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PubMed1991

Myocardial mechanics predict hemodynamic performance during normal function and alcohol-induced dysfunction in rats.

To determine whether mechanical evaluation of muscle tissue removed from the myocardium can be employed as a direct indicator of cardiac contractile performance in situ, isometric and isotonic parameters of muscle mechanics in vitro were correlated with in vivo global functional characteristics of the same heart. Twelve-month-old animals maintained on standard food and water were employed as representative of normal cardiac function. Animals of identical age with left ventricular (LV) dysfunction induced by oral alcohol (30%) ingestion from 4 to 12 mo were utilized to represent depressed cardiac performance. Accordingly, 24 h after the establishment of the hemodynamic profile for a control or experimental heart, the LV posterior papillary muscle was removed from the same heart and examined isometrically and isotonically. Least squares regression analysis was employed to establish a correlation coefficient and P values between various in vitro and in vivo parameters. Hemodynamic measurements were performed under chloral hydrate anesthesia and LV pump performance was evaluated with respect to aortic and ventricular pressures and the rates of rise and decay of the LV pressure trace. Papillary muscles were evaluated with respect to timing parameters of the isometric and isotonic twitch, the first derivative of isometric tension development, and the speed of muscle shortening at increasing physiologic loads. LV peak rate of pressure rise and decay were then correlated with the various isometric and isotonic properties. Myocardial mechanics and hemodynamics revealed depressed function in the papillary muscles and hearts from alcoholic rats. Moreover, significant correlations were found between the LV rate of pressure change (peak +dP/dt and -dP/dt) and both isometric and isotonic twitch measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

PubMed1998

Evaluation of regional systolic function in hypertrophic cardiomyopathy and hypertensive heart disease: a three-dimensional echocardiographic study.

Assessment of regional left ventricular (LV) function in patients with asymmetric LV hypertrophy is difficult with two-dimensional echocardiography mainly because of factors such as LV geometry, structure, regional wall stress, and ischemia. Multiplane transesophageal echocardiography with three-dimensional reconstruction of cross-sectional images was used for quantitative evaluation of regional wall thickness and fractional thickening. Fifteen patients (56 +/- 13 years old) with hypertrophic cardiomyopathy (LV ejection fraction 71% +/- 4%), 15 (62 +/- 13 years) with hypertensive heart disease (ejection fraction 66% +/- 8%) and 15 (53 +/- 11 years) healthy control subjects (ejection fraction 61% +/- 5%) were included in the analysis. Regional function was studied in four parallel equidistant short-axis cross sections from base to apex of the reconstructed left ventricle. In 15 degree intervals, 24 wall thickness measurements in each cross section were made at end-diastole and end-systole after endocardial and epicardial border tracing. A total of 192 measurements were obtained in each patient, and absolute wall thickening and fractional thickening were calculated. Absolute and fractional wall thickening showed a significant inverse relation to end-diastolic wall thickness in all heart conditions (r = 0.71, p < 0.0001). Regions of normal wall thickness in diseased patients were not hyperdynamic when compared with normal control subjects. Significant impairment in fractional thickening at identical end-diastolic thickness was observed in the septum compared with the lateral free wall in both hypertrophic cardiomyopathy and hypertensive heart disease. Thus regional systolic function is inversely related to end-diastolic wall thickness. The decrease in regional systolic function with increasing LV hypertrophy was similar in idiopathic and hypertensive cardiomyopathy. In both types of hypertrophy, significant differences in systolic function were observed in septal and lateral wall segments of similar wall thickness. This indicates that factors other than end-diastolic wall thickness influence myocardial thickening in patients with hypertrophy and preserved global function.

Cardiomyopathy, Hypertrophic↗

PubMed1997

Segmental analysis of color kinesis images: new method for quantification of the magnitude and timing of endocardial motion during left ventricular systole and diastole.

