Donor and recipient characteristics that influence functional capacity of heart transplant recipients.
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Biomedical subjects
Publications and source records attributed to M Rieu.
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The aim of our study was to find out, which are the thyroid linked mechanisms responsible for the changes in myosin isoform composition which accompany endurance training (ET) in rodents. We studied the interaction between ET and altered sedentary group with no thyroid treatment or Se group. Six groups of rats were compared: (1) a trained group with no thyroid treatment or T group; (2) a thyroid state in rats; (3) a sedentary group rendered hypothyroid with 6-n-propyl thio uracil (H); (4) a sedentary group rendered hyperthyroid with T3 (150 microg kg(-1) every other day for 4 weeks) (St); (5) trained rats rendered hyperthyroid with T3 (150 microg kg(-1) every other day for 4 weeks) (Tt) and (6) a trained group kept euthyroid with T3 (150 ng kg(-1) every other day for 4 weeks) (Te). In each group myosin isoform composition was determined in five muscles, three locomotor muscles: (1) extensor digitorum longus, (2) superficial lateral gastrocnemius, (3) deep medial gastrocnemius, (4) an antigravity muscle, the soleus and (5) a rhytmic respiratory muscle, the crural diaphragm. Different muscles responded in a specific way to variations of the thyroid state and training.
The aim of this study was to quantify modifications in the expression of skeletal myosin light chain (MLC) and myosin heavy chain (MHC) isoforms of five muscles, according to their fiber composition and function, following endurance training in rats. Rodents were assigned randomly to one of two groups: caged sedentary controls (C) or endurance-trained rats (T). In T rats, three out of the four fast and mixed muscles studied exhibited a significant increase in the expression of MLC1s, 1f and 2s and a significant decrease in MLC2f and 3f, the exception being the plantaris muscle. In two out of the four muscles we observed a significant increase in MHCI and IIa, the exception being both gastrocnemii, where the expression of MHCI did not change. In the soleus of T rats, the expression of MLC1s, 2f and 3f decreased significantly, while that of MLC2s increased significantly, compared with those of C rats. The expression of MHCIIa in T rats decreased significantly compared with that of C rats, while the expression of MHCI increased significantly. In all muscles studied, a significant slowing of myosin isoforms was observed after endurance training.
BACKGROUND: This study was designed to study the effect of an exhausting exercise test on plasma lipid peroxidation marker (malondialdehyde, MDA) and on vitamin E levels in hemodialyzed patients (HD) compared to healthy control subjects (HC). METHODS: Eight sedentary chronically HD, (39.0+/-10.8 years) and eight sedentary HC (38.4+/-12.4 years) were studied. Before exercise, the activity of scavenger enzymes [plasma and erythrocyte glutathione peroxidase (GPX), and erythrocyte superoxide dismutase (SOD)] was determined. All subjects performed a symptom-limited exercise test; respiratory gas exchanges were collected on-line and blood was sampled five min before exercise, at exhaustion and after 30 min of recovery. RESULTS: At rest, the activity of plasma and erythrocyte GPX and erythrocyte SOD was significantly lower in HD than in HC. Exercise provoked an increase of plasma MDA concentration after recovery in HD patients, whereas our HC group show a decrease in MDA plasma level immediately after exercise, returning to the rest values during recovery. Exercise induced no change of vitamin E concentration in HD whereas in HC it increased during recovery. CONCLUSIONS: Our results indicate that: 1) at rest: although hemodialyzed patients showed lower scavenger enzymes activity than HC subjects, there was no difference in MDA plasma level between groups; 2) there is some evidence that physical exercise contribute to oxidative stress during recovery in HD patients, and 3) exercise induced an increase in plasma vitamin E concentration in healthy subjects.
Lactate transport was investigated in newborn rat muscle cells in culture. The aim was to study the lactate transport function at two stages of cell differentiation in culture: (i) during the proliferative phase characterized by myoblasts and myotubes (MyB/MyT2) obtained after 2-3 seedings, (ii) when myotubes (MyT1) grow old in culture after 8-9 seedings. In both developmental stages MyB/MyT2, lactate was carried following a saturable and sigmoidal velocity curve: the Hill and the Scatchard plot analyses confirmed an allosteric or multisite mechanism of lactate transport with two classes of carriers: one of low and one of high affinity i.e., 8.6 and 0.95 mm, respectively, which are associated with high and low transport capacities (V(m)) i.e., 9.1 and 0.67 nm/min/mg, respectively. With MyT1, the velocity curve of lactate transport presented a hyperbolic profile, and the Hill plot analysis gave a Hill number near one suggesting that for cell aging in culture the decrease in cooperativity shows that lactate transport essentially occurs through the low affinity transport system. Inhibitor effects also contributed to evidence for at least two systems of transport. Results obtained from primary cells give evidence for the early activity of lactate transport system at the Myb/MyT2 stage and its evolution during cell aging in culture (MyT1). Sarcolemmal lactate transport in primary cultures of myocytes is accomplished by multiple carriers, neither of which are MCT1 or MCT2 as confirmed by immunoblots.
