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Cardiac events in patients with negative maximal versus negative submaximal dobutamine echocardiograms undergoing noncardiac surgery: importance of resting wall motion abnormalities.

OBJECTIVES: This study sought to evaluate the negative predictive value (NPV) of preoperative dobutamine stress echocardiography (DSE) in patients who fail to achieve target heart rate (HR) and assess the influence of resting wall motion abnormalities (WMAs) without demonstrable ischemia on perioperative events. BACKGROUND: The prognostic value of a negative-submaximal DSE study before noncardiac surgery is unknown. METHODS: Consecutive patients (n = 429) who underwent surgery over a three-year period, preceded by DSE, were included. We compared perioperative event rates among those without inducible ischemia according to whether or not 85% age-adjusted maximum HR was achieved, and whether WMAs were present at rest. RESULTS: Of 397 negative DSEs, peak HR was <85% maximum predicted in 62 (16%). Most were receiving beta-blockers (77%). The average dobutamine and atropine doses were 48 microg/kg/min and 1.2 mg, respectively. Average HR was 115 beats/min (74% maximum predicted). Perioperative myocardial infarctions occurred more frequently in patients with positive tests (3 of 32 [9.4%] vs. 7 of 397 [1.8%]; p = 0.03), but with similar frequency among the negative-maximal and negative-submaximal groups (6 of 335, 1.8% vs. 1 of 62, 1.6%, respectively). Accordingly, the NPV was 98% in both subgroups. Events occurred exclusively in patients with WMAs at rest: 7 of 100 (7%) versus 0 of 297 (0%) (p < 0.0001). CONCLUSIONS: In patients undergoing preoperative DSE, failure to achieve target HR is not uncommon despite an aggressive DSE regimen. A negative DSE without resting WMAs has excellent NPV regardless of the HR achieved. Patients with resting WMAs appear to be at increased risk for perioperative events even without provokable ischemia.

Adrenergic beta-Agonists↗

Development of a culture system that supports adult microglial cell proliferation and maintenance in the resting state.

Microglial cells constitute what is considered to be a fixed macrophage population in the central nervous system (CNS), which are broadly implicated in the regulation of neuroinflammation. In the normal adult CNS, microglial cells exist in a resting state characterized by a minimal or negative expression of MHC class II and the co-stimulatory molecules CD80, CD86 and CD40 and exhibit a unique ramified morphology. Microglial cell activation is associated with many inflammatory and neurogenerative CNS pathologies and is characterized by the transformation of resting microglia into cells with a macrophage morphology and up-regulation of MHC class II and co-stimulatory molecules. The cellular and molecular mechanisms required for microglial cell activation and their immunological functions in the adult brain still remain enigmatic, primarily due to the lack of an appropriate culture system that both facilitates microglial survival and expansion in the resting state. Here, we describe a new M-CSF-dependent culture system that overcomes these barriers and allows the long-term proliferation and maintenance of resting adult microglial cells isolated from the CNS. These cultured microglial cells retain their plasticity as indicated by their ability to up-regulate MHC class II and differentiate into cells with a macrophage morphology following the addition of IFN-gamma and GM-CSF, or activated T cells, which produce both cytokines. By measuring the proliferation of the T cells, we were also able to demonstrate that the microglial cells differentiated into fully functional antigen presenting cells. In addition, the replacement of the M-CSF with GM-CSF resulted in the differentiation of microglial cells into cells morphologically and phenotypically similar to dendritic cells. Our microglial cell culture system is the first described that allows the expansion of adult cells in the resting state and will facilitate studies examining the specific mechanisms of microglial cell activation and functions involved in a variety of CNS pathologies.

Animals↗

Altered resting-state functional connectivity patterns of anterior cingulate cortex in adolescents with attention deficit hyperactivity disorder.

Dorsal anterior cingulate cortex (dACC) has been found to function abnormally in attention deficit hyperactivity disorder (ADHD) patients in several former functional MRI (fMRI) studies. Resting-state low-frequency fluctuations (LFFs) of blood oxygen level-dependent (BOLD) fMRI signals have been proved to be quite informative. This study used resting-state LFFs to investigate the resting-state functional connectivity pattern differences of dACC in adolescents with and without ADHD. As compared to the controls, the ADHD patients exhibited more significant resting-state functional connectivities with the dACC in bilateral dACC, bilateral thalamus, bilateral cerebellum, bilateral insula and bilateral brainstem (pons). No brain region in the controls was found to exhibit more significant resting-state functional connectivity with the dACC. We suggest these abnormally more significant functional connectivities in the ADHD patients may indicate the abnormality of autonomic control functions in them.

