The acid-sensitive potassium channel TASK-1 in rat cardiac muscle.

OBJECTIVE: The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I(TASK)) and its inhibition via alpha1-adrenergic receptors was studied in rat ventricular cardiomyocytes. METHODS: Quantitative RT-PCR experiments were carried out with mRNA from rat heart. Patch-clamp recordings were performed in isolated rat cardiomyocytes. TASK-1 and other K+ channels were expressed in Xenopus oocytes to study the pharmacological properties of a new TASK-1 channel blocker, A293. RESULTS: TASK-1 channels were found to be strongly expressed in rat heart. Analysis of the sensitivity of various K+ channels to A293 in Xenopus oocytes showed that at low concentrations A293 was a selective blocker of TASK-1 channels. I(TASK) in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of approximately 0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD(50)) by 31+/-3% at a stimulation rate of 4 Hz. The plausibility of the effects of A293 on APD50 was checked with a mathematical action potential model. Application of the alpha1-adrenergic agonist methoxamine inhibited I(TASK) in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I(TASK). This effect was abolished in the presence of the alpha1A-antagonist 5-methyl-urapidil. CONCLUSIONS: Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors.

Physical therapy and active exercises--an adequate treatment for prevention of late whiplash syndrome? Randomized controlled trial in 200 patients.

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 stretch-activated potassium channel TREK-1 in rat cardiac ventricular muscle.

OBJECTIVE: The biophysical properties and the regulation of the two-pore-domain potassium channel TREK-1 were studied in rat cardiomyocytes. METHODS: RT-PCR, immunohistochemistry and patch-clamp recording were performed in isolated rat ventricular cardiomyocytes. In some whole-cell-clamp experiments the myocytes were mechanically stretched using a glass stylus. RESULTS: We found strong expression of a splice variant of TREK-1 in rat heart. Immunohistochemistry with antibodies against TREK-1 showed localization of the channel in longitudinal stripes at the external surface membrane of cardiomyocytes. When the cardiomyocytes were mechanically stretched, an outwardly rectifying K+ current component could be detected in whole-cell recordings. In single-channel recordings with symmetrical high K+ solution, two TREK-like channels with 'flickery-burst' kinetics were found: a 'large conductance' K+ channel (132+/-5 pS at positive potentials) and a novel 'low-conductance' channel (41+/-5 pS at positive potentials). The low-conductance channel could be activated by negative pressure in inside-out patches, positive pressure in outside-out patches, intracellular acidification and application of arachidonic acid. Its open probability was strongly increased by depolarization, due to decreased duration of gaps between bursts. The biophysical properties of the two cardiac TREK-like channels were similar to those of TREK-1 channels expressed in HEK293 cells, which both displayed low- and high-conductance modes. CONCLUSIONS: Our results suggest that the two TREK-like channels found in rat cardiomyocytes may reflect two different operating modes of TREK-1. The novel low-conductance channels described here may represent the major operating mode of TREK-1. The current flowing through mechanogated TREK-1 channels may serve to counterbalance the inward current flowing through stretch-activated non-selective cation channels during the filling phase of the cardiac cycle and thus to prevent the occurrence of ventricular extrasystoles.

The reliability and validity of the upper lip bite test compared with the Mallampati classification to predict difficult laryngoscopy: an external prospective evaluation.

Recently, a new bedside screening test to predict the occurrence of a difficult laryngoscopy has been developed as a substitute for the Mallampati classification. The Upper-Lip-Bite test (ULBT) evaluated the patient's ability to reach or completely cover the upper lip with the lower incisors. It is often accepted that new predictive tools should undergo an external evaluation before the tool is used in clinical practice. Thus, we evaluated this test with respect to applicability, interobserver reliability, and discriminating power and compared it with the Mallampati-score (using Samsoon and Young's modification). The ULBT could not be applied in 12% of all patients (Mallampati score, <1%). However, the interobserver reliability was better for the ULBT (kappa = 0.79 versus kappa = 0.59). The discriminating power to predict a patient with difficult laryngoscopy was evaluated in 1425 consecutive patients. Both tests were assessed simultaneously in these patients by two specially trained independent observers. After the induction of anesthesia, the laryngoscopic view was assessed by the attending anesthesiologist using the classification of Cormack and Lehane. A grade I or II was called easy laryngoscopy and grade III and IV difficult laryngoscopy. The discriminating power for both tests was low (0.60 for the ULBT [95% confidence interval, 0.57-0.63] and 0.66 [0.63-0.69]) for the Mallampati score), indicating that both tests are poor predictors as single screening tests.

Cost analyses of remifentanil, mivacurium and ropivacaine - a systematic review.

Remifentanil, mivacurium and ropivacaine are the latest innovations in clinical anaesthesia and have gained increasing importance in daily practise due to their unique pharmacodynamic and pharmacokinetic properties. However, drug acquisition costs for these agents are considerably higher in most countries than for comparable substances. This review provides a systematic, critical appraisal of pharmacoeconomic studies with remifentanil, mivacurium and ropivacaine, primarily based on prospective, randomised trials. Results from analyses using cost-minimising techniques stress the issue of the higher drug acquisition costs. However, studies using a more sophisticated method (e.g., cost-effectiveness analysis) indicate comparable costs or even financial advantage in favour of the newer investigative drugs remifentanil, mivacurium and ropivacaine.