BACKGROUND: We describe a method for objective assessment of left ventricular (LV) endocardial wall motion based on Color Kinesis, a new echocardiographic technique that color-encodes pixel transitions between blood and myocardial tissue. METHODS AND RESULTS: We developed a software that analyzes Color Kinesis images and provides quantitative indices of magnitude and timing of regional endocardial motion. Images obtained in 12 normal subjects were used to evaluate the variability in each index. Esmolol, dobutamine, and atropine were used to track variations in LV function in 14 subjects. Objective evaluation of wall motion was tested in 20 patients undergoing dobutamine stress testing. Regional fractional area change, displacement, and radial shortening were displayed as histograms and time curves. Global function was assessed by calculating magnitude and timing of peak ejection or filling rates and mean time of ejection or filling. Patterns of endocardial motion were consistent between normal subjects. Fractional area change and peak ejection rate decreased with esmolol and increased with dobutamine. Time to peak ejection and mean time of contraction were prolonged with esmolol and shortened with dobutamine. Using atropine, we proved that our findings with dobutamine were not secondary to its chronotropic effects. Dobutamine induced regional wall motion abnormalities in 10 patients in 38 segments diagnosed conventionally. Segmental analysis detected abnormalities in 36 of these 38 segments and in an additional 5 of 322 segments. CONCLUSIONS: Analysis of Color Kinesis images allows fast, objective, and automated evaluation of regional wall motion sensitively enough to evaluate clinical dobutamine stress data. This method has significant potential in the diagnosis of myocardial ischemia.

Adrenergic beta-Agonists↗

PubMed1998

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group.

The efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD) was investigated in a multicenter, double-blind study. Patients were randomly assigned to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154), or 10 mg/d donepezil (n = 157) for 24 weeks followed by a 6-week, single-blind placebo washout. The primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinician's Interview Based Assessment of Change-Plus (CIBIC plus), with the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB), and patient rated Quality of Life (QoL) used as secondary measures. Cognitive function, as measured by the ADAS-cog, was significantly improved in the 5- and 10-mg/d donepezil groups as compared with the placebo group at weeks 12, 18, and 24. Clinician's global ratings on the CIBIC plus also improved in both the 5- and 10-mg/d donepezil groups relative to placebo. At the end of the 6-week placebo washout phase, ADAS-cog scores and CIBIC plus ratings were not significantly different for the three groups. Significant treatment benefits were also observed consistently in both the 5- and 10-mg/d groups on the MMSE and the CDR-SB, but there was no consistent effect on the patient-rated QoL. Cholinergic side effects (primarily diarrhea, nausea, and vomiting) were reported more often in the 10-mg/d group than either the 5-mg/d or placebo groups. Side effects were transient and generally mild in severity. These data indicate that donepezil is a well-tolerated drug that improves cognition and global function in patients with mild to moderate AD.

Aged↗

PubMed1984

Vasoconstrictor systems supplying skeletal muscle, skin, and viscera.

Stimulation of afferent inputs from the body surface and from the interior of the body elicits distinct reflex patterns in post- and preganglionic vasoconstrictor neurons supplying skeletal muscle, skin and viscera of the cat. These patterns are due to characteristic organizations of the vasoconstrictor systems in the neuraxis and may serve as functional labels for the neurons but also as conceptual leads in experimental investigations of the vasoconstrictor systems in the neuraxis. These systems may be generally organized in a hierarchical manner. The lowest level of the hierarchy consists of separate common final sympathetic pathways, the pre-postganglionic channels, with some integrating processes in the ganglia. Then there is the spinal level with the spinal sympathetic motor units. Different functional motor units overlap and receive their inputs from the periphery via primary afferents and from brain stem and hypothalamus via spinal descending systems. Brain stem and hypothalamus organize spinal motor units into global functional units.

Animals↗

PubMed1993

Dimensions and predictors of change during brief psychiatric hospitalization.

The effects of brief psychiatric hospitalization on patient functioning remain controversial and poorly defined. In this study, 217 subjects were evaluated for the changes they experienced during a brief admission (average length of stay 23.0 +/- 16.2 days). Significant improvements occurred in symptoms, global functioning, self-esteem, perceptions of others, and ego functioning. Better multidimensional outcome correlated with symptomatic improvement and preadmission functioning. No effects were found for age, gender, Axis I diagnosis, presence of an Axis II or Axis III disorder, prior hospitalization, severity of symptoms, length of stay, or payor group. During brief hospitalization, patients appear to improve in several areas of psychosocial functioning.

