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Publications and source records attributed to E Page.

At least 19 recordsLinked to original sources
PubMed1996

Cardiac output response to dynamic exercise after atrial switch repair for transposition of the great arteries.

Results from this study showed that patients who underwent successful operation for transposition of the great arteries had no appropriate increase in stroke volume in response to exercise of a nature similar to common recreational activities. The impairment, most likely due to disturbances in both venous return and ventricular systolic function, is compensated for by an increase in peripheral oxygen extraction; however, this increase may not be adequate with maturation or during prolonged exercise when cardiovascular constraints are more important.

Cardiac Output↗
PubMed1996

Maximal blood lactate level acts as a major discriminant variable in exercise testing for coronary artery disease detection in men.

BACKGROUND: The interpretation of exercise stress testing for coronary artery disease detection is affected by the many differences in chosen variables and mathematical methods. We conducted a prospective trial to evaluate a global muscle fatigue parameter--the blood lactate level achieved at maximal exercise--as a method of distinguishing between diseased and nondiseased coronary status. METHODS AND RESULTS: We evaluated 236 consecutive male patients without previous myocardial infarction who had been referred for the diagnosis of coronary artery disease. None of the patients had cardiomyopathy, severe cardiac heart failure, or valvular heart disease. Blood lactate concentration at maximal exercise was measured as well as other classic variables. Correlations between variables and coronary status as assessed by coronary arteriography were described using receiver operating characteristic (ROC) curves and logistic regression analysis. The first four most powerful variables (lactate level, maximal power output, exercise duration, and percentage of maximal predicted heart rate), which are directly representative of the global functional capacity, showed values of 0.777, 0.775, 0.760, and 0.740, respectively, by ROC curve analysis. Mean +/- SD blood lactate level at peak exercise reached 7.68 +/- 2.70 mmol/L in the 153 diseased and 10.56 +/- 2.75 mmol/L in the 83 nondiseased patients (P < .0001). After adjustment for other variables, blood lactate level remained a significant predictor of coronary artery disease by logistic regression analysis (adjusted odds ratio, 1.2; confidence interval, 1.04 to 1.4). CONCLUSIONS: Global muscle fatigue as assessed by lactate levels in the blood at maximal exercise appears to be a powerful distinguisher of diseased and nondiseased coronary status.

Adult↗
PubMed1996

Transient fall in oxygen intake during exercise in congestive heart failure.

We report four cases in which oxygen intake abruptly decreased during a graded exercise test. In all these cases, there was an acute event (arrhythmia, mitral regurgitation) that had very likely resulted in a decrease in cardiac output. These studies provide new evidence of oxygen intake dependence on oxygen transport, even in nonsteady-state situations.

Adult↗
PubMed1995

Standardization of absolute CD4+ lymphocyte counts across laboratories: an evaluation of the Ortho CytoronAbsolute flow cytometry system on normal donors.

The Ortho CytoronAbsolute is a flow cytometer designed to provide direct absolute counts of lymphocytes and their subsets from a single instrument. This study was designed to determine the performance of four geographically separated CytoronAbsolute instruments using 24-h-old, shipped, whole blood samples and to compare the results obtained on the CytoronAbsolute to those obtained using combinations of hematology instruments and other flow cytometers. The absolute count feature of the CytoronAbsolutes located at the four sites were cross calibrated and gave across-site coefficients of variation (CVs) of <4.0% for absolute count and 8.2% for absolute lymphocyte count. The calibration was stable for at least 2 months. Absolute lymphocyte counts and lymphocyte percentage immunophenotypes were determined on blood from 50 healthy human immunodeficiency virus (HIV)-seronegative donors. There were no significant site-to-site differences (each P > .05) in CD3+/CD4+ absolute lymphocyte counts determined on the CytoronAbsolute. In contrast, there was a significant site-to-site difference (P < .001) between sites 2 and 3 and sites 3 and 4 in the absolute CD3+/CD4+ lymphocyte counts determined via the conventional method of combining a flow cytometry-derived percentage with a hematology instrument-derived lymphocyte count. There was no significant difference (P = .388) in CD3+/CD4+ lymphocyte percent determinations between the CytoronAbsolute and the FACScan or Profile II flow cytometers used in this study. These results demonstrate that different operators can cross calibrate CytoronAbsolutes for absolute CD3+/CD4+ lymphocyte subset determinations, even over large geographic distances.

