the origin of the ZOA, respectively. An accurate definition of the ZOA and accurate knowledge of its incidence and course could be important for clinicians to avoid unintentional complications in clinical practice.

Anthropometric Analysis of the Growth Proportions of the Head and Face in Koreans.

ABSTRACT: The present study is to identify primarily the morphological characteristics in the growth proportion of the head and face for young Korean (8-24 years) and compare the magnitude of growth changes to the sex-related differences. Total 1255 were divided into 3 age groups: childhood (8-10 years), adolescence (14-16 years), and young adult (20-24 years). The anthropometric assessments were performed with 11 landmarks on the head and facial dimensions. The standardized frontal and lateral head and face photographs were analyzed the craniofacial growth proportions and morphological features for the comparison of both sexes. The noteworthy differences of anthropometric measurements between sexes with growing were noted on the lower head height (22.6%, 17.8%), midface height (22.0%, 19.6%), lower face height (23.5%, 14.7%), and face length (21.1%, 14.9%), face breadth (14.8%, 11.3%) of males and females, respectively. Whereas the upper head height (7.9%, 6.0%) and upper face height (4.2%, 0%, respectively) were less growing features. The most remarkable changes are the dimension of midface height and lower face height in both sexes. The present study could demonstrate a fundamental example to elucidate the sex-related dimensional differences for the analysis of the growth proportion of both sexes in Koreans.

Lateral branches of the facial artery and its clinical implications.

The facial artery is the main artery supplying blood to the face and is known to have facial branches of the inferior labial, superior labial, lateral nasal and angular arteries. These known major branches of facial artery run medially, however, there are sometimes branches of the facial artery heading laterally. The purpose of the present study was to investigate the lateral branches of the facial artery in face. We dissected facial branches of the facial artery in 74 cadaveric hemifaces. We investigated the presence of the lateral branches of the facial artery. Following parameters were investigated: lateral branch presence, the location of its origin, and the lateral branch diameter. Among the lateral branches, we evaluated the prevalence and diameter of the premasseteric branch. Lateral branches were observed in 48 of the 74 hemifaces (64.9%). The total number was 81 in the 48 hemifaces. The most common origin was between the inferior border of the mandible and inferior labial artery origin (42 of 81, 51.9%). The mean diameter of all lateral branches of the facial artery was 0.7 mm. Among the lateral branches, the premasseteric branches were present in 38 of 74 specimen (51.4%) and the mean diameter was 0.8 mm. The lateral branches of the facial artery may be registered in Terminologia Anatomica based on their prevalence. Accurate knowledge of the anatomy of the lateral branches of the facial artery is helpful for clinicians to avoid complications during facial procedures or maxillofacial surgeries.

Sleep structure and electroencephalographic spectral power of middle-aged or older adults: Normative values by age and sex in the Korean population.

The fine structure of sleep electrocortical activity reflects health and disease. The current study provides normative data for sleep structure and electroencephalography (EEG) spectral power measures derived from overnight polysomnography (PSG) and examines the effect of age and sex among Korean middle-aged and older adults with or without obstructive sleep apnea (OSA). We analysed home PSG data from 1,153 adult participants of an ongoing population-based cohort study, the Korean Genome and Epidemiology Study. Sleep stages were visually scored and spectral power was measured on a single-channel EEG (C4-A1). We computed spectral power for five frequency ranges. The EEG power was reported in relative (%) and log-transformed absolute values (µV2 ). With ageing, the proportion of N1 sleep increased, whereas N3 decreased, which is more noticeable in men than in women. The amount of N3 was relatively low in this cohort. With ageing, relative delta power decreased and alpha and sigma power increased for the whole sleep period, which was more pronounced during REM sleep in non-OSA. For men compared with women, relative theta power was lower during REM and sigma and beta were higher during N1 sleep. The differences of relative powers by age and sex in OSA were comparable to those in non-OSA. In a community-based Korean population, we present normative data of sleep structure and spectral power for middle-aged or older adults of a non-Caucasian ethnicity. The values varied with age and sex and were not influenced by sleep apnea.

Three-dimensional reconstruction of the luminal structure of human seminal vesicle.

