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Effects of 18 days of bed rest on leg and arm venous properties.

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.

Adolescent↗

Exercise conditioning in middle-aged men after 10 days of bed rest.

Of 12 healthy men with a mean age 50 +/- 4 years who had been at bed rest for 10 days, six were randomly assigned to perform individually prescribed physical exercise daily for 60 days after bed rest (exercise group) and six simply resumed their customary activities (control group). Exercise group subjects were significantly more active than control subjects during this interval (p less than .05). Two classic training effects observed in the 60 days after bed rest were significantly larger among exercise than among control group subjects; compared with values immediately after bed rest, heart rate at a constant submaximal workload declined by 36 +/- 11 beats/min in the exercise group vs 16 +/- 8 beats/min in the control group and peak oxygen consumption increased by 4.8 +/- 4.2 vs 2.2 +/- 5.0 ml/kg/min (both p less than .05). Despite these differences in the cardiovascular response to exercise, peak oxygen consumption in both groups returned to before-bed rest levels by 30 days after bed rest, and this was accompanied by significant (p less than .05) and similar increases in resting left ventricular end-diastolic and stroke volumes in both groups. Simple resumption of usual physical activities after bed rest was as effective as formal exercise conditioning in restoring functional capacity to before-bed rest levels.

Bed Rest↗

Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease.

Coronary vasomotion was studied at rest and during bicycle exercise with biplane quantitative coronary arteriography in 28 patients with coronary artery disease. Patients were divided into two groups; the first 18 patients served as controls (group 1), and the next 10 patients were treated with propranolol 0.1 mg/kg, which was infused intravenously before exercise (group 2). Luminal area of a normal and a stenotic vessel segment was determined at rest, during supine bicycle exercise, and 5 minutes after sublingual administration of 1.6 mg nitroglycerin after exercise. In group 1, the normal vessel showed vasodilation (+16%, p less than 0.001) during exercise, whereas the stenotic vessel segment showed vasoconstriction (-31%, p less than 0.001). After sublingual administration of nitroglycerin, there was coronary vasodilation of both normal (+36%, p less than 0.001 vs. rest) and stenotic (+20%, p less than 0.001) vessel segments. Patients with angina pectoris during supine exercise (n = 10) had significantly (p less than 0.05) more vasoconstriction (-36%) than patients without angina (-23%). In group 2, intravenous administration of propranolol at rest was associated with a decrease in luminal area of both normal (-24%, p less than 0.001) and stenotic (-43%, p less than 0.001) vessel segments; however, during subsequent exercise, both normal (-2%, p = NS vs. rest) and stenotic (-3%, p = NS vs. rest) vessel segments dilated when compared with the measurements after propranolol. Administration of nitroglycerin further increased luminal area of both vessel segments (normal segment, +23%, p less than 0.001; stenotic segment, +46%, p less than 0.001 vs. rest). It is concluded that dynamic exercise in patients with coronary artery disease is associated with coronary vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Patients with exercise-induced angina had significantly more stenosis vasoconstriction than patients without angina although minimal luminal area at rest was similar. Intravenous administration of propranolol is accompanied by a significant decrease in coronary luminal area of both normal and stenotic vessel segments at rest, which is overridden by dynamic exercise and sublingual nitroglycerin. The reduction in myocardial oxygen consumption and the prevention of exercise-induced stenosis vasoconstriction might explain the beneficial effect of beta-blocker treatment in most patients with coronary artery disease.

Adult↗

The significance of resting thallium-201 delayed SPECT for assessing viability of infarcted regions--comparison with exercise thallium-201 SPECT.

