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Cyclic analogues of bradykinin. IV. Structure-function relationships in the series of bradykinin cycloanalogues.

A study of the biological activity of six bradykinin and kallidin cycloanalogues has revealed that all of them exhibit prolonged hypotensive activity except the inactive cyclo-(omega-aminododecanoyl-omega-aminododecanoyl-bradykini n) (CADADB) when assayed in anaesthetized rats in vivo. The threshold dose of cyclo-bradykinin (CB) in these experiments was found to be 250 micrograms/kg of body weight. A single dose (500 micrograms/kg) of this cyclopeptide produces a decrease in the arterial pressure of rats up to 40 mm Hg for more than 2 h. The hypotensive action of other cyclopeptides under the same conditions is characterized by the following values: cyclo-[epsilon-(L-Lys1, Gly6)-bradykinin] (CLGB), alpha-L-Arg-cyclo-[epsilon-(L-Lys1, Gly6)-bradykinin] (ACLGB) and cyclo-epsilon-kallidin (CK) - 5 micrograms/kg, 40 mm Hg, over 2 h; cyclo-(omega-aminododecanoyl-bradykinin) (CADB) - 50 micrograms/kg, 250 micrograms/kg, 40 mm Hg, 35 min. Some cyclopeptides appeared to possess myotropic activity in vitro on isolated rat uterus preparations: CB (alpha = 0.52, pD2 = 7.86), CK (alpha = 1.0, pD2 = 7.56), CADB (alpha = 0.81, pD2 = 6.41). CLGB, ACLGB and CADADB failed to show myotropic activity. In contrast to CLGB and CADB, CK was hypotensive in dogs. CB acts as a weak antagonist of bradykinin (pA2 = 5.09 +/- 0.06) on rat uterus in vitro. It is believed that the hypotensive action within this series of compounds is primarily determined by the cycle size, whilst their myotropic activity is due to the presence of a "common" fragment Arg-Pro-Pro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comments on "growth of a hypercycle" by King (1981).

The notion of hypercycles has been introduced (Eigen, 1971) in order to characterize a functional entity which integrates information stored in individual self-replicating elements. Commonly, these self-replicating elements compete, like polynucleotides do in test tube experiments (Spiegelman, 1971; Biebricher et al., 1981) or, like species do in nature. A single species is selected eventually together with its most frequent mutants and the less efficient competitors disappear. In order to suppress competition, specific coupling terms of second order - these are coupling terms which are proportional to the product of two population numbers or concentration - have to be introduced into the kinetic equations such a link has to extend to all members, requiring the formation of a closed catalytic cycle (Eigen and Schuster, 1979). The copying of polynucleotide sequences, like every transfer of information, can only occur with finite accuracy (Eigen et al., 1981). This physical restriction imposes a limit upon the content of information that can be transmitted. A higher content of information requires more precise replication. A more involved replication machinery, however, presupposes more information to build it. Thus, a single autocatalyst will not be able to increase its content of information over the given threshold. How does one escape from this vicious circle? Hypercycles present a solution to the problem: many information carriers coexist and may cooperate to build a more sophisticated and more precisely copying replication machinery. Optimization of growth rates has never been the goal for which hypercycles were conceived. Any first order process can proceed at a higher rate than a second order process if low enough concentrations are chosen. On the other hand, any realistic hypercycle involves both first and second order terms. At low concentrations first order terms provide for accumulation of material while at higher concentration second order terms stabilize cooperation. At which concentration level such a prevalence changes is a matter of quantitative values of rate parameters rather than of basic principle. An autocatalyst may outgrow a hypercycle under certain conditions but it can never solve the problem of integrating information.

Models, Chemical↗

Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic.

The sperm chromatin structure assay (SCSA) was used to measure over 500 human semen samples from two independent studies: Study I, 402 samples from 165 presumably fertile couples wishing to achieve pregnancy over 12 menstrual cycles; Study II, samples from 115 patients seeking fertility counselling. The SCSA measures susceptibility to DNA denaturation in situ in spermatozoa exposed to acid for 30 s, followed by acridine orange staining. SCSA data from the male partners of 73 couples (group 1) achieving pregnancy during months 1-3 of Study I were used as the standard of 'sperm chromatin compatible with high fertility' and were significantly different from those of 40 couples (group 3) achieving pregnancy in months 4-12 (P < 0.01) and those of male partners of 31 couples (group 4) not achieving pregnancy (P < 0.001). Group 2 contained couples who had a miscarriage. SCSA values for Study II were almost twice that of the Study I fertility standards. Within-couple repeatability tended to be less for group 3 than for groups 1, 2 or 4. Based on logistic regression, spermatozoa with denatured DNA (cells outside the main population, COMP alpha t) were the best predictor for whether a couple would not achieve pregnancy. Some 84% of males in group 1 had COMP alpha t < 15%, while no couples achieved pregnancy in group 1 with > or = 30% COMP alpha t, a threshold level considered not compatible with good fertility. Using selected cut-off values for chromatin integrity, the SCSA data predicted seven of 18 miscarriages (39%).

