Background/Aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current ITASK-1. Methods and Results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (ITASK-1) in human atrial tissue. We show that ITASK-1 contributes to the sustained outward current IKsus and that ITASK-1 is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of ITASK-1 can alter human atrial action potential duration. Conclusion: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation.
Volatile anesthetics have been shown to activate various two-pore (2P) domain K(+) (K(2P)) channels such as TASK-1 and TREK-1 (TWIK-related acid-sensitive K(+) channel), and mice deficient in these channels are resistant to halothane-induced anesthesia. Here, we investigated whether K(2P) channels were also potentially important targets of intravenous anesthetics. Whole cell patch-clamp techniques were used to determine the effects of the commonly used intravenous anesthetics etomidate and propofol on the acid-sensitive K(+) current in rat ventricular myocytes (which strongly express TASK-1) and selected human K(2P) channels expressed in Xenopus laevis oocytes. In myocytes, etomidate decreased both inward rectifier K(+) (K(ir)) current (I(K1)) and acid-sensitive outward K(+) current at positive potentials, suggesting that this drug may inhibit TASK channels. Indeed, in addition to inhibiting guinea pig Kir2.1 expressed in oocytes, etomidate inhibited human TASK-1 (and TASK-3) in a concentration-dependent fashion. Propofol had no effect on human TASK-1 (or TASK-3) expressed in oocytes. Moreover, we showed that, similar to the known effect of halothane, sevoflurane and the purified R-(-)- and S-(+)-enantiomers of isoflurane, without stereoselectivity, activated human TASK-1. We conclude that intravenous and volatile anesthetics have dissimilar effects on K(2P) channels. Human TASK-1 (and TASK-3) are insensitive to propofol but are inhibited by supraclinical concentrations of etomidate. In contrast, stimulatory effects of sevoflurane and enantiomeric isoflurane on human TASK-1 can be observed at clinically relevant concentrations.
Objectives: Standard therapy in Germany for acute whiplash injury has traditionally included a soft collar (cervical orthosis), an approach that is passive compared with early exercise and mobilisation. The purpose of this study is to examine the recovery in the first six weeks of groups of acute whiplash injury patients subjected to two different treatment approaches, the traditional approach of a collar compared with active, early mobilisation. Methods: Between August 1997 and February 2000 a randomised clinical trial with a total of 200 patients was performed. A total of 97 were randomly assigned to a collar therapy group, and 103 to the exercise group, treated by a physiotherapist. Study participants recorded average pain and disability twice (baseline and six week follow up) during a one week period by diary, using numeric visual analogue (VAS) rating scales ranging from 0 to 10. Results: The initial mean VAS pain intensity and VAS disability reported by the collar therapy group and the exercise group showed no statistical difference. The mean VAS pain rating reported by the collar therapy group after six weeks was 1.60 and mean VAS disability rating was 1.56. The mean VAS pain intensity of the exercise group was 1.04 and mean VAS disability was 0.92. These differences between the groups were both significant, as was the reduction in the prevalence of symptoms in the exercise therapy group compared with the collar group at six weeks. Conclusions: Early exercise therapy is superior to the collar therapy in reducing pain intensity and disability for whiplash injury.
Spinal anaesthesia with 50 mg of plain 1% 2-chloroprocaine is similar to 10 mg of plain 0.5% bupivacaine in terms of onset of sensory block at T10 but shows quicker recovery from anaesthesia than with 0.5% bupivacaine.
The severity of nerve injury after needle nerve perforation was related to the diameter of the applied cannula. However, no such difference exists for regional inflammation. Functional consequences of these findings need to be determined. Currently, small-diameter cannulae may be advisable for peripheral nerve blocks to minimize the risk of nerve injury in the case of nerve perforation.
Background: Septic shock is a leading cause of acute kidney injury (AKI). Endotoxins and cytokine levels are associated with the occurrence and severity of AKI, and different blood purification devices are available to remove them from circulation. One such device, oXiris, is a hollow-fibre purification filter that clears both endotoxins and cytokines. Due to limited evidence, clinical use of this device is not currently advocated in guidelines. However, clinics do regularly use this device, and there is a critical need for guidance on the application of it in sepsis with and without AKI. Method: A modified Delphi-based method was used to collate European experts’ views on the indication(s), initiation and discontinuation criteria and success measures for oXiris. Results: A panel of 14 participants was selected based on known clinical expertise in the areas of critical care and sepsis management, as well as their experience of using the oXiris blood purification device. The participants used different criteria to initiate treatment with oXiris in sepsis patients with and without AKI. Septic shock with AKI was the priority patient population, with oXiris used to rapidly improve haemodynamic parameters. Achieving haemodynamic stability within 72 h was a key factor for determining treatment success. Conclusion: In the absence of established guidelines, users of hollow-fibre purification devices such as oXiris may benefit from standardised approaches to selecting patients and initiating and terminating treatment, as well as measuring success. Further evidence in the form of randomised clinical trials is urgently required.
The aim of this study was to compare the effect of a physical therapy regimen including active exercises with the current standard treatment on reduction of pain 6 weeks and 6 months after whiplash injury caused by motor vehicle collision. Two hundred patients were enrolled in a prospective randomized controlled trial. In the standard group, treatment consisted of immobilization with a soft collar over 7 days. In the physical therapy group, patients were scheduled for 10 physical therapy appointments including active exercises within 14 days after enrollment. Pain intensity was rated by all patients daily during the first week, the sixth week, and 6 months after recruitment, using a numeric rating scale (0-10). Data analyses were performed by comparing the mean (over 1 week) pain scores between the two different treatment groups. Ninety-seven patients were randomly assigned to the standard treatment group and 103 to the physical therapy group. During the first week, there was no significant difference in mean pain intensity between the standard treatment group (4.76+/-2.15) and the physical therapy group (4.36+/-2.14). However, after 6 weeks, mean pain intensity was significantly (p=0.002) lower in the physical therapy group (1.49+/-2.26 versus 2.7+/-2.78). Similarly, after 6 months, significantly (p<0.001) less pain was reported in the physical therapy group (1.17+/-2.13) than the standard treatment group (2.33+/-2.56). We conclude that a physical therapy regimen which includes active exercises is superior in reducing pain 6 weeks and 6 months after whiplash injury compared to the current standard treatment with a soft collar.
The confidence interval for differences suggests minimal current intensity to elicit a motor response that cannot reliably discern between a needle-nerve contact from intraneural needle placement. In addition, an EMR at threshold currents <0.2 mA (irrespective of the applied pulse duration) indicates intraneural needle placement or needle-nerve contact.
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