To clarify the clinical significance of resting thallium-201 (Tl) delayed SPECT for assessing the viability of infarcted regions, we studied resting Tl initial and delayed Tl SPECT one week after exercise (Ex) Tl SPECT in 38 patients (40 regions) with old myocardial infarction (OMI) and 35 patients (37 regions) with effort angina pectoris (EAP). Analysis of resting Tl and Ex Tl SPECT divided the patients with OMI into 3 groups. Twenty-three patients whose perfusion defect (PD) on resting delayed image was same as that of Ex delayed image were divided into 12 patients with Ex Tl redistribution (RD) (G1) and 11 patients without Ex Tl RD (G3). Fifteen patients showed a decrease of PD on resting delayed image compared with Ex delayed image (G2). Thirty-five patients with EAP were divided into 18 patients who had no PD on Ex delayed image (G1) and 17 patients whose PD did not disappear on Ex delayed image but disappeared on resting delayed image (G2). The increase of pulmonary artery wedge pressure on Ex was higher in G2 than in G1 of both OMI and EAP (OMI; G1 15 +/- 16 mmHg vs G2 27 +/- 7 mmHg; p less than 0.01, EAP; G1 12 +/- 7 mmHg vs G2 22 +/- 6 mmHg; p less than 0.05). The percent Tl uptake of the PD on Ex Tl initial images was lower in G2 than in G1 of both OMI and EAP (OMI: G1 63 +/- 7% vs G2 55 +/- 9%; p less than 0.05, EAP: G1 72 +/- 7% vs G2 65 +/- 9%; p less than 0.05). That of the PD on resting Tl delayed images was higher in G1 and G2 than in G3 of OMI (G1 78 +/- 7%, G2 74 +/- 8%, G3 41 +/- 10%; G1 vs G3, G2 vs G3 p less than 0.001). The prevalence of akinetic or dyskinetic wall motion on left ventriculography was higher in G2 than G1, and in G3 than G2 (G1 24.3%, G2 52.2%, G3 85.7%; p less than 0.001). Thus, in patients with OMI the decrease of Tl PD on resting Tl delayed images compared with Ex delayed images may indicate severe ischemia induced by stress as well as in patients with EAP, and furthermore the presence of viable muscle. On the other hand, the infarcted region without decrease of Tl PD on resting delayed images may lack viable muscle.

Aged↗

Length dependent potentiation and inhibition of post-rest twitch tension development in adult cat and kitten papillary muscles.

If a rest interval is applied to a regularly stimulated cardiac muscle, the first contraction after this interval (post-rest contraction) has either a greater (post-rest potentiation) or a smaller (post-rest inhibition) developed tension than the regular contraction. Positive inotropic interventions will augment the post-rest potentiation and reduce the post-rest inhibition. We examined the effects of muscle stretching on the post-rest contraction in papillary muscles isolated from adult cats and from kittens and compared the effects with those of two typical inotropic interventions: high frequency stimulation and high calcium concentration. We found that muscle stretching augmented the post-rest potentiation and reduced the post-rest inhibition in a manner similar to the two inotropic interventions in the adult cat papillary muscle, and that these effects were consistently reversed in the kitten papillary muscle. The similarity of the effect of muscle stretching to those of the two typical inotropic interventions in either adult cat or kitten papillary muscle suggests that the effect of muscle stretching is due to an inotropic effect of muscle length change.

Animals↗

Determining the resting position of the glenohumeral joint: a cadaver study.

STUDY DESIGN: Single-session repeated-measures design. OBJECTIVE: To define the resting position of the glenohumeral joint by investigating the magnitude of the anterior and posterior displacements of the humeral head and medial and lateral rotation ranges of motion (ROMs) of the glenohumeral joint at different abduction angles in cadaver specimens. BACKGROUND AND PURPOSE: The resting position of a joint is the position in the joint's ROM at which the joint capsule has its greatest laxity. It is frequently chosen as the position for assessing and treating joints with dysfunction. However, no study has been conducted to determine the resting position of the glenohumeral joint. METHODS: Seven freshly frozen cadaver shoulder specimens (age at time of death [mean +/- SD] was 66.9 +/- 2.5 years) were studied. Specimens were mounted on a system that uses computer-controlled hydraulics and motors to induce and monitor translation and rotation movements of the glenohumeral joint. The magnitudes of total displacement (DTotal) of the head of the humerus and total ROM (RTotal) of the glenohumeral joint were measured in the plane of the scapula at 0 degrees (neutral), 30 degrees, 40 degrees, 50 degrees, 60 degrees, and the end range of glenohumeral joint abduction. The resting position was determined as the midpoint of the shared range of the 95% to 99.9% confidence intervals of the predicted abduction position where the peaks of displacement and rotation occurred. RESULTS: The DTotal measurements (mean +/- SD) at 0 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, and the end range of glenohumeral joint abduction were 30.53 +/- 9.35, 44.87 +/- 7.34, 45.35 +/- 8.53, 43.99 +/- 10.02, 39.63 +/- 9.85, and 23.80 +/- 10.42 mm, respectively. The RTotal measurements (mean +/- SD) for the same positions were 67.15 degrees +/- 15.87 degrees, 95.64 degrees +/- 24.26 degrees, 98.88 degrees +/- 29.56 degrees, 97.08 degrees +/- 30.17 degrees, 90.91 degrees +/- 28.73 degrees, and 63.48 degrees +/- 25.93 degrees, respectively. The resting position was located at 39.33 degrees +/- 4.37 degrees of glenohumeral abduction (45.13% +/- 7.58% of the available abduction ROM). The resting position (Y) varied linearly with the maximum available abduction ROM (X) (Y = 0.607X - 13.120, R2 = 0.679, F = 10.61, P = 0.023). There was a main effect of joint position on both displacement (P<0.001) and rotation ROM (P<0.001). CONCLUSION: In the plane of the scapula, the resting position of the glenohumeral joint (angle measured between the scapula and humerus) occurred at 39 degrees of abduction (45% of the maximum available abduction ROM) and varied linearly with the amount of available abduction ROM. This finding suggests that in patients with glenohumeral joint hypomobility the resting position is located closer to neutral and that evaluation and treatment should be initiated accordingly at a smaller angle of abduction than the traditional resting position. Our data were derived from cadaver specimens, therefore, caution should be taken when generalizing the results of the present study to a patient population.