CD4 Lymphocyte Count↗
PubMed1995

Effective communication using a speech aid for a postlaryngectomy patient undergoing regional anesthesia: a case report.

A 73-year-old postlaryngectomy male with a tracheostomy was admitted for bladder biopsy and right retrograde pyelogram. At the preoperative visit, the patient was able to communicate effectively only after the suggestion was made to use his speech aid. The patient was asked to bring his Servox Inton electrolarynx to the operating room. The patient received a spinal anesthetic. Adequate communication during the 150-minute procedure was maintained using his speech aid. Postlaryngectomy voicelessness is a cause of psychological trauma in the postlaryngectomy patient. Different techniques have been proposed for producing sounds. An artificial larynx can be used for the postlaryngectomy patient while, or instead of, learning other types of speech. To prevent the possibility of electrical shock while using a metal encased electrolarynx in conjunction with an electrosurgical unit, we recommend removing the metal housing. When intubating a patient with a speech prosthesis in a surgically created tracheoesophageal puncture, we suggest removing the prosthesis and stenting the tracheoesophageal puncture with a catheter. This will prevent both disloding of the speech prosthesis and closure of the fistula. It is important for the anesthetist to become familiar with speech aids in order to establish effective communication with postlaryngectomy patients.

Aged↗
PubMed1994

[Rehabilitation of patients with chronic cardiac insufficiency. Immediate and midterm effects].

OBJECTIVES: While physical training is known to improve cardiac performance in patients with chronic congestive heart failure, we conducted this study to evaluate the effect of such training programmes. METHODS: The study group included 48 untrained patients with stable chronic heart failure controlled with the same daily oral regimen including 0.25 mg digitoxin, 40 mg furosemide and 50 mg captopril. Halt of the patients (n = 24) entered a physical rehabilitation programme for a 3-week period. Each daily session included passive mobilization of the limbs (10 min), respiratory exercises (10 min) and endurance exercise on an ergometric cycle with a maximum work load of 50, 60 and 70% of the theoretical maximal load for weeks 1, 2 and 3 respectively. The other 24 patients did not change their physical activity level and served as controls. The immediate and medium term effects (3 months after the end of the training programme) were assessed using exercise tests, left ventricular isotopic ejection fraction and plethysmography of the lower limbs. The quality of life was compared using the NYHA functional classification and the Goldsman questionnaire. RESULTS: At the end of the 3-week training period, and compared with the control group, there was a moderate improvement of VO2max (p < 0.02) and a 10% improvement in the ejection fraction (p < 0.05) in the trained patients. There was a clearly significant improvement in the anaerobic threshold and arterial blood flow rate (p < 0.001) and lowered vascular resistance (p < 0.001) and venous tone (p < 0.001). The quality of life was also improved in the training group. However, 3 weeks after the end of the training period, these differences disappeared. CONCLUSION: Patients with chronic heart failure can benefit from physical training showing functional improvement and no deleterious effect on left ventricular function. This beneficial effect is nonetheless temporary and would appear to be due to improved skeletal muscle oxidative capacity and peripheral haemodynamics.

Aged↗
PubMed1994

Comparison of dosage-dependent effects of beta-aminopropionitrile, sodium fluoride, and hydrocortisone on selected physical properties of cortical bone.