Chromatin↗

Mathematical models of cochlear nucleus onset neurons: II. model with dynamic spike-blocking state.

Onset (On) neurons in the cochlear nucleus (CN), characterized by their prominent response to the onset followed by little or no response to the steady-state of sustained stimuli, have a remarkable ability to entrain (firing 1 spike per cycle of a periodic stimulus) to low-frequency tones up to 1000 Hz. In this article, we present a point-neuron model with independent, excitatory auditory-nerve (AN) inputs that accounts for the ability of On neurons to both produce onset responses for high-frequency tone bursts and entrain to a wide range of low-frequency tones. With a fixed-duration spike-blocking state after a spike (an absolute refractory period), the model produces entrainment to a broad range of low-frequency tones and an On response with short interspike intervals (chopping) for high-frequency tone bursts. To produce On response patterns with no chopping, we introduce a novel, more complex, active membrane model in which the spike-blocking state is maintained until the instantaneous membrane voltage falls below a transition voltage. During the sustained depolarization for a high-frequency tone burst, the new model does not chop because it enters a spike-blocking state after the first spike and fails to leave this state until the membrane voltage returns toward rest at the end of the stimulus. The model entrains to low-frequency tones because the membrane voltage falls below the transition voltage on every cycle when the AN inputs are phase-locked. With the complex membrane model, On response patterns having moderate steady-state activity for high-frequency tone bursts (On-L) are distinguished from those having no steady-state activity (On-I) by requiring fewer AN inputs. Voltage-gated ion channels found in On-responding neurons of the CN may underlie the hypothesized dynamic spike-blocking state. These results provide a mechanistic rationale for distinguishing between the different physiological classes of CN On neurons.

Acoustic Stimulation↗

Regulation of follicle development and novel approaches to ovarian stimulation for IVF.

Current ovarian stimulation regimens for IVF are complex and not without risk. Increasing our knowledge of the physiology of follicle development and dominant follicle selection may enable the design of less complex, safer and cheaper ovarian stimulation regimens for IVF. Decremental serum FSH concentrations during the follicular phase of the menstrual cycle are required for single dominant follicle selection. Only the most mature follicle will continue its development due to increased sensitivity for stimulation by FSH. FSH stimulation becomes insufficient for less mature follicles and remaining cohort follicles will therefore go into atresia. The number of days during which FSH is above the threshold for stimulation of follicle development is limited, resulting in a narrow FSH window. More medium sized and large pre-ovulatory follicles and increased oestradiol output can be induced by the administration of small doses of exogenous FSH during the mid- to late follicular phase, preventing the physiological decrease in FSH stimulation. Intervention with decremental serum FSH concentrations in combination with gonadotrophin-releasing hormone (GnRH) antagonists to prevent a premature rise in serum LH may induce ongoing growth of multiple follicles sufficient for IVF. The benefits and risks of these minimal hyperstimulation protocols require further evaluation.

Female↗

Electrophysiological effects of alpha 2-adrenergic stimulation in canine cardiac Purkinje fibers.

The effects of alpha 2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 microM l-norepinephrine + 0.5 microM dl-propranolol (NE+P) from baseline values of 166 +/- 7 and 249 +/- 9 (SE) ms (n = 7) to 174 +/- 7 and 265 +/- 9 ms, respectively (P < 0.05 for both). Selective alpha 2-blockade with 0.01 microM yohimbine (YO) reduced this prolongation by NE+P in APD50 and APD90 to 169 +/- 7 and 256 +/- 8 ms, respectively (P < 0.05 compared with NE+P). Additional selective alpha 1-blockade with 0.01 microM prazosin (PZ) completely blocked the effects of NE+P, returning APD50 and APD90 to 163 +/- 7 and 250 +/- 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 microgram/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 +/- 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE+P, but the effects of PZ were intact. The effects of alpha 2-stimulation on beta-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE+PZ (beta- + alpha 2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE+PZ+YO (unopposed beta-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under beta-stimulation, could no longer be elicited in the presence of beta- + alpha 2-stimulation. These results suggest that the postjunctional alpha 2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by beta-adrenergic stimulation.

Action Potentials↗

Exercise performance after lung transplantation.