Adolescent↗

Quantitative relationship of stress Tc-99m sestamibi lung uptake with resting Tl-201 lung uptake and with indices of left ventricular dysfunction and coronary artery disease.

BACKGROUND: We investigated the relationship of stress technetium 99m sestamibi lung uptake with rest thallium 201 lung uptake and with indices of left ventricular (LV) dysfunction and severity of coronary artery disease (CAD) in patients with known or suspected CAD undergoing stress testing and cardiac catheterization. Stress Tc-99m sestamibi lung uptake and both stress and rest Tl-201 lung uptake are associated with LV dysfunction and extent of CAD. Although the mechanism of lung uptake is thought to be similar for the two isotopes, their physiologic characteristics are different. No direct comparison of lung uptake for the two isotopes has been reported. METHODS AND RESULTS: We evaluated 192 consecutive patients who underwent dual-isotope myocardial perfusion imaging and cardiac catheterization within 30 days. We examined the relationship of stress Tc-99m sestamibi lung-to-heart ratio (LHR) with rest Tl-201 LHR, with indices of myocardial perfusion, and with invasive measures of the severity of LV dysfunction and CAD. Stress Tc-99m sestamibi LHR correlated with rest Tl-201 LHR (r = 0.548, P <.001). Stress Tc-99m sestamibi LHR was positively associated with LV filling pressures and extent of CAD and negatively associated with LV ejection fraction and arterial systolic blood pressure. However, after adjustment for multiple comparisons, stress Tc-99m sestamibi LHR was significantly associated only with LV end-diastolic pressure (r = 0.287, P =.002) and pulmonary capillary wedge pressure (r = 0.337, P <.001). CONCLUSIONS: Increased stress Tc-99m sestamibi LHR correlates with rest Tl-201 LHR in patients with known or suspected CAD. Stress Tc-99m sestamibi lung uptake is also associated with invasively measured LV filling pressures.

Coronary Artery Disease↗

Balancing work and rest to combat driver fatigue: an investigation of two-up driving in Australia.

This study is the fourth in a series examining driver fatigue in the Australian long distance road transport industry. Thirty-seven long haul truck drivers were measured on a routine 4500 km round trip. Two types of driving operations were compared, single driving, involving a solo driver, and two-up driving, where a pair of drivers operate a truck continuously and alternate between work and rest. Two-up drivers reported higher levels of fatigue than single drivers overall and tended to show poorer levels of performance. However, this result appeared to reflect differential fatigue at the start of the trip. Both two-up and single drivers showed marked increases in fatigue across the first half of the trip, followed by a substantial recovery of alertness and performance provided that drivers had stationary overnight rest at mid trip or had shorter trips. Fatigue continued to increase on the second half of the trip for drivers who did longer trips without the benefit of a substantial night rest or who did not have access to on-board rest, that is single drivers. The use of overnight rest, in combination with two-up driving, appeared to be the most successful strategy for managing fatigue across the trip.

Accidents, Occupational↗

Hemodynamic effects of alinidine (ST 567) at rest and during exercise in patients with chronic congestive heart failure.

Selective inhibition of sinus node function offers the possibility to decrease heart rate and reduce myocardial oxygen consumption in patients with impaired cardiac function, if myocardial contractility is not further attenuated. To study the influence of a specific sinus node inhibitor on myocardial function, alinidine was given to 10 patients with chronic congestive heart failure and stable sinus rhythm. Radionuclide ventriculography was used to monitor left ventricular function at rest and during a standardized exercise protocol. After a bolus injection of 45 mg of alinidine followed by infusion of 10 mg/hr, radionuclide studies were repeated 1.5 and 3 hours later. The results show that left ventricular ejection fraction, stroke volume, and end-diastolic volume index were essentially unchanged, whereas cardiac index decreased by 10% at rest and during exercise. Heart rate decreased markedly by 14% at rest and by 13% during exercise. Systolic blood pressure was reduced by 6% at rest and by 14% during exercise. As a result of the marked decrease of these two parameters, a pronounced effect was seen on rate-pressure product with a 19% decrease at rest and a 24% decrease during exercise. No significant side effects were observed. Alinidine might be given to patients with chronic congestive heart failure and sinus rhythm in doses up to 45 mg without exerting a clinically relevant negative inotropic effect. Therefore it may represent an alternative to other drugs when a decrease in heart rate is desired to reduce myocardial oxygen consumption.

Aged↗

Changes in mood status and neurotic levels during a 20-day bed rest.