Adolescent↗

PubMed2005

Early behavioral symptoms and course of Alzheimer's disease.

OBJECTIVE: To determine if behavioral symptoms detected at initial evaluation relate to cognitive or functional status or survival time in Alzheimer's disease (AD) patients. method: Review, in 100 cases of autopsy-proven AD, of the relationship of behavioral symptoms detected at initial evaluation to cognitive and global function measures and survival time. RESULTS: Behavioral symptoms had occurred in 74% of patients, including apathy (51%), hallucinations (25%), delusions (20%) and depressed mood (6.6%). Verbal aggression was common (36.8%); physical aggression less so (17%). The symptomatic group was more functionally (but not cognitively) impaired and had shorter median survival time (8 years: 95% CI: 7-9 years vs. 10 years: 95% CI: 8-12 years; P = 0.002) than the asymptomatic group. The presence of any one symptom at initial evaluation accounted for 6.1% of the variance in duration of illness. CONCLUSION: Presence of behavioral symptoms at initial evaluation of AD patients is associated with greater functional impairment and shorter survival time.

Aged↗

PubMed2005

Incremental value of strain rate analysis as an adjunct to wall-motion scoring for assessment of myocardial viability by dobutamine echocardiography: a follow-up study after revascularization.

BACKGROUND: Assessment of myocardial viability based on wall-motion scoring (WMS) during dobutamine echocardiography (DbE) is difficult and subjective. Strain-rate imaging (SRI) is quantitative, but its incremental value over WMS for prediction of functional recovery after revascularization is unclear. METHODS AND RESULTS: DbE and SRI were performed in 55 stable patients (mean age, 64+/-10 years; mean ejection fraction, 36+/-8%) with previous myocardial infarction. Viability was predicted by WMS if function augmented during low-dose DbE. SR, end-systolic strain (ESS), postsystolic strain (PSS), and timing parameters were analyzed at rest and with low-dose DbE in abnormal segments. Regional and global functional recovery was defined by side-by-side comparison of echocardiographic images before and 9 months after revascularization. Of 369 segments with abnormal resting function, 146 showed regional recovery. Compared with segments showing functional recovery, those that failed to recover had lower low-dose DbE SR, SR increment (DeltaSR), ESS, and ESS increment (DeltaESS) (each P<0.005). After optimal cutoffs for the strain parameters were defined, the sensitivity of low-dose DbE SR (78%, P=0.3), DeltaSR (80%, P=0.1), ESS (75%, P=0.6), and DeltaESS (74%, P=0.8) was better though not significantly different from WMS (73%). The specificity of WMS (77%) was similar to the SRI parameters. Combination of WMS and SRI parameters augmented the sensitivity for prediction of functional recovery above WMS alone (82% versus 73%, P=0.015; area under the curve=0.88 versus 0.73, P<0.001), although specificities were comparable (80% versus 77%, P=0.2). CONCLUSIONS: The measurement of low-dose DbE SR and DeltaSR is feasible, and their combination with WMS assessment improves the sensitivity of viability assessment with DbE.

Aged↗

PubMed1998

[Obtaining myo-cardial perfusion images synchronized with the ECG (gated-SPEC) after injecting MIBI during exertion: comparative study with echocardiography in 95 patients for the assessment of left ventricular function].

Technical innovation has recently resulted in the routine use of gated-SPECT in myocardial perfusion imaging. In the present work we compare estimates of left ventricular function (LV cavity) by gated-SPECT with those of conventional echocardiography in a group of 95 ischemic patients, 49 of whom had previous myocardial infarction. Kappa analysis showed correlation coefficients of 0.67 for global function in the whole group and of 0.68 in patients with MI, as well as of 0.56 in the anterior wall, and 0.55 in the inferior wall. With these data, we believe that the technique is useful and it adds to the conventional perfusion SPECT imaging. Also, it is conveniently validated against echocardiography in our hands.

Adult↗

PubMed1994

[Significance of the persistence of ST segment elevation in anterior infarction].