BAPN, sodium fluoride, and hydrocortisone are reported to induce altered mineralization states. Three separate sets of experiments, one set for each agent, were performed using male New Zealand white rabbits. In each experiment the rabbits were segregated into groups, each fed a specified weight-determined dose for 13 weeks and then sacrificed. Compact bone from the left femur and tibia were tested for density, composition, sonic velocity, longitudinal elastic modulus, equatorial diffraction spacing of mineralized collagen, diaphyseal cross-sectional area, and relative load stress. beta-Aminopropionitrile (BAPN) induced monotonic degradation of all properties at all dose levels, corresponding to the decreasing density with dosage level. The elastic moduli show a decrease; the equatorial diffraction spacing of the collagen increases. The cross-sectioned diaphysis resembled woven bone. The variability in properties increased with dosage. The total cross-sectional area for a given weight increased, implying that the decreased elastic properties were compensated for by a larger area to support the weight. There was a slight increase in average density and other properties for fluoride-treated rabbits, peaking at 20 mg/kg BW/day. For higher dosages the properties are degraded and the values were much lower at high fluoride dosages than for BAPN. There was no peak for the equatorial diffraction spacing, which increased with dosage. It is inferred that the fluorosed apatite is denser than normal apatitic mineral and therefore has a smaller specific volume. A greater weight fraction of fluorosed mineral has a smaller volume fraction than the equivalent normal apatitic mineral. The bone sections look more normal, except for the porosis. The total cross-sectional area decreases when the bone density increases and then increases as the density falls, again implying that the area required to support body weight depends on the magnitude of the elastic moduli. There was a small change in some of the properties of the bones of the hydrocortisone-treated rabbits, but the effects on others were undetectable within the uncertainty of the procedures. There was no change in the cross-sectional areas of the diaphyses.

Aminopropionitrile↗
PubMed1994

Regulation of ANP secretion by endothelin-1 in cultured atrial myocytes: desensitization and receptor subtype.

We examined endothelin-1 (ET-1) binding and ET-1-regulated atrial natriuretic peptide (ANP) secretion in primary cultures of adult rat atrial myocytes. ET-1 binding was analyzed as a reversible bimolecular reaction, with bimolecular association rate constant = 1.9 x 10(9) M-1.h-1, dissociation rate constant = 0.028 h-1, and a dissociation constant, calculated from these values = 0.015 nM. ET-1 increased ANP secretion with a one-half effective concentration (EC50) of 0.62 nM, which correlated with EC50 receptor occupancy under equivalent experimental conditions (0.75 nM). The secretory response rapidly desensitized (half-time = 10 min at 10 nM ET-1). The time courses for ET-1 binding, ET-1-stimulated secretion, and desensitization were all comparable. Recovery from desensitization was slow and paralleled the recovery of 125I-labeled ET-1 binding. The ETA receptor subtype-selective antagonist, BQ-123, inhibited 125I-ET-1 binding and ET-1-activated ANP secretion with high affinity, whereas the ETB-selective agonists, endothelin-3 and sarafotoxin S6c, inhibited binding with low affinity and did not effectively stimulate ANP secretion. We conclude that 1) ET-1 can stimulate ANP secretion by direct action on the atrial myocytes; 2) primary cultures of adult rat atrial myocytes express only the ETA receptor subtype; 3) the ANP secretory response to ET-1 desensitizes rapidly but recovers slowly; and 4) occupation of the ETA receptors by ET-1 initiates the unidirectional sequence of receptor activation, signal transduction, ANP secretion, and finally, desensitization.

Animals↗
PubMed1994

Endocytosis and uptake of lucifer yellow by cultured atrial myocytes and isolated intact atria from adult rats. Regulation and subcellular localization.

The time course of endocytic uptake of Lucifer yellow (LY) was followed by fluorescence and electron microscopy after exposure of primary cultures of atrial myocytes from adult rats to LY under conditions that prevented transplasmalemmal LY entry via channels or carriers. After a 2-minute exposure to LY at 37 degrees C, electron microscopy revealed classic clathrin-coated vesicles fused to endosomes, which were absent in LY-free medium or at 2 degrees C, suggesting that LY turns on endocytosis or accelerates a slow constitutive endocytosis. Fluorescence microscopy, which detected no LY entry at 2 minutes in LY, showed punctate cytoplasmic fluorescent densities after 10 minutes, which were readily distinguishable from intrinsic perinuclear fluorescence. Fluorescence microscopy after immunostaining with antibodies against clathrin, vacuolar H(+)-ATPase, atrial peptide, or a marker for acidified compartments suggested LY sorting into an acidified prelysosomal pathway. Using absence of punctate fluorescence after 10 minutes in LY as a criterion for inhibition of endocytosis, we showed that endocytosis was inhibited by inhibitors of protein phosphatases 1 and 2A or inhibitors of cAMP-dependent protein kinases 1 and 2, by effects of caffeine on sarcoplasmic reticulum Ca2+ release, and by temperatures below 18 degrees C, but not by staurosporine, phorbol esters, pertussis toxin, thapsigargin, preventing contractions with nifedipine, ryanodine and low [Ca2+]o, or raising cytosolic cAMP concentrations. Both phosphatase inhibitors and caffeine also inhibited a fraction of LY uptake by intact rat atria. We conclude that endocytic uptake of LY is an energy-dependent, specifically regulated process, whose understanding and control are potentially important for the medically relevant problem of introducing drugs and macromolecules into atrial heart muscle cells.

