We have investigated the physiological role of the "rapidly activating" delayed rectifier K+ current (IKr) in pacemaker activity in isolated sinoatrial node (SAN) myocytes and the expression of mouse ether-a-go-go (mERG) genes in the adult mouse SAN. In isolated, voltage-clamped SAN cells, outward currents evoked by depolarizing steps (greater than -40 mV) were strongly inhibited by the class III methanesulfonanilide compound E-4031 (1-2.5 microM), and the deactivation "tail" currents that occurred during repolarization to a membrane potential of -45 mV were completely blocked. E-4031-sensitive currents (IKr) reached a maximum at a membrane potential of -10 mV and showed pronounced inward rectification at more-positive membrane potentials. Activation of IKr occurred at -40 to 0 mV, with half-activation at about -24 mV. The contribution of IKr to action potential repolarization and diastolic depolarization was estimated by determining the E-4031-sensitive current evoked during voltage clamp with a simulated mouse SAN action potential. IKr reached its peak value (approximately 0.6 pA/pF) near -25 mV, close to the midpoint of the repolarization phase of the simulated action potential, and deactivated almost completely during the diastolic interval. E-4031 (1 microM) slowed the spontaneous pacing rate of Langendorff-perfused, isolated adult mouse hearts by an average of 36.5% (n = 5). Expression of mRNA corresponding to three isoforms coded by the mouse ERG1 gene (mERG1), mERG1a, mERG1a', and mERG1b, was consistently found in the SAN. Our data provide the first detailed characterization of IKr in adult mouse SAN cells, demonstrate that this current plays an important role in pacemaker activity, and indicate that multiple isoforms of mERG1 can contribute to native SAN IKr.
The induction of mild hypothermia attenuates cardiac and respiratory dysfunction and counteracts sympathetic activation during experimental endotoxemia. This was not associated with lower plasma cytokine levels, indicating a reduction of cytokine responsiveness by mild hypothermia.
BackgroundIn an emergency room of internal medicine, triage and treatment of patients deserve first priority. However, biopsychosocial case complexity may also affect patient health outcome but has not yet been explored in this setting. Therefore, the aims of the study are (1) to estimate prevalence rates of complex patients in the emergency room (ER), (2) to describe biopsychosocial complexity in this population and (3) to evaluate possible correlations between patient profiles regarding case complexity and further clinical treatment.MethodsDuring a study period of one week, all patients of an emergency room of internal medicine who were triaged to Manchester levels three to five were invited to participate in the study. Biopsychosocial case complexity was assessed by the INTERMED method. Psychosocial interventions were evaluated based on all documented interventions and recommendations given at the emergency room and during inpatient treatment.ResultsStudy participants consisted of 167 patients with a subgroup of 19% (n = 32) receiving subsequent inpatient-treatment at the department. High biopsychosocial case complexity was found in 12% (n = 20) of the total sample (INTERMED score >20). This finding was paralleled by a cluster analysis suggesting three clusters with one highly complex patient group of 14%. These highly complex patients differed significantly from the other clusters as they had visited the emergency room more often within the last year and lived alone more frequently. In addition, admission rates were highest in this group. During ER treatment and subsequent inpatient treatment, 21% of highly complex patients received interventions addressing psychosocial factors as compared to 6% and 7%, respectively, in the other clusters.ConclusionsA standardized screening of biopsychosocial case complexity among ‘frequent utilizers’ of the ER would be helpful to detect specific multidisciplinary health care needs among this particularly burdened patient group.
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