The seminal vesicles are the glands of male reproductive organs that produce the fluid and nutrient constituents of semen. It has been believed for a long time that the lumen of a seminal vesicle was a single-coiled tubular structure with irregular diverticula. There are several previous reports on the symmetry, differences in morphological sizes and classification of the seminal vesicles. However, a three-dimensional-coiled tubular structure is difficult to understand using a classical anatomical methodology, and hence, three-dimensional reconstruction is needed to understand the structure of the lumen. Thirty-one seminal vesicles harvested from 21 formalin-embalmed cadavers were investigated. The seminal vesicle along with the ampulla of the ductus deferens was separated, and the length and width of each seminal vesicle were measured. The vesicles were then embedded in coloured paraffin, and the resulting paraffin block was sectioned transversely and photographed at an interval of 500 µm, with the sectioned surfaces then utilized in three-dimensional reconstruction performed by 'Reconstruct' software. The mean length and width of the seminal vesicles were 39.4 mm and 13.4 mm, respectively, and the right seminal vesicle was a little larger than the one on the left. The size differed from previous reports, while the luminal structure was similar to the classification of Aboul-azm (Archives of Andrology, 3, 1979, 287-292) but differed from that of Pereira (AJR. American Journal of Roentgenology, 69, 1953, 361-379). The seminal vesicles typically comprised about 9 curls and had about 12 diverticula. The seminal vesicles resembled a skein of coral rather than comprising a single strand. These findings will help in improving the understanding of pathophysiologies of the seminal vesicles, such as recurrent inflammation of the gland.

Femoral nerve split with variant iliacus muscle: a potential source of femoral nerve entrapment.

The iliacus muscle is a large, flat, triangle-shaped muscle located in the iliac fossa. This muscle forms part of the iliopsoas muscle complex. Although anatomical variations of iliacus muscles are rare, some variations are clinically important due to the possible coexistence of an unusual course of the femoral nerve. The femoral nerve is the largest branch of the lumbar plexus and supplies the muscles and skin in the anterior aspect of the thigh. We encountered a case of a single aberrant slip of the iliacus muscle piercing the femoral nerve in the left iliac fossa of a male cadaver aged 97 years. The potential clinical importance of this variant iliacus muscle accompanied by a femoral nerve split would be femoral neuropathy and possible consequent alterations of sensation in the anterior and medial aspects of the thigh or motor deficit of the quadriceps muscle.

Using the zygomatic arch as a reference line for clinical applications and anthropological studies.

PURPOSE: The Frankfurt line is the most frequently and widely used reference line in cephalometric analysis, but has shortcomings including the difficulty of landmark identification. This study investigated using the superior border of the zygomatic arch as a new external bony landmark, including measuring the angle between the new reference line and the Frankfurt line. METHODS: Facial computed tomography scans were obtained from 170 patients (100 males and 70 females) hospitalized at Konkuk University Chungju Hospital. After three-dimensional reconstruction, the locations of the porion and the inferior orbital rim and the superior border of the zygomatic arch were identified twice by two observers using software. A horizontal line parallel to the superior border of the zygomatic arch was established. The angle between the Frankfurt line and new reference line was then measured on each side. RESULTS: There was no significant intraobserver or interobserver bias. The angle between the Frankfurt line and the superior border of the zygomatic arch was 4.5° ± 2.5° (mean ± SD), and it was somewhat larger in females than males, but the difference was not statistically significant. CONCLUSIONS: This study demonstrated the good reproducibility of the location of the superior border of the zygomatic arch and found that the angle between the new reference line and the Frankfurt line is relatively constant. The superior border of the zygomatic arch therefore has potential as an alternative reference line to the Frankfurt line in specific clinical applications and anthropological studies, since it is a more accessible bony landmark on the external skull.

The 1,470-nm bare-fiber diode laser ablation of the great saphenous vein and small saphenous vein at 1-year follow-up using 8-12 W and a mean linear endovenous energy density of 72 J/cm.

PURPOSE: To demonstrate 1-year outcomes after low-energy endovenous laser ablation (EVLA) of incompetent saphenous veins with linear endovenous energy density (LEED) of 80 J/cm or lower with the use of a 1,470-nm diode laser. MATERIALS AND METHODS: Incompetent saphenous veins in 236 patients (355 limbs; Clinical/Etiology/Anatomy/Pathophysiology classifications of C2-C4) were treated by EVLA with a bare-tipped 1,470-nm laser with LEED no greater than 80 J/cm (mean, 72.4 J/cm) and laser power of 8-12 W. Patients were evaluated clinically and with duplex ultrasonography at 1 week and 1, 3, 6, and 12 months after EVLA to assess the technical and clinical success and complication rates. RESULTS: In the 355 limbs, the technical success rate was 100%. The great saphenous vein (GSV) remained occluded in all 229 limbs (100%) after 1 week, 202 of 203 limbs (99.5%) after 1 month, 157 of 158 limbs after 3 months (99.3%), all 99 limbs after 6 months (100%), and all 41 limbs after 1 year (100%). The small saphenous vein (SSV) remained occluded in all 103 limbs (100%) after 1 week, all 94 limbs (100%) after 1 month, 68 of 69 limbs (98.5%) after 3 months, 40 of 41 limbs (97.5%) after 6 months, and all 14 limbs after 1 year (100%). Two GSVs and two SSVs were recanalized and underwent repeated EVLA. No major complications occurred, although bruising (21% of cases), pain (15%), and paresthesia (4%) were observed. CONCLUSIONS: Low-energy EVLA with the use of a 1,470-nm laser with LEED of 80 J/cm or lower is an effective, safe, and technically successful option for the treatment of incompetent saphenous veins.