PURPOSE: The objectives of this study were twofold: 1) to determine the effect of incremental exercise to volitional fatigue on plasma levels of lipid peroxidation (malondialdehyde) in heart transplant recipients (HRT) and 2) to examine blood antioxidant capacity in HTR by assessment of antioxidant enzyme activities and vitamin E levels. METHODS: Seven endurance-trained HTR (mean +/- SD; age 39.7 +/- 12.8 yr) and seven endurance-trained healthy, age-matched control subjects (HC) (mean age 40.6 +/- 10.7 yr) performed a symptom-limited incremental exercise test on a cycle ergometer. Venous blood samples were obtained at rest, exercise, and during recovery and analyzed for plasma levels of malondialdehyde (MDA) as well as markers of blood antioxidant capacity. After exercise and during recovery, all dependent measures were corrected for plasma volume changes induced by exercise. Significance was established at (P < 0.05). RESULTS: No group differences existed in plasma levels of MDA at rest. Further, graded exercise did not alter plasma levels of MDA in either group. Resting erythrocyte glutathione peroxidase (GPX) activity was significantly lower and erythrocyte superoxide dismutase (SOD) activity was higher in HTR compared with HC. Finally, at rest, no group differences existed in plasma GPX activity or vitamin E levels. CONCLUSIONS: Graded exercise to fatigue does not promote an increase in oxidative stress in blood of exercise trained HTR. Therefore, physical exercise does not appear to pose an oxidative-stress risk for these patients.
OBJECTIVES: The purpose of this study was to show that the chronotropic potential of the well trained heart transplant recipient (HTR) does not limit exercise capacity. BACKGROUND: Chronotropic incompetence is considered to be the main limiting factor of the functional capacity of heart transplant recipients. However, no systematic study had been published on patients who had spontaneously undergone heavy endurance training for several years. METHODS: Heart rate (HR) and respiratory gas exchanges (VO2, VCO2, VE) were measured in 14 trained HTRs (T-HTRs) during exercise tests on a bicycle, on a treadmill and by Holter electrocardiography during a race. RESULTS: Peak values observed in T-HTRs during the treadmill test were higher than those reached during the bicycle test (VO2peak: 39.8+/-6.9 vs. 32.5+/-7.8 ml x kg(-1) x min(-1), p < 0.001; HRpeak: 169+/-14 vs. 159+/-16 bpm, p < 0.01). During treadmill exercise VO2peak and HRpeak values observed were very close to the mean predicted VO2pmax and HRpmax. The maximum heart rate during the race (HRrace) was greater than HRpeak values during the treadmill test (179+/-14 vs 169+/-14 bpm, p < 0.01) and slightly above the mean predicted values (HRrace/HRpmax X 100 = 101+/-10%). The treadmill exercise test yields more reliable data than does the bicycle test. CONCLUSIONS: Extensive endurance training enables heart transplant recipients to reach physical fitness levels similar to those of normal sedentary subjects; heart rate does not limit their exercise capacity.
We have examined the effect of male sexual hormones on the regeneration of skeletal muscles. Degeneration/regeneration of the left soleus and extensor digitorum longus muscles (EDL) of Wistar male rats was induced by an injection of snake venom (2 microg, Notechis scutatus scutatus). During the muscle regeneration (25 days), rats were treated with either oil (CON), nandrolone (NAN), NAN combined with exercise (NAN + EXE) or were castrated (CAS). Muscle growth and myosin heavy chain (MyHC) isoform content of regenerating muscles were studied. Castration altered the concentrations of MyHC in venom-treated EDL (P < 0.01) and soleus (P < 0.05). NAN increased the mass (P < 0.01) of regenerating soleus and decreased the relative amount of fast MyHC protein (% of total, P < 0.05). The effect of NAN + EXE on the fast MyHC proteins of venom-treated soleus was opposite (P < 0.05). NAN and NAN + EXE were without effect on the regenerating EDL (P > 0.05). In conclusion, it is possible that male sexual hormones play a role in the growth (synthesis of contractile proteins) of regenerating muscles in rat. In addition, contrary to NAN + EXE, NAN could be beneficial to soleus regeneration.