Aged↗

Body temperature and skin blood flow during a 14-day bed-rest in a head-down tilt position in humans.

Exposure to microgravity or simulated microgravity is known to affect regulatory function in autonomic nervous system. With regard to thermoregulation, simulated microgravity impairs sweating and induces lower skin and higher internal temperatures during physical work. During supine rest after HDT bed rest, the internal temperatures were reported to be higher than those of pre-HDT bed rest in some studies but not in others. There is no report about the dynamic changes of skin blood flow during 14-day HDT bed rest. The process of HDT bed-rest deconditioning on the function of the thermoregulatory system is virtually unknown. The HDT induces an immediate cephalad fluid shift which would inhibit the sympathetic outflow through the arterial and cardiopulmonary baroreflexes, which may increase the skin blood flow. On the other hand, prolonged HDT bed rest induces dehydration, which will increase sympathetic outflow through cardiopulmonary baroreceptor modulation. Both sympathetic activation and dehydration itself will decrease skin blood flow. It seems probable that the general effect on skin blood flow may reverse along the HDT bed rest. However, the dynamic characters of skin blood flow and body temperature during the HDT bed rest have not been studied thoroughly. Therefore, the purpose of present study was to investigate the changes of skin blood flow and body temperature during 14 days HDT bed rest.

Adult↗

Effects of acute exercise on attenuated vagal baroreflex function during bed rest.

We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 degrees head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally-mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4% (p < 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p < 0.05) by 10.7 +/- 3.7% above pre-bed rest levels and 34.3 +/- 7.9% above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise.

Adult↗

The effects of rest interval length and training on quadriceps femoris muscle. Part I: knee extensor torque and muscle fatigue.

AIM: The purpose of this study was to examine the effects of rest interval on quadriceps femoris (QF) muscle strength and fatigue during short-term, high-intensity training. METHODS: Fifteen healthy males were assessed for isokinetic QF strength, via peak torque (PT), work (WK) and power (PW), at a pre-set angular velocity of 180 deg x s(-1). Quadriceps femoris muscle fatigue was evaluated as the decline in isokinetic work and power (slope) across 30 maximal concentric contractions. Subjects were randomly assigned to 1 of 3 groups: Group 1 (short rest interval), Group 2 (long rest interval), and Group 3 (control-no training). Subjects in Group 1 received a rest period of 40 s in between exercise sets corresponding to a 2:1 rest:work ratio. Subjects in Group 2 received a rest period of 160 s corresponding to an 8:1 rest:work ratio. Groups 1 and 2 performed isokinetic knee extension contractions at 180 deg x s(-1) 2 days per week for 6 weeks. RESULTS: The results demonstrated a significant increase in QF muscle PT across the 6 week training period in the long rest interval group, and no significant changes in the short rest interval and control groups. Quadriceps femoris muscle work and power were observed to not change significantly across the training period in all 3 groups. The reduction in QF muscle work across the single set of 30 repetitions was observed to decrease significantly in the control group across the 6 week duration; no other significant changes in QF muscle fatigue for work and power were observed. CONCLUSION: The major findings of this study suggests that the possibility of different physiological mechanisms of adaptation exist for QF muscle peak torque, work and power, while changes in muscle fatigue resistance may be present when assessed across multiple, rather than a single, bouts of activity.

Adaptation, Physiological↗

Cancellous bone structure of iliac crest biopsies following 370 days of head-down bed rest.