Animals↗
PubMed1994

Localization of atrial natriuretic peptide in caveolae of in situ atrial myocytes.

The plasma membrane-associated non-clathrin-coated vesicles called caveolae are multifunctional organelles thought to be implicated in the sequestration and transport of small molecules (potocytosis) as well as in the binding of Ca2+ ions, signal transduction, and processing of hormonal and mechanosensitive signals. We have previously suggested that the apparent contiguity of caveolar and atrial granule membranes observed in electron micrographs of in situ mouse atrial myocytes might reflect externalization of atrial natriuretic peptide through caveolae. Using Tokuyasu's classic technique, we now show by immunoelectron microscopy of glutaraldehyde-fixed and cryosectioned mouse and rat atria that antibody against atrial natriuretic peptide prohormone is present within caveolae of in situ atrial myocytes. We confirm this intracaveolar localization by stereoimaging colloidal gold-labeled antibody to the prohormone in electron micrographs of glutaraldehyde/osmium tetroxide-fixed positively stained atrial thin sections. Because profiles of caveolae were rarely immunolabeled with antibody against atrial peptide unless there was a profile of an immunolabeled atrial granule nearby in the subjacent cytoplasm, we concluded that the intracaveolar hormone was derived predominantly from a direct interaction of atrial granules with caveolae. Perturbations that markedly increase the rate of natriuretic peptide secretion via the regulated pathway, including atrial stretch, contractions, and increased external Ca2+ concentration, failed to alter caveolar immunostaining. These results suggest that atrial peptide can pass from atrial granules into caveolae by transiently open pathways between the interiors of granules and caveolae. The results are interpreted as suggesting the presence of a second pathway for externalization of atrial natriuretic peptide through caveolae in addition to the classic pathway for regulated atrial peptide secretion at noncaveolar plasmalemma.

Animals↗
PubMed1994

Comparison of treadmill and bicycle exercise in patients with chronic heart failure.

The general opinion that treadmill exercise elicits circulatory reserve more than bicycle exercise derives from studies conducted in normal subjects or subjects with coronary artery disease. To investigate if this also occurs in patients with chronic heart failure (CHF), 40 patients (mean ejection fraction: 26 +/- 9 percent) with normal pulmonary function underwent in random order both treadmill (Naughton modified protocol, holding on handrails permitted) and bicycle (10 W/min) maximal exercise over a 1-week period. Peak oxygen uptake (19.6 +/- 5.3 vs 17.6 +/- 5.1 ml/min/kg, p < 0.0001), ventilatory threshold (14.4 +/- 4.7 vs 12.0 +/- 3.5 ml/min/kg, p < 0.0001), and minute ventilation (59 +/- 18 vs 55 +/- 15 L/min, p < 0.05) were greater on treadmill than on bicycle. Heart rate, systolic blood pressure, breathing rate, respiratory exchange ratio, perceived exertion scale, and lactate were identical. The coefficient of the correlation between oxygen uptake and time was greater with bicycle than with treadmill (r = 0.97 +/- 0.04 vs 0.90 +/- 0.07, p < 0.001). Thus, treadmill exercise is more suitable for determining peak oxygen uptake in patients with CHF. However, the increase in oxygen uptake is more regular with bicycle exercise.

Anaerobic Threshold↗
PubMed1993

Fluid-phase endocytosis by in situ cardiac myocytes of rat atria.