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Membrane lactate transport was studied in skeletal muscle cells and membrane vesicles from the L6 line in relation to in vitro myogenesis. In myoblasts, lactate was transported by simple diffusion and insensitive to classical inhibitors: a positive correlation between onset of creatine kinase activity and lactate transport in differentiated myotubes was observed and could be considered to be a functional marker of cell differentiation. In myotubes, complete analysis of the velocity curves (direct coordinates, Eadie-Scatchard plots, Hill plots) gave parameters showing that lactate was carried by an allosteric or multisite system. This was confirmed by using sarcolemmal vesicles and specific inhibitors. In whole cells, alpha-cyano-4-hydroxycinnamic acid (CIN) and parachloromercuribenzylsulphonic acid (pCMBS) inhibited the maximal velocity without modifying the global cooperativity of the system. The weak effect of 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), which has a low affinity constant (Ki = 22.5 microM), implicated the monocarboxylate system rather than the anionic exchanger as a carrier system in muscle cells. CIN and DIDS exhibited one type of interaction with lactate carriers, and the curvilinear shape of the lactate Hill plot with or without inhibitors suggested that inhibitors were active at the same family of interaction sites and had a common range of affinities. The apparent competitive inhibition of pyruvate (Ki = 3.2 mM) did not modify the transport pathway of lactate in L6 myotubes. In conclusion, kinetic analysis of lactate transport in the presence or absence of inhibitors gave evidence for a multisite lactate carrier activity in myotubes composed of two systems at least, related to two or three isoforms of lactate carriers.
It is well known that normal and mildly elevated luteinizing hormone (LH) levels induce increased activity of ovarian 17-hydroxylase and 17,20-lyase, the cytochrome P450cl7alpha (P450) enzymes. This leads to increased ovarian 17alpha-hydroxyprogesterone (17-OHP) and androstenedione production. In contrast, it has been shown in both in vitro and in vivo studies in animals and in in vitro studies in women that high LH concentrations have opposite effects on these enzymes. These LH down-regulating effects appear to be more marked on 17,20-lyase than on 17-hydroxylase. Finally, these LH effects have not been reported in vivo in women. Therefore, we investigated the relationships between serum LH levels and serum 17-OHP and androstenedione concentrations in 263 consecutive hirsute women (HW) with normal serum 17-OHP responses to acute adrenocorticotropin (ACTH) stimulation. The patterns of basal serum steroid concentrations differed according to the basal serum LH levels. Indeed, for relationships between LH and 17-OHP concentrations, a positive correlation (P < 0.001) was found between the levels of these parameters when LH levels ranged from 0.2 to 9.0 IU/l. Conversely, for LH levels greater than 9.0 to 21.0 IU/l, LH values were negatively correlated (P<0.001) with 17-OHP concentrations. Similar results were observed for relationships between LH and androstenedione levels but the LH peak level related to decreasing androstenedione concentrations was 12.0 IU/l. Finally, the mean 17-OHP level in patients with LH levels which induced marked P450 down-regulation (i.e. more than 12 IU/l) was similar to that in patients with LH levels within the normal range (i.e. less than 6 IU/l). In contrast, the mean androstenedione level in the former patients was markedly higher (P<0.001) than that in the latter patients. In conclusion, as previously reported in in vitro studies, this in vivo study indicates that LH induces stimulating and down-regulating effects on both ovarian delta(4)17-hydroxylase and delta(4)17,20-lyase activities as serum LH levels gradually increase. However, in contrast to in vitro studies, LH levels which induce P450 down-regulation appear to be less effective on delta(4)17,20-lyase than on delta(4)17-hydroxylase in HW. This strongly suggests that serum factors induce, in most HW, a marked increase in delta(4)17,20-lyase, but not in delta(4)17-hydroxylase, activity leading to both partial impairment of LH-induced delta(4)17,20-lyase down-regulation and complete LH-induced delta(4)17-hydroxylase down-regulation in these patients.