Three-dimensional linear and volumetric computed tomography analysis of the frontal sinus.

The frontal sinus is one of the four paranasal sinuses in humans, and knowledge of its anatomy is important when performing surgery involving the frontal bone or sinus. Although many studies have measured the frontal sinus using radiography and computed tomography (CT), few studies have evaluated by using three-dimensional (3D) analysis. The purpose of this study was to analyze the frontal sinus using 3D reconstruction analysis and determine the differences in linear and volumetric measurements between sexes, sides, and ages. The sample comprised 281 facial CT scans: 173 and 108 from males and females, respectively. The width, height, and length of each frontal sinus and total volume were all larger in males than in females. Almost all linear and volumetric measurements were larger in young adults than in older for both sexes, but not all of the differences were statistically significant. Linear and volumetric measurements were larger for males than females regardless of age group. There were no statistically significant differences between the right and left sides except the width in males. The size of the frontal sinus was strongly influenced by sex and age. The measurements reported here might be useful for improving surgical procedures involving the frontal sinus.

Are There Other Muscle Fibers on the Orbicularis Oris Muscle in the Upper Lip?

BACKGROUND: The elevator muscles of the upper lip are the levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor muscles, which function by means of their insertions into the skin of the upper lip. However, many textbooks and journal articles state that no muscle fibers are present on the orbicularis oris muscle in the upper lip. The authors attempted to determine whether there is a superficial muscle layer in addition to the orbicularis oris muscle in the upper lip. METHODS: The authors performed gross dissections of 10 formalin-fixed cadavers and applied micro-computed tomography to six formalin-fixed cadavers. The fine dissection of the upper lip was performed in a layer-by-layer manner that elucidated its muscle layers. The entire layer of the upper lip was separated and pretreated with phosphotungstic acid for micro-computed tomography. The samples used for micro-computed tomography were repurposed for use in histologic analysis. An ultrasonography study was also performed. RESULTS: The presence of a muscle layer on the orbicularis oris muscle was confirmed in all samples. The elevator muscle fibers of the upper lip formed a layer by combining with connective tissue. Micro-computed tomography indicated lower terminal insertions of the elevator muscles throughout the upper lip. All parts of the upper lip skin were inserted into the orbicularis oris muscle. The histologic findings were similar to those of micro-computed tomography. CONCLUSION: The authors' findings could be used to improve aesthetic and surgical procedures performed on the upper lip, such as correction of gummy smile and transverse upper labial crease, or postresection reconstruction of the upper lip.

Investigation of the Orbital Arterial Distribution Using Image Superimposition to Determine Safe Zones for Retrobulbar Injection and to Prevent Filler Complications.

BACKGROUND: Retrobulbar filler injection has recently been considered an ideal method for orbital volume enhancement due to its nontoxic, easily reversible, and noninvasive characteristics. This study determined the arterial distribution in the orbit with the aim of defining a safety zone for retrobulbar filler injections used to enhance the orbital volume. METHODS: Twenty-seven orbits of 24 formalin-embalmed cadavers were dissected. The orbital arteries were identified after removal of the eyeball, extraocular muscles, and connective tissues. The course of each orbital artery was then recorded in each specimen, and all of the courses were then superimposed to determine the arterial distribution in the orbit. RESULTS: The superimposition of lined images based on the orbital vasculature of each specimen revealed that the arterial density was highest in the superonasal region and lowest in the inferotemporal region. In particular, orbital arteries were scarce at 8 o'clock and 4 o'clock in the right and left orbits, respectively, and an artery-free zone was demonstrated in the outer part of those directions. CONCLUSIONS: When performing a transcutaneous retrobulbar injection of filler for orbital volume enhancement, the relative safety zone could be considered to be located at 8 o'clock and 4 o'clock in the right and left orbits, respectively. The detailed topographic information about the arterial distribution in the orbit, provided by the present study, may help oculofacial surgeons to avoid injury to major vessels and decrease the risk of retrobulbar hemorrhage and vision-threatening complications.