Fluid-phase endocytosis (FPE) associated with recycling of fused plasmalemma-secretory granules or membranes and/or membrane receptors by in situ cardiac myocytes was studied at 37 degrees C in vitro noncontracting adult rat atrial preparations. Measurements included 1) the volume (VS*) of the compartment consisting of presumptive endocytotic vesicles and the endosomes or lysosomes transiently in continuity with them (S*), which internalizes [14C]-sucrose but is inaccessible to simultaneously measured [methoxy-3H]inulin, 2) the kinetics of [14C]sucrose efflux from S*, and 3) morphometry to quantify interstitial space and non-heart muscle cells. Vs* (0.39 +/- 0.04 ml/g dry atrium for unstretched atria at 37 degrees C) was 1) variable over a 3.7-fold range under various experimental conditions, 2) significantly increased by neomycin or by lowering the temperature to 18 degrees C, and 3) significantly decreased by alpha 1-adrenergic stimulation. Analysis of sucrose efflux kinetics confirmed the presence of an intramyocytic sucrose-containing compartment. A smaller inulin-inaccessible sucrose space (S*) was also present in right ventricle. Thus, during FPE, vesicles and endosomes initially containing high (extracellular) Ca2+ and Cl- concentrations continually enter, circulate within, and undergo exocytosis from myocardial cells.

Animals↗
PubMed1993

Rat atrial myocyte plasmalemmal caveolae in situ. Reversible experimental increases in caveolar size and in surface density of caveolar necks.

The structure, size, and surface density of the conspicuous flask-shaped structures called caveolae that are located under the plasma membrane of cardiac myocytes in intact rat atria were studied by electron microscopy after physiological perturbations designed to examine whether caveolae and/or their necks are fixed or mobile and whether the caveolar lumen is always open or can close off from the interstitial space. We showed that, in stretched and unstretched atria, horseradish peroxidase could enter or be washed out of caveolae at 37 degrees, 18 degrees, and 4 degrees C, but this finding does not rule out that caveolae and/or their necks can cycle rapidly between states closed and open to the interstitial space. Electron microscopy of thin sections revealed that exposure of atria at 37 degrees or 18 degrees C to physiological salt solutions made hypertonic by adding 150 mM sucrose or mannitol resulted in a striking enlargement of caveolar profiles within 1 to 5 minutes. Caveolar enlargement was rapidly reversible on return to control saline. After freeze fracture of atria exposed to these hypertonic solutions, quantitative analysis of electron micrographs of the fracture faces revealed statistically significant increases in cross-sectional diameter of cross-fractured caveolar necks and in mean number of caveolar necks penetrating per unit area of plasmalemmal fracture face. These results suggest that atrial myocyte caveolae are dynamic structures whose necks may be reversibly inserted into and withdrawn from the plasmalemma, possibly (but not necessarily) corresponding to states in which caveolae are, respectively, open and closed to the interstitial spaces.

Animals↗
PubMed1993

[Cardiorespiratory and metabolic changes during prolonged exercise at 50% of the maximal load. Application to rehabilitation of severe cardiac insufficiencies].

The object of physical training in patients with chronic cardiac failure and severe left ventricular dysfunction is to improve skeletal muscle adaptation without impairing myocardial function. It is acknowledged that aerobic exercise limits increased ventricular strain. Therefore, the authors decided to determine whether exercise at 50% maximal power load constituted aerobic training. Eight patients with chronic cardiac failure (age 57 +/- 10 years; resting radionuclide ejection fraction: 25 +/- 5%) performed a rectangular submaximal exercise for 20 minutes at 50% of maximal aerobic load (MAL) as determined by a prior triangular exercise test at 10 W/mn (MAL = 92 +/- 26 Watts-Peak VO2 = 14.8 +/- 2.4 ml/Kg/mn). Gaseous exchanges (VO2, VCO2) minute volume (MV) and serum lactates were measured at rest and every 5 minutes during exercise. MV, VO2 and VCO2 increased significantly (p < 0.005) with a change of less than 5% between the 20th and 10th minute. Respiratory quotient was unchanged until the end of exercise and serum lactate levels stabilised between the 10th (3.4 +/- 0.66 mmol/l) and the 20th minute of exercise (3.5 +/- 0.47 mmol/l). No significant relationship was observed between ventilation and serum lactate or between respiratory quotient and serum lactate. These results confirm that exercise at 50% of maximal load is aerobic training even in patients with severe left ventricular dysfunction. This parameter would appear to be more useful than using the heart rate which is often abnormal in chronic cardiac failure (abnormal chronotropic response, atrial or ventricular arrhythmias).

Aerobiosis↗
PubMed1992

Permeability of rat atrial endocardium, epicardium, and myocardium to large molecules. Stretch-dependent effects.