Our purpose was to determine the effect of physical exercise on growth and differentiation during regeneration of a slow-twitch muscle. Degeneration/regeneration of the left soleus muscles of Wistar female rats was induced by injection of a snake venom. Muscular differentiation was studied by monitoring the sequential expression of the various myosin heavy chain isoforms (MHCs). Rats were assigned to one of two groups: cage sedentary (n = 14) or exercised (n = 16). The exercise programme began 1-day post-injection and the rats ran 1 h/day on a motorized treadmill. Then, 9 and 25 days after venom treatment, the soleus MHC phenotype as determined by immunohistology, electrophoresis and immunoblotting, was studied. At 25 days the expression of MHCs by regenerating soleus was not changed by the increased level of physical activity (P > 0.05). Exercised and sedentary regenerating muscles contained similar numbers of type-I fibres (100% of total fibres), levels of MHC-1 (85.4 and 89.5% of total MHCs), MHC-2a and M/HC-2x/d and their fibres expressed MHC-1 (100% of total fibres) and MHC-2 (45-50%) in the same way. Moreover, the masses of regenerating and nonregenerating soleus were significantly increased by physical exercise (P < 0.02). At 9 days no effect of muscular exercise was found. In conclusion, endurance exercise did not alter differentiation of regenerating soleus. Moreover regenerating soleus can respond to increased physical activity by enhancing its mass in the same way as mature muscle.
Although primary muscle cells have been used as intracerebral vehicles for transgene expression in the past, data concerning their long-term survival after grafting into the brain, and the reaction of the host tissue to their implantation are lacking. In order to study these aspects, we have implanted, into the brain, primary muscle cells infected ex vivo with recombinant retroviruses carrying the E. coli LacZ gene. The muscle cells were delivered stereotaxically into different areas of the brain of adult rats and the grafts were analyzed up to 105 days after implantation. Intraventricular implantations did not lead to surviving grafts. In contrast, myoblasts developed when they were grafted into gray or white matter regions. They appeared numerous during the first weeks, but decreased dramatically in number over time. Over months, the grafts appeared to fill up with collagen. Astrocytes elaborated a continuous glia limitans surrounding the implant. Blood vessels coming from the host tissue were found within the grafts. The blood-brain barrier was permanently disrupted within the transplants. beta-Galactosidase activity was abundant during the first weeks, but decreased to a very low level subsequently. This decrease paralleled that of the number of muscle cells. In conclusion, myoblasts transplanted into the adult brain survived only temporarily, which implies a transient transgene expression. In addition, before being eliminated, muscle cells were surrounded by a glia limitans, which may limit exchanges with the host tissue. Altogether, these results suggest that intracerebral transplantation of myoblasts may possibly provide a relevant vehicle only for short-term delivery of a gene product.
Metabolic and cardiovascular adjustments to various submaximal exercises were evaluated in 82 heart transplant recipients (HTR) and in 35 control subjects (C). HTR were tested 21.5 +/- 25.3 (SD) mo (range 1.0-137.1 mo) posttransplantation. Three protocols were used: protocol A consisted of 5 min of rectangular 50-W load repeated twice, 5 min apart [5 min rest, 5 min 50 W (Ex 1), 5 min recovery, 5 min 50 W (Ex 2)]; protocol B consisted of 5 min of rectangular load at 25, 50, or 75 W; protocol C consisted of 15 min of rectangular load at 25 W. Breath-by-breath pulmonary ventilation (VE), O2 uptake (VO2), and CO2 output (VCO2) were determined. During protocol A, beat-by-beat cardiac output (Q) was estimated by impedance cardiography. The half times (t1/2) of the on- and off-kinetics of the variables were calculated. In all protocols, t1/2 values for VO2 on-, VE on-, and VCO2 on-kinetics were higher (i.e., the kinetics were slower) in HTR than in C, independently of workload and of the time post-transplantation. Also, t1/2 Q on- was higher in HTR than in C. In protocol A, no significant difference of t1/2 VO2 on- was observed in HTR between Ex 1 (48 +/- 9 s) and Ex 2 (46 +/- 8 s), whereas t1/2 Q on- was higher during Ex 1 (55 +/- 24 s) than during Ex 2 (47 +/- 15 s). In all protocols and for all variables, the t1/2 off-values were higher in HTR than in C, In protocol C, no differences of steady-state VE, VO2, and VCO2 were observed in both groups between 5, 10, and 15 min of exercise. We conclude that 1) in HTR, a "priming" exercise, while effective in speeding up the adjustment of convective O2 flow to muscle fibers during a second on-transition, did not affect the VO2 on-kinetics, suggesting that the slower VO2 on- in HTR was attributable to peripheral (muscular) factors; 2) the dissociation between Q on- and VO2 on-kinetics in HTR indicates that an inertia of muscle metabolic machinery is the main factor dictating the VO2 on-kinetics; and 3) the VO2 off-kinetics was slower in HTR than in C, indicating a greater alactic O2 deficit in HTR and, therefore, a sluggish muscle VO2 adjustment.
