The acceptability, practicality, implementation and efficacy of a physical and social activity intervention 'BreatheHappy' for people with long-term respiratory conditions: A feasibility study.

OBJECTIVES: This study aimed to determine the feasibility of a group-based pilot programme of low-to-moderate physical activity training, education and social activities, by investigating acceptability, practicality, implementation and efficacy testing. We offer suggestions on programme adaptions for future study. METHODS: People with a range of chronic respiratory diseases were invited to participate in a pilot 12 week group activity programme. Activities included outdoor walking, tai-chi, education and a range of social activities. Acceptability was determined by participant experiences determined during interviews. Practicality was determined by programme and outcome measure completion, cost and adverse events. Implementation was determined according to whether the programme ran as planned. Efficacy was determined by statistical analyses of outcomes including hand grip strength, timed up and go test, COPD Helplessness Index, COPD Assessment Test, and measures of physical activity via accelerometry. RESULTS: Thematic analysis indicated that the "BreatheHappy" programme was acceptable. Seven of nine participants completed eight out of 10 sessions and the majority completed all outcome measures. "BreatheHappy" was therefore considered practical. The programme was not implemented as planned, with only 10 sessions running rather than the 12 intended. There was a significant increase in daily step counts (MD: 1284 95% CI: 240-2329 p: 0.024 effect size: 0.988), stepping time (MD: 16 min 95% CI: 5-27 min p: 0.011 effect size: 1.36) and daily minutes completing light physical activity (MD: 23 95% CI: 6-38 p: 0.006 effect size: 1.6). However, time spent sitting for ≥30 min but ≤60 min significantly increased (MD: 26 95% CI: 0.2-52 min p: 0.049 effect size: 0.931), showing signs of efficacy and changing physical activity behaviour patterns. DISCUSSION: A 10-week programme of low-moderate physical activity training, education and social activities shows signs of feasibility for future research. Suggested adaptions for future study include using physical activity measures such as daily step count or light physical activity for a primary outcome, and mental health and social health related outcome measures relatable to participant's beneficial experiences of the programme. Recruitment in future studies will try and reach both those less socially active and possibly those who have completed pulmonary rehabilitation (PR). Venues should be close to efficient transport links whilst different frequencies and durations of programme delivery should be trialled. Adequate funding should be provided for both staff running the programme and blinded research staff for outcome measurement.

The Effect of Inspiratory Muscle Training on Respiratory and Limb Locomotor Muscle Deoxygenation During Exercise with Resistive Inspiratory Loading.

We investigated how inspiratory muscle training impacted respiratory and locomotor muscle deoxygenation during submaximal exercise with resistive inspiratory loading. 16 male cyclists completed 6 weeks of either true (n=8) or sham (n=8) inspiratory muscle training. Pre- and post-training, subjects completed 3, 6-min experimental trials performed at ~80% ˙VO2peak with interventions of either moderate inspiratory loading, heavy inspiratory loading, or maximal exercise imposed in the final 3 min. Locomotor and respiratory muscle oxy-, deoxy-, and total-haemoglobin and myoglobin concentration was continuously monitored using near-infrared spectroscopy. Locomotor muscle deoxygenation changes from 80% ˙VO2peak to heavy inspiratory loading were significantly reduced pre- to post-training from 4.3±5.6 µM to 2.7±4.7 µM. Respiratory muscle deoxygenation was also significantly reduced during the heavy inspiratory loading trial (4.6±3.5 µM to 1.9±1.5 µM) post-training. There was no significant difference in oxy-, deoxy-, or total-haemoglobin and myoglobin during any of the other loading trials, from pre- to post-training, in either group. After inspiratory muscle training, highly-trained cyclists exhibited decreased locomotor and respiratory muscle deoxygenation during exercise with heavy inspiratory loading. These data suggest that inspiratory muscle training reduces oxygen extraction by the active respiratory and limb muscles, which may reflect changes in respiratory and locomotor muscle oxygen delivery.

Nanotopography and plasma treatment: redesigning the surface for vascular graft endothelialisation.