Anatomic, histologic, and ultrasound analyses of the dorsum of the hand for volumetric rejuvenation.

BACKGROUND: Volumetric rejuvenation of the dorsum of the hand with fat grafting or injectable fillers has increased in popularity in recent years. It has become widely accepted that the dorsum of the hand contains three fatty laminae: superficial, intermediate, and deep laminae. The dorsal venous plexus and dorsal cutaneous nerves are known to reside in the dorsal intermediate lamina. However, the superficial vein and cutaneous nerve might not be located in the same layer of subcutaneous tissue, as is the case in other body regions. MATERIALS AND METHODS: Eight hands were dissected in a layer-by-layer fashion from the skin to the extensor tendons. In another 13 hands from among 21 investigated cadavers, samples from the dorsum of the hand were harvested and stained using trichrome stains for histologic analysis. B-mode ultrasound was also performed for identifying structures of the dorsum of the hand. RESULTS: Anatomic dissection and histologic analysis of the dorsum of the hand revealed the presence of an unknown fascia in addition to the three known fascial layers. The additional fascia was located in the dorsal intermediate lamina and separated it into two compartments: one containing the dorsal venous plexus superficially and the other containing the dorsal cutaneous nerves deeply. Ultrasound showed corresponding structures including three hyperechoic fascial layers, three hypoechoic laminae, and additional hyperechoic fascia in dorsal intermediate lamina. CONCLUSIONS: Accurate anatomic knowledge of the dorsum of the hand will help practitioners determine the optimal and safe locations for performing fat grafting and injecting dermal fillers.

Identification of a suitable layer for injecting calcium hydroxylapatite fillers in the hands.

BACKGROUND: Hand rejuvenation has become increasingly popular in esthetic medicine. Hand rejuvenation with injectables remains challenging, and there are no established practice guidelines. The calcium hydroxylapatite (CaHA) filler injection is currently one of the most common procedures. This study aimed to identify the layer of the hand dorsum that is lifted by skin pinching and to identify the layer where an injectable filler would be placed based on the anatomical study and ultrasound findings. METHODS: The anatomic layers of the cadaveric hands were examined using the skin pinching method. Anatomic dissections and histological examinations were performed on four fixed and five fresh cadaveric hands to reveal the anatomical layers in which the CaHA filler was administered. Furthermore, 20 patients were treated with the CaHA filler, and the Doppler ultrasound was used to reveal the proper anatomical layers for filler placement. RESULTS: The study of the cadaveric hands showed that skin pinching can ensure safe entry points and can guide the cannula into safe planes without compromising the large superficial veins. A filler injection with skin pinching in cadaveric hands demonstrated that the filler was introduced primarily in the dorsal intermediate lamina where the veins are present. This was further confirmed by ultrasound findings. CONCLUSION: The dorsal intermediate lamina, which has the veins is a relatively loose structure, and the cannula was moved along this space. When the layer is stretched by skin pinching, the veins run underneath. The dorsal intermediate lamina is the appropriate layer to inject the filler.

Longitudinal detection of somatic mutations in saliva and plasma for the surveillance of oral squamous cell carcinomas.

PURPOSES: Although clinical and radiological examinations can be used to diagnose oral cancer, and surgical pathology remains the gold standard, these conventional methods have limitations. We evaluated the feasibility of longitudinal next-generation sequencing-based liquid biopsy for oral squamous cell carcinoma surveillance. MATERIALS AND METHODS: Eleven patients were enrolled, and plasma and saliva were collected before, and 1, 3, and 6 months after surgery. Tumor-specific mutations were selected using paired, whole-exome analyses of tumor tissues and whole blood. Genes frequently mutated in head and neck cancer were identified using the Cancer Genome Atlas (TCGA) and Catalogue of Somatic Mutations in Cancer (COSMIC) databases to design targeted deep sequencing panels. RESULTS: In five of the six patients with recurrent cancer, circulating tumor DNA (ctDNA) was detected earlier with liquid biopsy than with conventional monitoring techniques. Moreover, patients without recurrence exhibited decreased ctDNA allele frequency post-treatment. CONCLUSIONS: Longitudinal liquid biopsy of plasma and saliva may be feasible for detecting somatic mutations associated with oral squamous cell carcinomas. It might be attributable to determine early tumor recurrence through genetic analysis of ctDNA.

Use of the orbito-occipital line as an alternative to the Frankfort line.