This study evaluated changes of mood status and depressive and neurotic levels in nine young male subjects during a 20-day 6 degrees head-down tilting bed rest and examined whether exercise training modified these changes. Participants were asked to complete psychometrical inventories on before, during, and after the bed rest experiment. Depressive and neurotic levels were enhanced during bed rest period according to the Japanese version of Zung's Self-rating Depression Scale and the Japanese version of the General Health Questionnaire. Mood state "vigor" was impaired and "confusion" was increased during bed rest and recumbent control periods compared to pre-bed rest and ambulatory control periods according to the Japanese version of Profiles of Mood State, whereas the mood "tension-anxiety", "depression-dejection", "anger-hostility" and "fatigue" were relatively stable during experiment. Isometric exercise training did not modify these results. Microgravity, along with confinement to bed and isolation from familiar environments, induced impairment of mental status.

Adaptation, Psychological↗

The NASA Performance Assessment Workstation: cognitive performance during head-down bed rest.

The NASA Performance Assessment Workstation was used to assess cognitive performance changes in eight males subjected to seventeen days of 6 degrees head-down bed rest. PAWS uses six performance tasks to assess directed and divided attention, spatial, mathematical, and memory skills, and tracking ability. Subjective scales assess overall fatigue and mood state. Subjects completed training trials, practice trials, bed rest trials, and recovery trials. The last eight practice trials and all bed rest trials were performed with subjects lying face-down on a gurney. In general, there was no apparent cumulative effect of bed rest. Following a short period of performance stabilization, a slight but steady trend of performance improvement was observed across all trials. For most tasks, this trend of performance improvement was enhanced during recovery. No statistically significant differences in performance were observed when comparing bed rest with the control period. Additionally, fatigue scores showed little change across all periods.

Adult↗

Plasma volume and biochemical changes in athletes during bed rest chronic hyperhydration.

Daily fluid and salt supplements (FSS) may be used to reduce plasma biochemical changes during bed rest (BR). The aim of this study was to evaluate the effect of a daily intake of FSS on plasma volume (PV) and biochemical changes during BR. Studies were done during a pre BR period of 15 days and during a BR period of 30 days. Thirty male athletes aged 22-26 years were chosen as subjects. They were divided into three groups: unsupplemented ambulatory control subjects (UACS), unsupplemented bed rested subjects (UBRS) and supplemented bed rested subjects (SBRS). The UBRS and SBRS were kept under a rigorous bed rest regime for 30 days. The SBRS took 26 ml water/kg body weight and 0.1 g sodium chloride/kg body weight daily. PV, protein, albumin, sodium (Na), Chloride (Cl), potassium (K), osmolality, creatinine, glucose, and whole blood haematocrit (Hct) and haemoglobin (Hb) concentrations were measured. PV increased significantly (P < or = 0.01) while plasma protein, albumin. Na, Cl, K, glucose, creatinine, osmolality, and whole blood Hb and Hct concentration decreased significantly (P < or = 0.01) in the SBRS group when compared with the UBRS group. By contrast, PV decreased significantly (P < or = 0.01), while plasma protein, albumin, Na, Cl, K, glucose, creatinine, osmolality and whole blood Hct and Hb concentration increased significantly (P < or = 0.01) in the UBRS group when compared with the SBRS and UACS groups. The measured parameters did not change significantly in the UACS group when compared with the baseline control values. It was concluded that a daily intake of FSS may be used to attenuate PV losses and biochemical changes in endurance trained athletes during bed rest.

Adult↗

The ulcerogenic effect of a rest period after exposure to water-restraint stress in rats.

Shock-induced gastric ulceration in rats is exacerbated by allowing animals to rest between the period of stress and sacrifice. Conflicting data have been reported for similar post-stress rest effects using restraint stress. In Experiment 1, rats restrained in water for 2 h and then allowed a 2-h rest period exhibited significantly greater gastric ulceration than rats sacrificed immediately after the 2-h restraint-in-water stress period. The strength of this phenomenon is confirmed by Experiment 2, in which rats challenged with restraint in water for 1.25 h and then allowed a 1.25-h rest period before sacrifice exhibited greater ulceration than animals maintained in the restraint-in-water stress for the full 2 1/2 h. Corticosterone levels for these two treatment groups were similar at the time of sacrifice. Post-stressor rest therefore actively contributes to the ulcerogenic processes initiated by this form of stress challenge.

Animals↗

Transcutaneous electrical nerve stimulation (TENS) improves the rest-activity rhythm in midstage Alzheimer's disease.