INTRODUCTION: Vascular graft materials in clinical use, such as polytetrafluoroethylene (PTFE) and Dacron, do not endothelialise and have low patency rates. The importance of an endothelial cell layer on the luminal surface of a vascular graft is well-known with surface topography and chemistry playing an important role. The aim of this study was to investigate the potential of plasma treatment and topographical structures on the luminal graft surface to enhance the self-endothelialisation potential of a nanocomposite vascular graft. METHODS: POSS-PCU is a polycarbonate urea urethane (PCU) with a nanoparticle, polyhedral oligomeric silsesquioxane (POSS) incorporated within it. Planar, microgrooved, and nanopit patterned polymer films were fabricated using photolithography, electron beam lithography, reactive ion etching, and replication by solvent casting. Films were then exposed to oxygen plasma treatment at different powers for a fixed time (40 W, 60 W, 80 W/60 seconds). Effects of plasma treatment were assessed using scanning electron microscopy, atomic force microscopy and water contact angle analysis. Human umbilical vein endothelial cell (HUVEC) proliferation and morphology were characterised using immunostaining, live/dead staining, and Coomassie blue staining. RESULTS: Successful embossing of the micro- and nanostructures was confirmed. Oxygen plasma treatment of the different samples showed that increasing power significantly increased the hydrophilicity of the samples (p < .0001). Improved HUVEC adhesion was seen on plasma modified compared with untreated samples (p < .0001). Coomassie blue staining showed that after 5 days, cells started to form monolayers and live/dead staining showed the cells were viable. Immunostaining showed that HUVECs expressed nitric oxide synthase on all topographies with focal adhesions appearing more pronounced on nanopit surfaces, showing retention of morphology and function. CONCLUSION: These encouraging results indicate a future important role for plasma treatment and nanotopography in the development of endothelialised vascular grafts.

A novel approach to controlling bacterial contamination on toothbrushes: chlorhexidine coating.

PURPOSE: This project was conducted to determine the effectiveness of chlorhexidine-coated toothbrush filaments in reducing quantities of bacteria. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved, two-group, double-blind, randomized, post-test only study was conducted. Sixty-four individuals utilized control and experimental toothbrushes, for 30 days. At the end of the study toothbrushes were returned and transported to the laboratory for analysis. Microorganisms were detached from the filaments by sonification and vortexing then plated on Mitis Salivarius (MS) (selective) and trypticase soy agar (TSA) 5% Sheep Blood (non-selective) media. Inoculated plates were incubated aerobically for 24 h at 37 degrees C. After incubation, bacterial colony-forming units (CFU) were determined. Data were analysed using Wilcoxon and Kruskal-Wallis tests. RESULTS: Fifty-nine toothbrushes were returned for analysis; experimental (n = 31) and control (n = 28). Data from TSA media revealed a mean CFU for the control group of 5.41 x 10(5) compared with 6.28 x 10(5) for the experimental group. Data from MS agar resulted in a mean CFU for the control group of 4.32 x 10(5) compared with 4.20 x 10(5) for the experimental group. CONCLUSION: Results revealed no statistically significant difference in the quantity of bacteria surviving on toothbrush filaments between control and experimental groups, on both selective and non-selective media, after 30 days.

Comparative effects of a high-intensity interval warm-up and salbutamol on the bronchoconstrictor response to exercise in asthmatic athletes.