INTRODUCTION: Static bone histomorphometry was applied to existing iliac bone sections originating from a 370-d 5 degrees head-down bed rest experiment. This bed rest experiment is the longest ever to have been conducted. We hypothesized that bed rest would decrease cancellous bone volume fraction and that this effect would be reversed by countermeasures. METHODS: Eight healthy male subjects underwent 370 d of 5 degrees head-down bed rest. Three subjects were treated with bisphosphonate (Xidifon, potassium salt of ethane-1-hydroxy-1-disphosphonate, EHDP) combined with an exercise regimen (1-2 h x d(-1)) for the entire study period. Five subjects underwent 120 d of bed rest without countermeasures followed by 250 d of bed rest with the exercise regimen. Transiliac bone biopsies were obtained either at baseline and day 366, or at baseline, day 116, and day 366 at alternating sides of the ileum. Static histomorphometry was performed using a computerized method. RESULTS: The 120 d of head-down bed rest without countermeasures resulted in decreased bone volume fraction BV/TV (-6.3%, p = 0.046) and trabecular number (Tb.N; -10.2%, p = 0.080) and increased trabecular separation (Tb.Sp; 14.7%, p = 0.020), whereas the 250 d of subsequent head-down bed rest with exercise treatment prevented further significant deterioration of the histomorphometric measures. DISCUSSION: The 120 d of 5 degrees head-down bed rest without countermeasures induced significant deterioration of iliac crest cancellous bone histomorphometric properties. On average, the countermeasures consisting of either bisphosphonate and exercise, or exercise alone were able to either prevent or stop immobilization-induced changes of the iliac cancellous bone structure.

Adult↗

[Relation of the difference between blood pressure before and after 5 minutes' rest to blood pressure status one year later in an epidemiological setting].

The relationship of the difference between blood pressures before and after 5 minutes' rest (before minus after) to resting blood pressures one year later was studied on 439 subjects, aged 35 to 44 years, not being treated for hypertension, in an epidemiological setting. Multiple regression analysis was applied to systolic (SBP) and diastolic blood pressure (DBP) separately. Both the resting SBP level and the SBP difference were significant predictors of the resting SBP one year later in both sexes. For resting DBP one year later, the resting DBP level and DBP difference were found to be significant in females. Multiple logistic analysis was used to identify the factors which predict development from normotension to above borderline hypertension one year later. The SBP difference as well as the resting DBP level were significant predictors in males. These findings suggest that BP difference between before and after 5 minutes' rest may be an important indicator of subsequent BP status, and therefore there would be value in measuring blood pressure before as well as after rest with particular attention to BP difference.

Adult↗

[Usefulness of rest-redistribution on thallium myocardial scintigraphy in patients with acute myocardial infarction by SPECT: analysis by bull's eye and unfolded map images].

The purpose of this study was to clarify the clinical significance of rest-redistribution in myocardial scintigraphy (SPECT) in acute myocardial infarction (AMI). Thirty patients with AMI within one week after the onset of attack were studied. SPECT images were obtained 10 min and three hours after injection of 201Tl. Bull's eye images and unfolded map images were prepared. A 201Tl uptake was studied at the infarct and non-infarct sites. Exercise SPECT and radionuclide angiography (RNA) were performed in all patients one month after the onset of AMI, and the findings were compared with clinical and coronary angiographic (CAG) findings. 1. Redistribution of thallium at rest was observed at the infarct sites in nine of the 30 patients. 2. Redistribution at rest was observed at the non-infarct sites in eight patients. 3. Redistribution at rest was observed during exercise SPECT one month after the onset of AMI in patients with redistribution at rest in the acute phase. 4. In patients with redistribution at rest at the infarct site, left ventricular ejection fraction (EF) improved one month after the onset of AMI (delta EF greater than 5%), but it decreased slightly during exercise. 5. Wall motion at the infarct site was not much impaired in patients who showed redistribution at rest at the infarct site. 6. Angina pectoris and recurrence of myocardial infarction were observed more frequently in those with redistribution at rest on SPECT. 7. No characteristic findings were obtained on CAG in those with redistribution at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The hemodynamic effects of repeated bed rest exposure.

