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Tedisamil and lidocaine enhance each other's antiarrhythmic activity against ischaemia-induced arrhythmias in rats.

ABSTRACT: 1. Combinations of the action potential-widening drug tedisamil (Class III antiarrhythmic activity), and the inactivated state sodium channel blocker lidocaine (Class Ib antiarrhythmic activity) were assessed for antiarrhythmic actions in a rat model of ischaemia-induced arrhythmias and for electrophysiological actions in normal rat myocardial tissue. 2. Both tedisamil and lidocaine dose-dependently suppressed ischaemia-induced arrhythmias. The ED(50) values were 3.0+/-1.3 and 4.9+/-0.6 micro mol kg(-1) min(-1), respectively. 3. Combinations of the two drugs acted synergistically such that the ED(50) for tedisamil was reduced to 0.8+/-0.2 micro mol kg(-1) min(-1) in the presence of 2 micro mol kg(-1) min(-1) lidocaine. Similarly, the ED(50) for lidocaine was reduced to 0.7+/-0.2 micro mol kg(-1) min(-1) in the presence of 2 micro mol kg(-1) min(-1) tedisamil (both P<0.05). 4. In a separate series of experiments in which normal ventricular tissue was electrically stimulated, 2 micro mol kg(-1) min(-1) lidocaine produced a leftward shift in the dose-response curve for tedisamil's effect on effective refractory period (P<0.05). This dose of lidocaine had no effect on its own. These data indicate that the synergistic actions of combinations of tedisamil and lidocaine were mediated, at least in part, by extension of effective refractory period in normal myocardial tissue. 5. In contrast to the strategy of developing drugs that are selective for a single electrophysiological mechanism, the results of the present study suggest that effective antiarrhythmic drugs might be developed by optimising the combination of two complimentary electrophysiological mechanisms (i.e., action potential-prolonging activity and inactivated state sodium channel blockade).

SUBMITTER: Sarraf G

PROVIDER: S-EPMC1573972 | biostudies-other | 2003 Aug

REPOSITORIES: biostudies-other

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Project description:BackgroundPhysical activity patterns have been shown to change significantly across the transition to retirement. As most older adults approach retirement as part of a couple, a better understanding of how spousal pairs influence each other's physical activity behaviour in retirement may help inform more effective interventions to promote physical activity in older age. This qualitative study aimed to explore and describe how couples influence each other's physical activity behaviour in retirement.MethodsA qualitative descriptive study that used purposive sampling to recruit seven spousal pairs with at least one partner of each pair recruited from the existing EPIC-Norfolk study cohort in the east of England, aged between 63 and 70 years and recently retired (within 2-6 years). Semi-structured interviews with couples were performed, audio-recorded, transcribed verbatim and analysed using data-driven content analysis.ResultsThree themes emerged: spousal attitude towards physical activity, spouses' physical activity behaviour and spousal support. While spouses' attitudes towards an active retirement were concordant, attitudes towards regular exercise diverged, were acquired across the life course and were not altered in the transition to retirement. Shared participation in physical activity was rare and regular exercise was largely an individual and independent habit. Spousal support was perceived as important for initiation and maintenance of regular exercise.ConclusionsInterventions should aim to create supportive spousal environments for physical activity in which spouses encourage each other to pursue their preferred forms of physical activity; should address gender-specific needs and preferences, such as chances for socialising and relaxation for women and opportunities for personal challenges for men; and rather than solely focusing on promoting structured exercise, should also encourage everyday physical activity such as walking for transport.

Project description:Introduction:The incidence of acute pancreatitis (AP) and the prevalence of metabolic syndrome (MetS) are growing worldwide. Several studies have confirmed that obesity (OB), hyperlipidemia (HL), or diabetes mellitus (DM) can increase severity, mortality, and complications in AP. However, there is no comprehensive information on the independent or joint effect of MetS components on the outcome of AP. Our aims were (1) to understand whether the components of MetS have an independent effect on the outcome of AP and (2) to examine the joint effect of their combinations. Methods:From 2012 to 2017, 1435 AP cases from 28 centers were included in the prospective AP Registry. Patient groups were formed retrospectively based on the presence of OB, HL, DM, and hypertension (HT). The primary endpoints were mortality, severity, complications of AP, and length of hospital stay. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Results:1257 patients (55.7 ± 17.0 years) were included in the analysis. The presence of OB was an independent predictive factor for renal failure [OR: 2.98 (CI: 1.33-6.66)] and obese patients spent a longer time in hospital compared to non-obese patients (12.1 vs. 10.4 days, p = 0.008). HT increased the risk of severe AP [OR: 3.41 (CI: 1.39-8.37)], renal failure [OR: 7.46 (CI: 1.61-34.49)], and the length of hospitalization (11.8 vs. 10.5 days, p = 0.020). HL increased the risk of local complications [OR: 1.51 (CI: 1.10-2.07)], renal failure [OR: 6.4 (CI: 1.93-21.17)], and the incidence of newly diagnosed DM [OR: 2.55 (CI: 1.26-5.19)]. No relation was found between the presence of DM and the outcome of AP. 906 cases (mean age ± SD: 56.9 ± 16.7 years) had data on all four components of MetS available. The presence of two, three, or four MetS factors increased the incidence of an unfavorable outcome compared to patients with no MetS factors. Conclusion:OB, HT, and HL are independent risk factors for a number of complications. HT is an independent risk factor for severity as well. Components of MetS strongly synergize each other's detrimental effect. It is important to search for and follow up on the components of MetS in AP.

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Tedisamil and lidocaine enhance each other's antiarrhythmic activity against ischaemia-induced arrhythmias in rats.

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