Approximately half of all asthmatics become refractory to exercise-induced bronchoconstriction (EIB) with repeated challenges. Exercise refractoriness has been utilized by asthmatic athletes to reduce the bronchoconstrictor response to exercise prior to competition, and this has led to the observation that some asthmatic athletes can "run through" their asthma. The main aim of this study was to investigate the efficacy of short high-intensity, repeated warm-ups compared with salbutamol (a commonly used inhaled beta (2)-agonist) on the severity of EIB. Eight moderately trained (.VO(2peak), 51.9 +/- 2.3 ml . kg (-1) . min (-1)) recreational asthmatic athletes with documented EIB were tested under 4 experimental conditions: 1) control (CON) condition; 2) an interval warm-up (WU) consisting of 8 x 30-sec runs at peak treadmill speed, with 45-sec recovery between each sprint; 3) inhaling 200 microg of salbutamol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, U.K.) (IH); and 4) combining both the WU and IH session. All 4 experimental sessions were followed by an exercise challenge test (85-90 % predicted maximum heart rate for 8 min). Pulmonary function was measured pre-exercise and at 1, 5, 10, 15 min postexercise. The mean maximum percent fall in pre- to postexercise forced expiratory volume in 1-sec (FEV (1)) for all 8 asthmatic subjects during the EIB screening test (CON session) was - 18.25 +/- 4.01 %. The mean maximum percent decrease in postexercise FEV (1) significantly decreased (p < 0.05) to only - 9.1 +/- 0.6 % following the WU condition, which is below the EIB diagnostic threshold of a 10 % fall in postexercise FEV (1). The IH and WU + IH condition resulted in a substantial postexercise bronchodilation as shown by a significant increase (p < 0.05) in the mean maximum percent change in postexercise FEV (1) following the IH (+ 8.9 +/- 6.1 %) and WU + IH (+ 15.2 +/- 4.6 %) condition. Similar changes as a result of experimental condition were observed for FEF (25-75 %). These data indicate that repeated high-intensity warm-ups can lessen the bronchoconstrictor response to exercise. In addition, combining the interval warm-up with salbutamol prior to exercise resulted in substantial bronchodilation and conferred a greater protective effect against developing EIB than either intervention alone.

Cross-hybridization of closely related genes on high-density macroarrays.

DNA macroarrays are used in many areas of molecular biology research for applications ranging from gene discovery to gene expression profiling. As an increasing number of specialized macroarrays containing genes related by function or pathway are becoming available, a question that needs to be addressed is the level of hybridization signal specificity between highly similar genes that can be achieved. We have examined the ability of our LifeGrid macroarrays to distinguish hybridization signals between closely related genes. We determined the level of cross-hybridization among genes ranging from 52% to 94% sequence identity. Fragments of genes fromfive protein families were arrayed onto nylonfilters. Thefilters were subsequently hybridized with a 33P-labeled probe prepared from a pool of synthetic mRNA transcripts containing a representative of each protein family. We found that fragments containing sequences with up to 94% sequence identity displayed relatively little cross-hybridization. We conclude that this macroarray system is very specific and that hybridization signals from closely related genes can be reliably measured.

Interactions of halothane with isoproterenol and epinephrine on canine epicardial conduction velocity at normal and elevated potassium levels.

BACKGROUND: Halothane is known to potentiate catecholamine-induced depression of conduction velocity in Purkinje fibers but not endocardial muscle fibers. The purpose of this study was to examine the interactions of halothane with epinephrine and isoproterenol on canine epicardial conduction velocity at moderately elevated extracellular potassium concentration ([K]0). METHODS: Epicardial muscle strips (10x10x2 mm) were superfused with Tyrode's solution containing 4 or 8 mM [K]0 in the presence of 5 microM epinephrine or 1 microM isoproterenol with or without 0.8 mM halothane. Conduction velocity in the longitudinal and transverse directions relative to epicardial fiber orientation was recorded during alternate stimulation in each direction. RESULTS: In the presence of halothane, a change from 4 to 8 mM [K]0 decreased (P< or =0.05) longitudinal and transverse conduction velocities by 26% and 21%, respectively. Isoproterenol alone at 4 and 8 mM [K]0 depressed (P<0.05) both longitudinal and transverse conduction velocities. However, the depression of longitudinal conduction velocity by isoproterenol at 4 mM [K]0 was attenuated by halothane. Epinephrine with or without halothane depressed (P<0.05) both longitudinal and transverse conduction velocities at 8 but not at 4 mM [K]0. CONCLUSION: The results do not support a synergistic interaction between halothane and epinephrine on myocardial conduction but do demonstrate depression of conduction by epinephrine at 8 mM [K+]0, a potassium ion concentration comparable to those reported following epinephrine infusions.