Nightly restlessness in patients with Alzheimer's disease (AD) is probably due to a disorder of circadian rhythms. Transcutaneous electrical nerve stimulation (TENS) was previously reported to increase the strength of coupling of the circadian rest activity rhythm to Zeitgebers in early stage Alzheimer's disease (AD) patients. It was investigated in the present study whether TENS could also improve the rest activity rhythm of patients in a midstage. Sixteen patients who met the NINCDS ADRDA criteria for probable AD, and the stage 6 criteria of the Global Deterioration Scale were treated with TENS or placebo. Rest activity rhythm was assessed using actigraphy. Compared to the control group, stimulated patients showed an improvement in the rest activity rhythm of similar magnitude as observed previously in patients in an early stage. It is concluded that TENS increased the coupling between the rest activity rhythm and supposedly stable Zeitgebers in an advanced stage of AD.

Aged↗

Determinants of symptoms and exercise capacity in aortic stenosis: a comparison of resting haemodynamics and valve compliance during dobutamine stress.

AIMS: Valve compliance might determine the onset of symptoms better than resting measures of aortic stenosis. This study compared valve compliance measured by dobutamine stress echocardiography with resting haemodynamic variables against the end-point of symptoms at low workload during exercise testing. METHODS AND RESULTS: Echocardiography was performed at rest and during each stage of a dobutamine stress test in 65 asymptomatic patients with moderate or severe aortic stenosis. Each patient also completed a modified Bruce treadmill exercise test. During dobutamine stress, peak transaortic velocity increased by 1.0 (0.4) m/s and effective orifice area by 0.25 (0.22) cm(2). Valve compliance was 0.23 (0.10) cm(2)/100ml.s(-1), and was independent of baseline effective orifice area. In the 19 patients limited by symptoms on exercise testing, valve compliance was significantly lower (0.19 (0.09) cm(2)/100ml.s(-1)) than in those who remained asymptomatic (0.25 (0.10) cm(2)/100ml.s(-1), p=0.03). Effective orifice area at peak stress was also lower (1.0 (0.3) vs 1.2 (0.4) cm(2), p=0.03), but there were no significant differences in resting measures of effective orifice area, transaortic velocity, or mean pressure drop. CONCLUSIONS: Effective orifice area is flow-dependent in patients with moderate and severe aortic stenosis with preserved left ventricular function. Exertional symptoms are better predicted by compliance than resting effective orifice area, mean pressure drop or peak transaortic velocity.

Adult↗

Regional myocardial dysfunction in patients with angina at rest and response to isosorbide dinitrate assessed by phase analysis of radionuclide ventriculograms.

Left and right ventricular synchrony was assessed in 15 patients with angina at rest but no previous infarction by phase analysis of equilibrium radionuclide ventriculograms. Transient thallium-201 perfusion defects were noted in all during angina at rest and coronary vasospasm was documented in nine of the patients. Radionuclide ventriculograms were performed at control, during the ischemic episodes and after intravenous isosorbide dinitrate. Left and right ventricular phase histograms were quantified by the standard deviation from the mean of the peak (SD). Left ventricular ejection fraction averaged 65 +/- 11% (mean +/- standard deviation) at control, decreased in all patients during angina at rest to 49 +/- 14% (p less than 0.01) and increased in all patients after isosorbide dinitrate to 66 +/- 12%. However, ejection fraction during ischemia was abnormal in only nine patients and changed in two by less than 5% from the control value. Regional wall motion abnormalities were noted in all patients during the ischemic episodes but resolved after isosorbide dinitrate administration. Control left ventricular SD was 14.5 +/- 4 degrees, increased in all patients to 22.8 +/- 5 degrees during angina at rest (p less than 0.01) and returned to control values after isosorbide dinitrate administration (14.2 +/- 4 degrees). In contrast, right ventricular SD did not significantly change during ischemia as compared with control and isosorbide dinitrate. It is concluded that in angina at rest, a normal left ventricular ejection fraction does not exclude severe regional dysfunction; separate left and right ventricular SD is a sensitive index in detecting transient left ventricular dysfunction, and relief of ischemia is associated with rapid normalization of regional left ventricular function.

Adult↗

Reversal of rest myocardial asynergy during exercise: a radionuclide scintigraphic study.