OBJECTIVE: Persistent ST segmentary elevation in anterior myocardial infarction was classically attributed to ventricular aneurysm. This association is now considered controversial. We studied the association between this electrocardiographic finding and the left ventricular wall motion abnormalities and global function. DESIGN: Retrospective study. SETTING: Patients admitted to Hospital de Pulido Valente Coronary Care Unit in Lisbon with anterior myocardial infarction who were submitted to angiographic study. PATIENTS: 94 patients were included in the study. METHODS: The global ejection fraction, the regional wall motion abnormalities, the coronary artery disease extension, the patency and the proximal involvement of the left anterior descending artery were investigated. RESULTS: 56 of the 94 patients (60%) had persistent ST segment elevation and 38 (40%) had isoelectric ST segment. The ejection fraction was markedly depressed in the group with elevated ST segment (36.2 SD 17.6) in contrast with the group with isoelectric ST segment (49.3 SD 14.8) (p < 0.001). The group with persistent ST segment elevation had more advanced degrees of left ventricular asynergy (42/58-75%) than the group with isoelectric ST segment (12/38-32%) (p = 0.02). The other studied angiographic variables did not differ between the two groups. CONCLUSIONS: The group with persistent ST segment elevation was associated with advanced degrees of left ventricular asynergy and greater left ventricular function depression. The ventricular aneurysm was exclusive of the first group.

Adult↗

PubMed2003

Effects of intra-abdominal CO2-insufflation on normal and impaired myocardial function: an experimental study.

BACKGROUND: Intra-abdominal pressure (IAP) elevation during CO2-pneumoperitoneum increases cardiac afterload and may enhance dysfunction of the already compromised heart. This study focused on the effects of acute IAP increases on left and right ventricular loadings and contractility in the heart with impaired global function. METHODS: Impairment of myocardial function (IMF) was pharmacologically induced in 16 pigs by administration of halothane and propranolol, while baseline arterial pressure was maintained by intravenous phenylephrine. Intra-abdominal pressure was gradually increased by 10 mmHg up to 30 mmHg in the supine position (IMF group 1, n = 8) or in a head-down tilted position (IMF group 2, n = 8). In two control groups with normal myocardial function, IAP was also increased in the supine position or the head-down tilted position. Cardiac function in all groups was assessed by epicardial echocardiography, intraventricular pressure measurements and pulmonary artery catheterization. RESULTS: The increase in IAP was accompanied by a transient rise in LV end-systolic wall stress and reduced cardiac output significantly by 16-24% in all groups. In the IMF groups, LV end-diastolic transmural pressure increased by 34-60% to peak values of 24 mmHg, while cross-sectional LV end-diastolic areas remained unchanged. Increases in right ventricular end-diastolic volume and decreases in right ventricular ejection fraction as well as in cardiac output were most pronounced at IAP 20 mmHg and significantly stronger in both IMF groups than in the control groups (P < 0.001). CONCLUSION: Following the acute elevation of IAP, the right ventricular volume load shifted more extensively in the IMF groups than in the animals with normal myocardial function. Myocardial function in the impaired heart may worsen during IAP elevation due to right ventricular load alterations rather than a LV afterload increase.

Abdomen↗

PubMed2005

Cardiac dyssynchrony analysis using circumferential versus longitudinal strain: implications for assessing cardiac resynchronization.

BACKGROUND: QRS duration is commonly used to select heart failure patients for cardiac resynchronization therapy (CRT). However, not all patients respond to CRT, and recent data suggest that direct assessments of mechanical dyssynchrony may better predict chronic response. Echo-Doppler methods are being used increasingly, but these principally rely on longitudinal motion (epsilonll). It is unknown whether this analysis yields qualitative and/or quantitative results similar to those based on motion in the predominant muscle-fiber orientation (circumferential; epsiloncc). METHODS AND RESULTS: Both epsilonll and epsiloncc strains were calculated throughout the left ventricle from 3D MR-tagged images for the full cardiac cycle in dogs with cardiac failure and a left bundle conduction delay. Dyssynchrony was assessed from both temporal and regional strain variance analysis. CRT implemented by either biventricular (BiV) or left ventricular-only (LV) pacing enhanced systolic function similarly and correlated with improved dyssynchrony based on epsiloncc-based metrics. In contrast, longitudinal-based analyses revealed significant resynchronization with BiV but not LV for the overall cycle and correlated poorly with global functional benefit. Furthermore, unlike circumferential analysis, epsilonll-based indexes indicated resynchronization in diastole but much less in systole and had a lower dynamic range and higher intrasubject variance. CONCLUSIONS: Dyssynchrony assessed by longitudinal motion is less sensitive to dyssynchrony, follows different time courses than those from circumferential motion, and may manifest CRT benefit during specific cardiac phases depending on pacing mode. These results highlight potential limitations to epsilonll-based analyses and support further efforts to develop noninvasive synchrony measures based on circumferential deformation.