Do we need another randomized controlled trial of folic acid alone?

As a public health strategy to help prevent neural tube defect-affected pregnancies, enriched flour and pasta in the United States and Canada are being fortified with folic acid, and women are being advised to take supplementary folic acid around the time of pregnancy to ensure an adequate intake. But in spite of the recently published results of a public health campaign in China, the burden of proof that folic acid alone is responsible for a decreased risk of these birth defects rests on the results of a randomized controlled trial conducted by the Medical Research Council of the United Kingdom. Supporting evidence comes primarily from studies that have shown a protective effect of multivitamins containing folic acid as one of many nutrients. Based on a striking and potentially hazardous type of non-compliance observed in an earlier study in which a participant took multiple vitamin doses simultaneously and a suggestion of similar incidents in the Medical Research Council study, we conclude that a further randomized controlled trial of the protective effect of folic acid alone may be necessary.

Multiple agents potentiate alpha1-adrenoceptor-induced conduction depression in canine cardiac purkinje fibers.

BACKGROUND: Halothane more so than isoflurane potentiates an alpha1-adrenoceptor (alpha1-AR)-mediated action of epinephrine that abnormally slows conduction in Purkinje fibers and may facilitate reentrant arrhythmias. This adverse drug interaction was further evaluated by examining conduction responses to epinephrine in combination with thiopental and propofol, which "sensitize" or reduce the dose of epinephrine required to induce arrhythmias in the heart, and with etomidate, which does not, and responses to epinephrine with verapamil, lidocaine, and l-palmitoyl carnitine, a potential ischemic metabolite. METHODS: Action potentials and conduction times were measured in vitro using two microelectrodes in groups of canine Purkinje fibers stimulated at 150 pulses/min. Conduction was evaluated each minute after exposure to 5 microm epinephrine (or phenylephrine) alone or with the test drugs. Changes in the rate of phase 0 depolarization (Vmax) and the electrotonic spread of intracellular current were measured during exposure to epinephrine with octanol to evaluate the role of inhibition of active and passive (intercellular coupling) membrane properties in the transient depression of conduction velocity. RESULTS: Lidocaine (20 microm) and octanol (0.2 mm) potentiated alpha1-AR-induced conduction depression like halothane (0.4 mm), with maximum depression at 3-5 min of agonist exposure, no decrease of Vmax, and little accentuation at a rapid (250 vs. 150 pulses/min) stimulation rate. Thiopental (95 microm), propofol (50 microm), and verapamil (2 microm) similarly potentiated epinephrine responses, whereas etomidate (10 microm) did not. Between groups, the decrease of velocity induced by epinephrine in the presence of (10 microm) l-palmitoyl carnitine (-18%) was significantly greater than that resulting from epinephrine alone (-6%; 0.05

2,4-Dichlorophenoxyacetic acid residues in semen of Ontario farmers.

Although paternal exposures to environmental toxicants probably play a role in adverse pregnancy outcomes, few data are available on the extent of this exposure. One semen and two 24-h urine samples were collected from 97 Ontario farmers who had recently used the phenoxy herbicides 2,4-D (2.4-dichlorophenoxyacetic acid) and/or MCPA ([4-chloro-2-methylphenoxyl acetic acid). Both samples were analyzed for 2,4-D using an immunoassay-based technique. Approximately 50% of the semen samples had detectable levels of 2, 4-D (> or =5.0 pph (ng/mL)). Semen levels of 2.4-D were correlated more closely with the second of the two urine samples. Although several studies have measured 2.4-D in the urine of applicators, this study is the first to attempt to measure 2,4-D levels in semen. As these pesticides can be excreted in the semen, they could be toxic to sperm cells and be transported to the woman and developing embryo/fetus. Further research is needed to understand how pesticide handling practices can affect semen pesticide residues and the relationship between the levels observed and reproductive health.

Relation of attributional beliefs to memory strategy use in children and adolescents with mental retardation.