Serotonin (5-HT) stimulates aldosterone secretion in man through activation of 5-HT4 receptors coupled to adenylyl cyclase via a Gs regulatory protein. In adrenocortical cells, the levels of expression of the Gs protein and ACTH receptor are decreased when the cells are deprived of ACTH and angiotensin II (ANG II). In order to examine the possible influence of ACTH and ANG II on the responsiveness of human glomerulosa cells to 5-HT, we have investigated the effect of cisapride, a 5-HT4 receptor agonist, on plasma aldosterone in patients with suppressed plasma ACTH, i.e. patients with corticotropic insufficiency (CI), and in patients with suppressed renin-ANG II activity, i.e. patients with primary hyperaldosteronism (PH) including both aldosterone-producing adenoma and idiopathic hyperaldosteronism. After 2 h of recumbency, all patients received a single oral dose of 10 mg cisapride. In the CI group, cisapride induced a 5-fold increase in plasma aldosterone levels without any modification of plasma renin, potassium or cortisol levels. Combined administration of cisapride and ACTH caused an increase in plasma aldosterone similar to that produced by ACTH alone. In the PH group, cisapride was still able to cause a 3.6-fold increase in plasma aldosterone levels while renin remained suppressed throughout the study. Taken together, these data show that cisapride stimulates aldosterone secretion in CI and PH patients, indicating that prolonged suppression of plasma ACTH or renin-ANG II activity does not affect the sensitivity of glomerulosa cells to 5-HT. The present study also demonstrates that the stimulatory effects of 5-HT and ACTH on aldosterone secretion are not additive.
Experiments utilizing reaction time to measure the effects of fatigue on cognition must discern sensitivity of peripheral and central processing to strenuous exercise. The additive factors method enables one to stipulate that if fatigue interacts with subjects' reaction time in a decision task, central processing is affected by fatigue. While pedaling at different intensities, 13 physically-fit men had to perform a series of short-term memory tests. The tests were executed during a constant workload session and a progressive workload session in which subjects pedaled until exhaustion. Subjects provided ratings on Borg's 1970 scale to measure the psychological effects of the physical effort such as perceived exertion. Allocation of processing resources was also measured to determine attentional constraints exerted by the dual-task situation. Analysis showed that decision reaction time was affected only during the exhausting bout of the progressive workload session and for the more difficult decision task. We discuss our results in the context of arousal and the allocation of processing resources.
The views of French physicians and nurses of the organization of palliative care have not been previously analyzed. We surveyed opinion on the care of the terminally ill in a 1,000-bed Paris university hospital. Data were obtained in 1992 by non-directed interviews of leading physicians and semi-directed interviews of nurses. Most physicians wished to managed terminal care in their departments. Patients and family preferences were considered in choosing the place for care. Treatment of hospitalized patients should be limited to relieving symptoms. Department heads and senior nurses agreed on most problems encountered in the management of care. The psychological burden borne by nurses was emphasized. Terminal care training and the possibility of consulting experts in palliative care were the main suggestions for improvement cited by both department heads and senior nurses. Integrating this knowledge into the planning process should result in improved care and in increased satisfaction for the care providers.
OBJECTIVES: Isokinetic tests used to assess both muscle function and joint disorders stimulate the entire organism and in particular the cardiovascular system. We evaluated the risk of cardiovascular or vascular impairment during isokinetic knee extension and flexion tests. METHODS: Cardiac electrical activity, heart rate and systolic and diastolic blood pressures were measured in 251 patients during 50-sec isokinetic tests. RESULTS: Abnormal findings were recorded in 15 patients (5.9%) including 6 with altered blood pressure, 4 with altered cardiac electrical activity and 5 with heart rate abnormalities. Maximal heart rate for a given subject recorded during the isokinetic test was 199 beats per minute and heart rate exceeded 190 bpm in 92 subjects (36.6%). Maximal efforts with cardiac barometric charge produced dramatic, occasionally pathological, changes in heart rate or blood pressure. CONCLUSION: These findings emphasize the need to carefully assess patients before isokinetic tests and carefully monitor cardiovascular parameters. A preliminary physical examination and medical surveillance during testing are required.