Hemodynamic changes were measured during stepwise exposure to lower-body negative pressure (LBNP) (5 min, -20, -30, and -40 mm Hg) in a group of seven physically active subjects before and after consecutive exposure to three 2-week bed rest periods. Bed rest exposures were separated by 3-week periods of ambulatory recovery. Dynamic exercise (68% max O2, 30 min each day) and isometric exercise (21% max leg extension, 30 min each day) performed during bed rest and reambulation failed to prevent deconditioning or accelerate the recovery process between bed rest exposures. Heart rate (HR) and end-diastolic volume index (EDVI) proved to be parameters showing greatest changes during LBNP. Heart rate increases at -40 mm Hg LBNP (compared to respective pre-LBNP levels) were 13.3%, 35.1%, and 51.0% for each of the pre-bed rest exposures, while respective changes after bed rest were 57.8%, 57.2%, and 75.5%. The significantly elevated HR responses during subsequent pre-bed rest (control) periods indicated incomplete recovery despite mild exercise and ambulation. Comparison of EDVI and HR revealed a similar linear regression relationship during LBNP before and after bed rest so that EDVI = 112.5-0.85 x HR, r = -0.97. We conclude from these findings that cardiovascular deconditioning for physically active individuals involves factors other than simple loss of plasma volume, requires at least 3 weeks or longer to return to the pre-bed rest state, and is not counteracted by the levels of aerobic and/or isometric exercise used in the present study.

Adult↗

Does 48 hours' bed rest influence the outcome of acute low back pain?

BACKGROUND: Bed rest is a traditional treatment for back pain, yet only in recent years has the therapeutic benefit of this been questioned. AIM: The aim of this pilot study was to ascertain whether or not 48 hours' bed rest had an effect on the outcome of acute low back pain. METHOD: The study was conducted as a randomized controlled trial to compare a prescription of 48 hours' strict bed rest with controls; the control subjects were encouraged to remain mobile and to have no daytime rest. Nine general practitioners from practices in the West Midlands recruited patients in the age range 16-60 years who presented with low back pain of less than seven days' duration, with or without pain radiation. The outcome measures assessed were: change in straight leg raise and lumbar flexion after seven days, Oswestry and Roland-Morris disability scores after seven days and 28 days, and time taken from work. RESULTS: Forty two patients were recruited: 20 were allocated to bed rest and 22 as controls. Compared with the bed rest group the control group had statistically better Roland-Morris scores at day seven (P < 0.05) but not at day 28. At day seven, there were no statistically significant differences between groups in straight leg raise or lumbar flexion measurements although the control group had a better mean lumbar flexion than the bed rest group. The improvement in disability scores at day seven compared with day one was similar for the two groups but more of the control group had fully recovered (defined as scores of one or zero on the Roland-Morris disability scale and five or less on the Oswestry disability scale) by day seven. Remaining mobile did not appear to cause any adverse effects. The number of days lost from work in both groups was equal. A large number of self-remedies and physical therapies were recorded by subjects from both groups. CONCLUSION: The results of this pilot study did not indicate whether bed rest or remaining mobile was superior for the treatment of acute low back pain; however, the study sample was small. Subjects in the control group possibly fared better as they appeared to have better lumbar flexion at day seven. It appears that 48 hours' bed rest cannot be recommended for the treatment of acute low back pain on the basis of this small study. Large-scale definitive trials are required to detect clinically significant differences.

Acute Disease↗

Orthostatic tolerance and autonomous nervous functions before and after 20-days bed rest.

To determine the critical factor that induces tachycardia during orthostasis after bed rest, we tested some autonomous nervous functions and the reaction to lower body negative pressure before and after 20 days horizontal bed rest. Subjects were 5 young healthy males and one female. Carotid vagal baroreflex sensitivity was evaluated by cardiac response to a gradual increase in carotid distending pressure of 150 mmHg within 10 s by neck suction after neck positive pressure. Combined effects of cardiopulmonary and aortic baroreflexes were assessed by the cardiovascular responses during Valsalva manoeuvre. Sympathetic reactivity was evaluated by a cold pressor test. The carotid vagal baroreflex tended to be diminished after bed rest in supine rest, but unchanged in seated position. Cardiac responses to Valsalva manoeuvre did not change after bed rest, although blood pressures decreased more during the manoeuvre after bed rest. Cold pressor response did not change after bed rest. Heart rate response during lower body negative pressure was increased after bed rest. In conclusion, combining our results from several autonomous nervous functions suggested that the exaggerated orthostatic tachycardia after bed rest could not be explained by the changes in sensitivity of carotid, aortic, and cardiopulmonary reflexes and sympathetic reactivity to cold stress.

Adult↗

Mechanisms by which accessory cells contribute in growth of resting T lymphocytes initiated by OKT3 antibody.