Attributional beliefs of African American 11- and 17-year-old students with mental retardation were assessed with an open-ended interview and the Students' Perception of Control Questionnaire. Results from the questionnaire indicated that strategy ratings were intercorrelated as were capacity ratings. Yet, the constructs of strategy and capacity were differentiated by both age groups. Beliefs in the importance of internal strategies were positively related to recall and strategy use, and beliefs in the importance of external strategies were negatively related to memory strategy use and recall. Findings suggest that attributional beliefs vary among students with mental retardation and have the potential to either energize or inhibit achievement-related behavior.

The relationship of attributional beliefs to self-esteem.

Several studies have reported that beliefs about the causes of events (i.e., causal attributions) are related to achievement-oriented behavior. Skinner (1995) has suggested that achievement-oriented behavior is related to beliefs about successful strategies and beliefs about the capacity to enact those strategies. Based on Skinner's research, Wellborn, Connell, and Skinner (1989) developed the Students' Perception of Control Questionnaire (SPOCQ). In the present investigation, the SPOCQ was adapted for use with adolescents and adults. The SPOCQ and the Rosenberg Self-esteem Scale were administered to 147 college students. The internal consistency and the intercorrelations of the SPOCQ subscales were found to be acceptable. Additionally, SPOCQ scores were related to self-esteem and grade point average. There were statistically significant differences in the SPOCQ scores for males and females and in the relation of SPOCQ scores to self-esteem. It is suggested that the three constructs measured by the SPOCQ (control, strategies, and capacity) provide a more complete description of attributional beliefs than do previous scales.

Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes.

PURPOSE: Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently undergoing evaluation as an oral therapy for penile erectile dysfunction. The aims of this study were to investigate the mechanism of action of sildenafil on the neurogenic relaxation of human corpus cavernosum (HCC) in vitro and to determine the activity of sildenafil against a full range of PDE isozymes. MATERIALS AND METHODS: Strips of HCC tissue were precontracted with phenylephrine. Relaxation responses resulting from electrical field stimulation (EFS) were then determined in the presence and absence of sildenafil. The effects of sildenafil on PDE1 to 5 prepared from human tissues and PDE6 from bovine retina were determined by measuring the conversion of [3H]-cGMP or [3H]-cAMP to their respective [3H]-5'-mononucleotides. RESULTS: Sildenafil (0.001 to 1 microM) enhanced the EFS-induced, nitric oxide (NO) dependent, relaxation of HCC in a concentration-dependent manner to a maximum of 3 times the pretreatment level at 1 microM sildenafil. Compared with zaprinast, an early PDE5 inhibitor, sildenafil was approximately 240-fold more potent, inhibiting PDE5 from HCC with a geometric mean IC50 of 3.5 nM. For sildenafil, IC50 values for inhibition of PDE1 to 4 were 80 to more than 8500 times greater than that for PDE5 and the IC50 for PDE6 (33 nM) was approximately 9-fold greater. CONCLUSIONS: The data support the proposal that enhancement of penile erection by sildenafil in patients with erectile dysfunction involves potentiation of the NO-stimulated cGMP signal mediating relaxation of cavernosal smooth muscle during sexual stimulation. Sildenafil is a potent inhibitor of PDE5 from HCC, with high selectivity for PDE5 relative to other PDE isozymes.

Actions of phenylephrine, isoproterenol, and epinephrine with halothane on endocardial conduction and activation in canine left ventricular papillary muscles.