UNLABELLED: While exercise-induced segmental left ventricular wall motion abnormalities are well described, the phenomenon of improvement in certain asynergic segments during exercise in some patients remains a curiosity. To assess this unexpected finding, results were analyzed in 85 patients with wall motion abnormalities at rest who underwent two view (45 degrees left anterior oblique and anterior) exercise radionuclide ventriculography and exercise thallium-201 myocardial perfusion imaging. Wall motion was scored with a 5 point system (from 3 [normal] to - 1 [dyskinesia]); normalization or increase of 2 or more points with exercise signified improvement. Forty-eight patients (56%) had no change or further deterioration of wall motion at peak exercise, 15 (18%) showed both improvement of wall motion and deterioration and 22 (26%) showed only improvement of wall motion. Wall motion improvement during exercise was found in 57 (20%) of 279 segments with asynergy at rest. Of these 57 segments improving with exercise, 45 (79%) showed mild and 12 (21%) showed severe asynergy at rest. Only seven segments (12%) were associated with pathologic Q waves. Thallium-201 perfusion was normal in 44 segments (77%) while only 6 segments (11%) had reversible and only 7 (12%) had nonreversible thallium-201 defects. IN CONCLUSION: 1) wall motion that is abnormal at rest can sometimes improve with exercise; 2) this phenomenon generally occurs in zones without a Q wave or nonreversible thallium-201 defect. Hence, segments with abnormal wall motion at rest that show improvement with exercise appear to represent viable nonischemic segments.

Adult↗

Exercise echocardiography: detection of coronary artery disease in patients with normal left ventricular wall motion at rest.

Most studies investigating the ability of exercise two-dimensional echocardiography to identify patients with coronary artery disease have included patients with left ventricular wall motion abnormalities at rest. This has the effect of increasing sensitivity because patients with only abnormalities at rest are detected. To determine the diagnostic utility of exercise echocardiography in patients with normal wall motion at rest, 64 patients were studied with exercise echocardiography in conjunction with routine treadmill exercise testing before coronary cineangiography. All 24 patients who had no angiographic evidence of coronary artery disease had a negative exercise echocardiogram (100% specificity). Nine of 40 patients with coronary artery disease (defined as greater than or equal to 50% narrowing of at least one major vessel) also had a negative exercise echocardiogram (78% sensitivity). Of the nine patients with a false negative exercise echocardiographic study, six had single vessel disease. Among 25 patients with single vessel disease, exercise echocardiography was significantly more sensitive (p = 0.01) than treadmill exercise testing alone (76 versus 36%, respectively). Among 15 patients with multivessel disease, the two tests demonstrated similar sensitivity (80%). In conclusion, exercise echocardiography is highly specific and moderately sensitive for the detection of coronary artery disease in patients with normal wall motion at rest. Although exercise echocardiography is significantly more sensitive than treadmill exercise electrocardiographic testing alone in patients with single vessel disease, the two tests are similar in their ability to detect coronary artery disease in patients with multivessel disease and normal wall motion at rest.

Adult↗

Dietary preparation before rest and exercise testing.

To compare the effectiveness of four dietary preparations for stabilizing resting and exercise measurements, seven male recreational exercisers (27 +/- 4 y) participated in four dietary preparations, each repeated in successive weeks: (1) 24-h random diet including an overnight fast (RAN); (2) 24-h random diet, including fast, followed by a standard meal 3 h before testing (RANM); (3) 24-h prescribed diet including an overnight fast (PRES); and (4) 24-h prescribed diet, including fast, followed by a standard meal (PRESM). After each preparation, metabolic rate (VO2) and respiratory exchange ratio (RER) were measured at rest and in association with moderate treadmill exercise. Plasma was analyzed for glucose, cholesterol, and high-density lipoprotein (HDL)-cholesterol. Repeated measures analyses of variance (ANOVAs) followed by Tukey posthoc tests indicated that resting VO2, RER, and blood parameters were not different between the two trials on the same diet. Exercise RER, however, was slightly different in trial 1 than in trial 2 for all preparations except PRESM. Combining both trials, resting VO2 and exercise RER were higher when a pretesting meal was administered. Plasma values were not different for the four dietary preparations. These results suggest that a standard overnight fast appears to be adequate for establishing representative and reproducible rest and exercise values for the parameters measured, except possibly for exercise RER reliability.

Adult↗

Attenuation of the protein wasting associated with bed rest by branched-chain amino acids.

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest.

Adult↗

Clozapine's effects on body weight and resting metabolic rate: a case series.

The purpose of this pilot study is to determine if an association exists between clozapine-associated weight gain and resting metabolic rate (RMR). In doing so, we used a "pretest-posttest" single group design in which we measured resting metabolic rate and total body weight prior to implementing clozapine therapy and then again approximately 1 month after initiating clozapine therapy. The results of three patients treated with clozapine revealed an inverse relationship between resting metabolic rate and total body weight. Resting metabolic rates were notably reduced by 10.3-16.0% whereas total body weights had increased between 2.9 and 9 kg. To our knowledge, this is the first documentation of an antipsychotic medication being associated with the reduction in resting metabolic rate.

Adult↗