Animals↗

PubMed1990

A study of the clinical efficacy of maintenance ECT.

Six cases of maintenance electroconvulsive treatment (ECT) in elderly patients with major mood disorders were followed for 1 to 6 years. Documented duration of illness before instituting maintenance ECT ranged from 6 to 53 years (mean +/- SD = 22 +/- 18 years). Measures of effectiveness and safety of maintenance treatment and measures of functional status were prospectively obtained during periods of outpatient ECT administration, and functional status measures were retrospectively obtained for equivalent pre-ECT periods. Such measures included mean frequency of annual hospital admissions and average annual length of inpatient stay, mean scores on standard rating instruments of global functioning and cognitive performance, the average number of prescribed psychotropic medications, and ratings of affect. Some of the authors' findings support the contention that maintenance ECT may help sustain remission in the course of affective illness.

Aged↗

PubMed1993

Delayed effect of streptokinase on left ventricular function after acute myocardial infarction assessed by equilibrium gated radionuclide angiocardiography.

A blind comparative study was conducted on 80 consecutive patients who were given Streptokinase (SK) or placebo between 3 and 6 hours after the onset of acute myocardial infarction (AMI). Left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR) and regional wall motion (RWM) were evaluated by equilibrium gated radionuclide angiocardiography (EGRA) at 3-5 weeks and 6 months after the onset of AMI. In the anterior AMI SK-group, the mean LVEF values rose from 0.37 at one month to 0.43 at six months, PER (end-diastolic volumes per second) from 1.76 to 2.00, and PFR (end-diastolic volumes per second) from 1.46 to 1.75 (p = 0.01, p < 0.05, and p < 0.05, respectively). In the anterior non-SK group no improvement was seen in any of the LV function parameters. Only a slight improvement was observed in the inferior AMI group, with no significant difference between the treated and non-treated patients. The regional wall motion analysis was in agreement with the global function data. In conclusion, SK treatment given between three and six hours after the onset of anterior AMI may result in some improvement in LV function, which becomes fully appreciable only after the complete resolution of stunning, i.e. after more than one month.

Aged↗

PubMed2000

A simple screening assay for certain fibrinolysis parameters (FIPA).

Hemostasis, the system of generation and degradation of thrombi, consists of coagulation and fibrinolysis. Whereas global assays to study coagulation have existed for many years, there has been no simple, rapid, and economic routine test for the plasmatic fibrinolysis parameters plasminogen activator inhibitor-1, alpha2-antiplasmin, plasminogen, and aprotinin. Here a fast functional global assay for these plasmatic fibrinolytic parameters is presented. However, the present assay is not sensitive to physiological concentrations of prourokinase or tissue-type plasminogen activator. The following assay conditions have been found to be optimal: 50 microL of citrated plasma is incubated with 50 microL of 10 IU urinary-type plasminogen activator (urokinase)/mL, 1.1 mmol/L tranexamic acid, 1% polygelin, 0.1% Triton X-100, phosphate-buffered saline, pH 7.4, for 20 min at 37 degrees C (plasmin generation phase). Then 50 microL of 3 mmol/L HD-Nva-CHA-Lys-pNA, 1.05 mol/L KCl is added, and deltaA (405 nm)/10 min (37 degrees C) is determined, by using a microtiterplate reader (plasmin detection phase). The results are calibrated against pooled normal plasma (100% plasmatic fibrinolytic parameters activity). The intra- and interassay coefficients of variation have been found to be less than 5%. The detection limit (sensitivity) of the functional fibrinolysis assay is 5 % of the normal plasmatic fibrinolysis parameters activity. The normal plasmatic fibrinolysis parameters activity is 100%, sigma = 25%. The plasmatic fibrinolysis parameters activity correlates negatively (r = -0.684) with the plasminogen activator inhibitor-1 activity of patient samples. The plasmatic fibrinolysis parameters assay is a simple, rapid, and economic functional test for several clinical relevant fibrinolysis parameters.