BACKGROUND: Myocardial sensitization by halothane to the arrhythmogenic effects of epinephrine involves synergistic actions mediated by alpha 1- and beta-adrenoceptors. Halothane potentiates a transient a1-adrenoceptor-mediated negative dromotropic effect of epinephrine on Purkinje fibers. This study examines how halothane alters the actions of alpha 1- and beta-agonists and epinephrine on endocardial conduction. METHODS: Superfused canine papillary muscles were mapped to locate a Purkinje-ventricular muscle junction (PVJ), and bipolar electrodes were placed to measure Purkinje and endocardial conduction velocity and PVJ conduction time during stimulation of the Purkinje layer. The effects of exposure to 5 microM phenylephrine, 1 microM isoproterenol, or 5 microM epinephrine on conduction were determined in the absence and presence of 0.4 mM halothane in three groups of 10 preparations. RESULTS: Isoproterenol slightly increased Purkinje conduction velocity and markedly improved conduction at the PVJ and in the endocardium similarly in the presence or absence of halothane. Phenylephrine depressed Purkinje velocity (-12%) only in the presence of halothane and did not slow conduction at the PVJ or in the myocardium. Epinephrine transiently depressed Purkinje velocity, more so with (-22%) than without (-12%) halothane (P < or = 0.01), and simultaneously facilitated conduction at the PVJ and in the myocardium. CONCLUSIONS: The prodysrhythmic actions of epinephrine with halothane may involve disparate effects on conduction, including speeding on conduction at the PVJ and in the myocardium, similar to that produced by isoproterenol, accompanied by simultaneous but transient alpha 1-mediated depression of conduction in the Purkinje system.

Effect of thoracic epidural anesthesia on spontaneous postinfarction ventricular dysrhythmia in awake dogs.

BACKGROUND AND OBJECTIVES: Sympathetic neural activity contributes to the genesis of ventricular ectopic activity, particularly in the setting of myocardial ischemia and infarction, so thoracic epidural anesthesia should diminish ventricular ectopy by blocking sympathetic innervation of the heart. However, the possible antidysrhythmic effect of epidural anesthesia has been studied only in the presence of general anesthesia. We therefore examined changes in spontaneous postinfarction ventricular dysrhythmia during thoracic epidural anesthesia in awake dogs. METHODS: A survivable myocardial infarction was created by two-stage ligation of the left anterior descending coronary artery. The following day, multifocal idioventricular tachycardia was the predominant cardiac rhythm. Lidocaine was administered either by thoracic epidural catheter to achieve block of at least the first five thoracic segments or intravenously as a control for direct effects, without concurrent general anesthesia or sedation. Electrocardiographic recordings were analyzed for the number of ventricular ectopic and sinoatrial depolarizations. RESULTS: Epidural and intravenous administration both produced plasma lidocaine concentrations of about 2 mg/mL. There was no change in rhythm following intravenous lidocaine. During epidural anesthesia, total ectopic beats per minute decreased from 167 +/- 8 to 135 +/- 14 (mean +/- SE, P < .05), and the dysrhythmic ratio (ventricular beats/total beats) decreased from 0.93 +/- 0.03 to 0.81 +/- 0.08 (P < .05). However, ventricular tachydysrhythmia remained the predominant rhythm. CONCLUSIONS: Epidural block modestly reduces spontaneous ventricular dysrhythmia in a perioperative setting in dogs following a large myocardial infarction. These findings do not support the choice of thoracic epidural anesthesia for the purpose of preventing or decreasing severe ventricular dysrhythmia.

Voltage-dependent effects of volatile anesthetics on cardiac sodium current.

Cardiac dysrhythmias during inhaled anesthesia are well documented and may, in part, involve depression of the fast inward Na+ current (INa) during the action potential upstroke. In this study, we examined the effects of halothane, isoflurane, and sevoflurane at clinically relevant concentrations on INa in single ventricular myocytes isolated enzymatically from adult guinea pig hearts. INa was recorded using standard whole-cell configuration of the patch clamp technique. Halothane at 0.6 mM and 1.2 mM produced significant (P < 0.05) depressions of peak INa of 12.3% +/- 1.8% and 24.4% +/- 4.1% (mean +/- SEM, n = 12), respectively. Isoflurane (0.5 mM, n = 12; 1.0 mM, n = 15) and sevoflurane (0.6 mM, n = 14; 1.2 mM, n = 12) were less potent than halothane, decreasing peak INa by 4.8% +/- 1.1% and 11.4% +/- 1.4% (isoflurane) and 3.0% +/- 0.7% and 10.7% +/- 3.9% (sevoflurane). The depressant effects on INa were reversible in all cases. For all anesthetics tested, the degree of block increased at more depolarizing potentials. Anesthetics induced significant shifts in the steady-state inactivation and activation of the channel toward more hyperpolarizing potentials. The present findings indicate that volatile anesthetics at clinical concentrations decrease the cardiac INa in a dose- and voltage-dependent manner. At approximately equianesthetic concentrations, the decrease of INa caused by halothane was twice that observed with isoflurane or sevoflurane.