This study was undertaken to determine how accessory cells (AC) participate in growth of normal resting T cells initiated by anti-T3 monoclonal antibodies. Highly purified peripheral blood resting T cells were obtained by sequentially using three procedures (adherence to plastic surface, adherence to nylon wool columns and treatment with four monoclonal antibodies against antigens on AC and activated T cells plus complement). The assays for T cell growth were carried out at low cell density (10(4) cells/well) and with T cell populations where we could not detect cells bearing OKM1 and Ia antigens. Soluble OKT3 antibody, concanavalin A, recombinant interleukin 2 (IL 2) or purified interleukin 1 (IL 1) alone did not induce proliferation of purified resting T cells. Recombinant IL2 together with soluble OKT3 antibody stimulated significant growth whereas purified IL1 and two distinct preparations derived from AC containing IL 1 activity did not. Nevertheless, purified IL 1 amplified the proliferation of T cells induced by soluble OKT3 antibody in the presence of a small number of irradiated AC (3%). Phorbol myristate acetate (PMA) together with soluble OKT3 antibody activated purified resting T cells to proliferate, but PMA alone had little growth-promoting activity only. Soluble OKT3 antibody did not by itself induce a detectable number of resting T cells to express receptors for IL2 as determined by direct immunofluorescence staining and FACS analysis with monoclonal anti-IL2 receptor antibody. Cloned IL2 or purified IL1 alone did not induce resting normal T cells to express receptors for IL2 either. In contrast, T cells exposed to both soluble OKT3 antibody and IL2 exhibited IL2 receptors. PMA alone stimulated some resting T cells to express IL2 receptors and this response was significantly increased when the drug was used together with soluble OKT3 antibody. Studies were performed with unfractionated mononuclear cells from a donor whose cells respond to OKT3 (IgG2) but not to Leu 4 (IgG1) anti-T3 antibodies. Recombinant IL 2 but not purified IL 1 corrected the defective response to Leu 4 antibody. Finally, OKT3 antibody linked to beads, but not in soluble form, and purified IL1 replaced AC in growth of purified resting T cells. Based on these data I conclude the following: (a) AC participate in growth of resting normal T cells initiated by anti-T3 antibodies through their Fc receptors in two ways, namely, by providing a matrix to favour cross-linking of the T3 complex and simultaneously by secreting IL1.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Possible functional linkage between the cardiac dihydropyridine and ryanodine receptor: acceleration of rest decay by Bay K 8644.

The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal ICa trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or ICa. To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Regulation of endothelin-1 at rest and during a short steady-state exercise in 21 COPD patients.

Endothelin-1 (ET-1) is a vasoconstrictive peptide which may play a relevant role in the pathogenesis of pulmonary hypertension (PH) in COPD patients. We assessed the correlations of plasmatic ET-1 levels with pulmonary function data, arterial blood gases and pulmonary haemodynamics in 21 COPD patients with moderate to severe airway obstruction (FEV1: 1.19+/-0.49 l, mean+/-SD). There were 11 hypoxemic patients (PaO2 <65 mmHg). Six patients had resting PH (mean pulmonary artery pressure >/=20 mmHg). Eight patients had exercising PH (PAP >/=30 mmHg) during a short (6 min) 30 W steady state exercise. At rest, arterial ET-1 levels were significantly higher in COPD patients with hypoxemia when compared to those without hypoxemia (16.6+/-2.7 vs. 12.5+/-3.9 pM/l, P=0.02) and in COPD patients with PH when compared to those without PH (16.5+/-3.4 vs. 13+/-3.9 pM/l, P=0.04). Resting arterial ET-1 levels were negatively correlated with PaO2 (r=-0.45, P=0.05). At rest, the differences between mixed venous and arterial ET-1 levels were positively correlated with FEV1 (r=0.54, P=0.024). At exercise, the mean arterial ET-1 level was not significantly different from the mean resting ET-1 level (13.8+/-3.4 vs. 13.3+/-4 p M/l, NS). There were eight COPD patients who had decreasing arterial ET-1 levels between rest and the end of a 6 min exercise, and six COPD patients who had increasing arterial ET-1 levels. These variations of arterial systemic ET-1 levels from rest to exercise were negatively correlated with FEV1 (r=-0.66, P=0.01). We conclude that in COPD patients (1) at rest, arterial ET-1 levels are increased in hypoxemia or pulmonary hypertension and (2) at rest or during exercise, the turn-over of ET-1 may be dependent of the degree of the bronchial obstruction.

Aged↗