Adolescent↗

PubMed2006

Glia maturation factor gamma (GMFG): a cytokine-responsive protein during hematopoietic lineage development and its functional genomics analysis.

Human hematopoiesis was evaluated using the techniques of controlled stem cell differentiation, two-dimensional gel electrophoresis-based proteomics, and functional genomics. We provide the first report that glia maturation factor gamma (GMFG) is a cytokine-responsive protein in erythropoietin-induced and granulocyte-colony stimulating factor-induced hematopoietic lineage development. Results from global functional genomics analysis indicate that GMFG possesses several other features: hematopoietic tissue-specific gene expression, a promoter concentrated with high-score hematopoiesis-specific transcription factors, and possible molecular coevolution with a rudimentary blood/immune system. On the basis of our findings, we hypothesize that GMFG is a hematopoietic-specific protein that may mediate the pluripotentiality and lineage commitment of human hematopoietic stem cells.

Amino Acid Sequence↗

PubMed2004

Sex differences in functional connectivity in first-episode and chronic schizophrenia patients.

OBJECTIVE: There has been consistent evidence for a lower incidence and milder course of schizophrenia in women, yet there have been very few investigations of sex differences in brain function in this disorder. This study used a new high-temporal-resolution measure of functional brain connectivity to test the prediction that female patients would show relatively greater inter- and intrahemispheric connectivity than male patients, particularly in the early stage of schizophrenia. METHOD: Forty patients with chronic schizophrenia (20 women and 20 men) and 24 patients with first-episode schizophrenia (12 women and 12 men) and their respective matched comparison groups completed a conventional auditory oddball task. Phase synchronous gamma (40 Hz) activity was extracted from EEG recording during the task and time-locked to the oddball (target) stimuli. RESULTS: Chronic schizophrenia subjects showed a reduction in global functional connectivity (lower gamma phase synchrony) relative to their matched healthy subjects. Unexpectedly, this reduction was most apparent in female patients. By contrast, while first-episode patients showed a general reduction in the speed of frontal connectivity, the speed of global connectivity was relatively faster in female patients. CONCLUSIONS: This is the first study to investigate sex differences in schizophrenia that used the functional connectivity measure of gamma phase synchrony. The results suggest that in female patients with schizophrenia, additional breakdowns in brain network connectivity may develop with illness chronicity.

Adult↗

PubMed2004

Treatment of depressed mothers of depressed children: pilot study of feasibility.

Numerous studies have shown that depression is highly familial and impairing and that a history of depression in a parent is the strongest risk factor for depression in a child. Many of the parents in these studies have never received sustained treatment despite histories of recurrent depression. None of the studies have examined the effects of maternal symptom remission on offspring symptom or functioning. We sought to determine the feasibility of treating depressed mothers who brought an offspring for the treatment of depression and to examine the relationship between improved maternal depression and symptomatic improvement and social functioning in their offspring. Nine mothers bringing their offspring for treatment of depression, and who were evaluated and found to be currently depressed, completed a 12-week open trial of interpersonal psychotherapy. Mothers and their depressed offspring were assessed by independent evaluators at weeks 0, 6, and 12 for depressive symptomatology and social functioning. Although the rates of depression were high among the mothers, few eligible mothers agreed to participate. Of the 12 who entered treatment, 9 (75%) completed it. Mothers and offspring improved with regard to depressive symptomatology and global functioning over the course of the trial. Improvement in maternal depression was significantly associated with improvement in offspring functioning but not symptom reduction. Improvement of maternal depression may be associated with improved outcomes in depressed offspring. However, it is difficult to engage depressed mothers in treatment for themselves if they come to the clinic to bring their child for treatment of depression. It may be more feasible to study the effect of improved maternal depression on offspring by sampling depressed mothers coming for their own treatment and then assessing their children over the course of maternal treatment.

Adolescent↗