Modulation of cardiac sodium current by alpha1-stimulation and volatile anesthetics.

BACKGROUND: Alpha1-adrenoceptor stimulation is known to produce electrophysiologic changes in cardiac tissues, which may involve modulations of the fast inward Na+ current (I(Na)). A direct prodysrhythmic alpha1-mediated interaction between catecholamines and halothane has been demonstrated, supporting the hypothesis that generation of halothane-epinephrine dysrhythmias may involve slowed conduction, leading to reentry. In this study, we examined the effects of a selective alpha1-adrenergic receptor agonist, methoxamine, on cardiac I(Na) in the absence and presence of equianesthetic concentrations of halothane and isoflurane in single ventricular myocytes from adult guinea pig hearts. METHODS: I(Na) was recorded using the standard whole-cell configuration of the patch-clamp technique. Voltage clamp protocols initiated from two different holding potentials (V(H)) were applied to examine state-dependent effects of methoxamine in the presence of anesthetics. Steady state activation and inactivation and recovery from inactivation were characterized using standard protocols. RESULTS: Methoxamine decreased I(Na) in a concentration- and voltage-dependent manner, being more potent at the depolarized V(H). Halothane and isoflurane interacted synergistically with methoxamine to suppress I(Na) near the physiologic cardiac resting potential of -80 mV. The effect of methoxamine with anesthetics appeared to be additive when using a V(H) of -110 mV, a potential where no Na+ channels are in the inactivated state. Methoxamine in the absence and presence of anesthetics significantly shifted the half maximal inactivation voltage in the hyperpolarizing direction but had no effect on steady-state activation. CONCLUSION: The present results show that methoxamine (alpha1-adrenergic stimulation) decreases cardiac Na+ current in a concentration- and voltage-dependent manner. Further, a form of synergistic interaction between methoxamine and inhalational anesthetics, halothane and isoflurane, was observed. This interaction appears to depend on the fraction of Na+ channels in the inactivated state. (Key words: Anesthetics, volatile: halothane; isoflurane; methoxamine. Patch clamp: whole-cell configuration; sodium current; ventricular guinea pig myocytes.)

Epinephrine dysrhythmogenicity is not enhanced by subtoxic bupivacaine in dogs.

Since bupivacaine and epinephrine may both precipitate dysrhythmias, circulating bupivacaine during regional anesthesia could potentiate dysrhythmogenic effects of epinephrine. We therefore examined whether bupivacaine alters the dysrhythmogenicity of subsequent administration of epinephrine in conscious, healthy dogs and in anesthetized dogs with myocardial infarction. Forty-one conscious dogs received 10 micrograms.kg-1.min-1 epinephrine. Seventeen animals responded with ventricular tachycardia (VT) within 3 min. After 3 h, these responders randomly received 1 or 2 mg/kg bupivacaine or saline over 5 min, followed by 10 micrograms.kg-1.min-1 epinephrine. In the bupivacaine groups, epinephrine caused fewer prodysrhythmic effects than without bupivacaine. VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micrograms.kg-1.min-1 epinephrine until VT appeared. After 45 min, 1 mg/kg bupivacaine was injected over 5 min, again followed by 4 micrograms.kg-1.min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine.

Influence of intelligence on memory development.

The development of memory strategy use in children with and without mental retardation was investigated. Strategy use, recall, metamemory, and attributional beliefs were assessed over a 3-year period beginning at 10 years of age. Although both groups employed effective strategies and increased their use of these strategies across years, students without mental retardation were more strategic. Although strategy use was a significant predictor of recall for both groups, attributional beliefs and metamemory predicted recall only for the students without retardation in Years 2 and 3, respectively. Slight differences emerged as a function of intelligence in the types of strategies used as well as the ways in which strategy knowledge and beliefs were associated with memory performance.