Frankfort horizontal line, the line passing through the orbitale and porion, is one of the most widely used intracranial landmarks in cephalometric analysis. This study investigated the use of the orbito-occipital line extending from the orbitale to the external occipital protuberance as a novel horizontal line of the skull for substituting the Frankfort horizontal line. We evaluated the reproducibility of the new landmark and measured the angle between the orbito-occipital line and the Frankfort line. This study was conducted on 170 facial computed tomography (CT) scans of living adults from the Department of Plastic Surgery. After three-dimensionally reconstructed images were obtained from facial CT, the porion, orbitale, and external occipital protuberance were indicated by two observers twice. The angles between the orbito-meatal line (inferior orbital rim to porion; the Frankfort line) and the orbito-occipital line (inferior orbital rim to external occipital protuberance) were measured. There was no significant intraobserver or interobserver bias. The overall angle between the Frankfort line and orbito-occipital line was -0.5°±2.2° (mean±standard deviation). There was no statistically significant difference among side and sex. This study demonstrated good reproducibility of a new landmark-the external occipital protuberance-tested to replace the porion. The orbito-occipital line is a reliable, reproducible, and easily identifiable line, and has potential as a novel standard horizontal line to replace or at least supplement the Frankfort line in anthropological studies and certain clinical applications.

Location of the split line of the deep temporal fascia when reducing a zygomatic arch fracture.

BACKGROUND: The deep temporal fascia (DTF) is known to separate into two layers that descend to attach to the zygomatic arch. When surgeons reduce an isolated fracture of the zygomatic arch through a temporal approach, the temporal incision site needs to be superior to the split line of the DTF. MATERIALS AND METHODS: Sixty-seven hemifacial cadavers were investigated after removing the skin, subcutaneous tissue, and superficial temporal fascia. The superficial layer of the DTF was exposed. We cut the superficial layer along the line along, which it adhered to the deep layer inseparably. The heights of the split line of the DTF from the superior border of the zygomatic arch and from the top of the helix were measured at three points: at the jugale, zygion, and 3 cm from the tragus. RESULTS: In all cases there were thick identifiable deep layers of the DTF. The mean heights of the split line of the DTF from the superior border of the zygomatic arch were 49.8, 46.7, and 42.6 mm at the jugale, zygion, and 3 cm from the tragus, respectively; the corresponding mean heights of the split line from the top of the helix were 19.1, 15.6, and 11.4 mm. CONCLUSIONS: Knowledge of the mean height of the split line of the DTF will be helpful for surgeons to determine the temporal incision site for ensuring the safe reduction of a zygomatic arch fracture.

Morphological and Functional Evaluation of Quadricuspid Aortic Valves Using Cardiac Computed Tomography.

OBJECTIVE: The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). MATERIALS AND METHODS: We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. RESULTS: All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). CONCLUSION: Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV.

Effects of oxypeucedanin on hKv1.5 and action potential duration.

A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC(50) value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between -40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.

Direct block of cloned hKv1.5 channel by cytochalasins, actin-disrupting agents.

The action of cytochalasins, actin-disrupting agents on human Kv1.5 channel (hKv1.5) stably expressed in Ltk(-) cells was investigated using the whole cell patch-clamp technique. Cytochalasin B inhibited hKv1.5 currents rapidly and reversibly at +60 mV in a concentration-dependent manner with an IC(50) of 4.2 microM. Cytochalasin A, which has a structure very similar to cytochalasin B, inhibited hKv1.5 (IC(50) of 1.4 microM at +60 mV). Pretreatment with other actin filament disruptors cytochalasin D and cytochalasin J, and an actin filament stabilizing agent phalloidin had no effect on the cytochalasin B-induced inhibition of hKv1.5 currents. Cytochalasin B accelerated the decay rate of inactivation for the hKv1.5 currents. Cytochalasin B-induced inhibition of the hKv1.5 channels was voltage dependent with a steep increase over the voltage range of the channel's opening. However, the inhibition exhibited voltage independence over the voltage range in which channels are fully activated. Cytochalasin B produced no significant effect on the steady-state activation or inactivation curves. The rate constants for association and dissociation of cytochalasin B were 3.7 microM/s and 7.5 s(-1), respectively. Cytochalasin B produced a use-dependent inhibition of hKv1.5 current that was consistent with the slow recovery from inactivation in the presence of the drug. Cytochalasin B (10 microM) also inhibited an ultrarapid delayed rectifier K(+) current (I(K,ur)) in human atrial myocytes. These results indicate that cytochalasin B primarily blocks activated hKv1.5 channels and endogenous I(K,ur) in a cytoskeleton-independent manner as an open-channel blocker.