Atrial distension, which stimulates atrial natriuretic peptide secretion by atrial myocytes, also stretches nonmuscle cells. In a noncontracting in vitro preparation of combined right and left atria we demonstrated by electron microscopy that, at 37 degrees C, transition from zero pressure to a physiological distending pressure of 5.1 mm Hg rapidly rendered atrial endocardial endothelium permeable to the macromolecular probes horseradish peroxidase (HRP; M(r), approximately 40,000) and wheat germ agglutinin-HRP (M(r), approximately 70,000); each probe was introduced at the atrial cavitary endocardial surface. Stretch-dependent permeabilization was also demonstrable in spontaneously contracting atria, was reversed by removing the distending pressure, and was unaffected by varying external Ca2+ concentration from 0.2 to 1.4 mM or by experimental perturbations that markedly decrease ANP secretory rates. Although transendocardial HRP and wheat germ agglutinin-HRP passage required stretch, native ferritin (M(r), = 500,000) could traverse unstretched endocardium. Probes were detected in noncoated endocardial vesicles and intercellular junctions between endocardial cells, but the relative contributions of vesicular transcytosis and paracellular diffusion could not be determined. Although HRP entered plasmalemmal caveolae of myocytes in stretched atria, myocytes did not internalize HRP by fluid-phase endocytosis. Distending pressure also caused apparent flow reversal in thebesian blood vessels, with retrograde transfer of HRP across the endocardium into the myocardium. HRP and ferritin presented at the external surface of the epicardium (visceral pericardium) were endocytosed by mesothelial cells, entered junctions between mesothelial cells, and readily crossed the epicardium of both stretched and unstretched preparations.

Animals↗
PubMed1991

Effect of external Ca2+ concentration on stretch-augmented natriuretic peptide secretion by rat atria.

An in vitro noncontracting rat atrial preparation stretched at 37 degrees C by a distending pressure of 5.1 mmHg was used to examine effects of external Ca2+ concentration ([Ca2+]out, 0.05-3.0 mM) on secretion of immunoreactive atrial natriuretic peptide (ANP) in presence of saxitoxin (STX) and in presence or absence of ryanodine. Under these conditions, the time course of the amount (y) of ANP secreted per milligram dry atrium during 44 min could be approximated by a rate coefficient (k) according to the relation y = s[1 - e(-kt)], where s is the maximal amount secreted after a long time (t). Although k, the rate coefficient for stretch-augmented secretion, increased significantly as [Ca2+]out was raised, secretion inactivated progressively in a time- and [Ca2+]out-dependent manner. This time-dependent decrease was not prevented by ryanodine. We conclude that a component of ANP secreted by quiescent atria in vitro is positively modulated by [Ca2+]out and does not require ryanodine-sensitive Ca2+ release from sarcoplasmic reticulum. The [Ca2+]out-sensitive processes underlying time-dependent inactivation of secretion remain undetermined.

Animals↗
PubMed1991

Inhibition of atrial peptide secretion at different stages of the secretory process: Ca2+ dependence.

We have used a noncontracting in vitro preparation of stretched and unstretched rat atria to estimate contributions of constitutive and regulated pathways to the rates of stretch-augmented and basal secretion of immunoreactive atrial natriuretic peptide (ANP) and to examine effects of inhibition of the secretory sequence by 1) protein synthesis inhibitors, 2) disruption of forward vesicular traffic between endoplasmic reticulum and Golgi with brefeldin A (BFA, and 3) cellular ATP depletion. Protein synthesis inhibition with cycloheximide for 44 min slowed neither basal nor stretch-augmented ANP secretion but instead accelerated stretch-augmented secretion at low (but not at physiological) external Ca2+ concentration, suggesting that the constitutive component does not contribute substantially to either basal or stretch-augmented secretion. BFA, which disassembled Golgi cisternae, increased the stretch-augmented secretory rate via the regulated pathway and prevented Ca(2+)-dependent inactivation with time. Cellular ATP depletion rapidly and completely inhibited stretch-augmented secretion. We conclude that both basal and stretch-augmented utilize the energy-dependent regulated pathway, drawing on a large reservoir of concentrated prohormone stored in granules that is not detectably depleted during 44 min of stretch-augmented secretion at 37 degrees C.

Animals↗