Heart-lung, double lung, and single lung transplantation have been shown to be effective in the treatment of patients with advanced cardiopulmonary disorders. An overlap in indications occurs for the different procedures, and in many situations the factors that are important in selecting the best operation for a given patient have not been clearly elucidated. To determine whether the anticipated exercise capacity should be an important consideration in the selection of the optimal procedure for a given patient, we compared exercise performance in patients who had undergone the different lung transplantation procedures in the preceding year and were otherwise well. Eleven heart-lung, six double lung, and 16 single lung recipients and 28 control subjects underwent maximal symptom-limited incremental exercise tests using a cycle ergometer. At peak exercise, transplant recipients reached maximum oxygen uptakes in the range of 40% to 60% of predicted values; no significant differences existed between the means of the different transplant groups. Ventilatory factors did not appear to limit exercise in any group. The exercise responses in the transplant subjects were characterized by reduced aerobic capacity and diminished oxygen pulse, factors indicating abnormal cardiovascular performance. Our data indicate that moderate levels of exercise can be anticipated early after heart-lung, double lung, and single lung transplantation. In the absence of substantial differences in exercise capacity, other considerations would appear to be more important in guiding the selection of the optimal lung replacement procedure for an individual patient.

Adult↗

[Frequency specificity of ABR evaluated by tuning curves].

A tone on tone simultaneous masking paradigm was used to determine tuning curves of ABR both from the normal and hearing-impaired subjects. ABR tuning curves were constructed to define masker intensity that resulted in a 50% reduction in probe elicited wave V amplitude. The frequency specificity of each probe stimulus was evaluated by Q10, low cut-off slope, high cut-off slope and the maximum masker frequency calculated for the tuning curves. The results were as follows; 1) Q10, low cut-off slope and high cut-off slope increased gradually with the increase in rise time. However, prolongations of the rise time beyond 3 cycles of probe frequency yielded little improvement in Q10, low cut-off slope and high cut-off slope. 2) Q10, low cut-off slope and high cut-off slope for normal-hearing subjects increased gradually with the increase in stimulus frequency or the decrease in stimulus pressure. Maximum masker frequency of the tuning curves was not always equal to the frequency of probe without the 2-kHz. For the 0.5, 1kHz probe, the maximum masker frequency of the tuning curves showed higher values than the frequency of probe. For the 4kHz probe, the maximum masker frequency of the tuning curves showed lower values than the frequency of probe. The results indicate that the tone pip stimuli will allow to assess certain conditions of auditory function at different frequencies, and they show wider frequencies' spread in the cochlea area near stimulus frequencies. 3) For subject with abrupt high-frequency hearing loss (30dB/oct), a pronounced down-ward shift of maximum masker frequency, down-ward shift of high cut-off slope and up-ward shift of low cut-off slope were found when the probe was placed in the region of elevated threshold. For subject with low-frequency hearing loss (25dB/oct), a pronounced up-ward shift of maximum masker frequency, down-ward shift of low cut-off slope were found. Maximum masker frequency, low and high cut-off slope of hearing-impaired subjects were not always equal to those of normal subjects for same probe. Especially the value of the maximum masker frequency shifted to the direction in which the most sensitive frequency was observed in audiogram. The threshold of ABR reflected the cochlea function of the most sensitive area near stimulus frequencies. Greatest predictive error was observed in steeply sloping audiograms.

Adult↗

Respiratory drive and breathing pattern during exercise in man.

Changes in respiratory drive, as assessed by mouth occlusion pressure (P0.1), and in breathing pattern were studied in 19 healthy subjects who exercised on a cycle ergometer with work loads ranging from loadless pedalling up to the highest load that could be sustained for 4 min. In the P0.1 studies, experiments were carried out both at normal atmospheric pressure and during hyperbaric conditions in which the density (D) of the respired gas was increased. Analyses of observed changes in P0.1 and in the interrelations of minute ventilation (V), tidal volume (VT), inspiratory (TI), expiratory (TE) and total breath (Ttot) durations, and lung volumes yielded the following results and conclusions: Analyses of inspiratory and expiratory volume threshold curves in terms of the relations between end-inspiratory volume and TI on one hand, and end-expiratory volume and TE on the other, suggest that the termination of inspiration during cycle exercise is dependent on volume-related afferent feedback from the lungs and/or chest wall, not only in the high but also in the low volume range, and expiratory muscle activity occurs already at low exercise intensities, combined with active control of expiratory flow, end-expiratory volume and TE as exercise hyperpnea intensifies. TI/Ttot increased with V and work intensity through a number of mechanisms which accelerate the increase in mean expiratory flow compared with that in mean inspiratory flow (VT/TI), the change in timing presumably reducing the oxygen cost of respiration at any given exercise-induced ventilatory demand. With increments in work load, P0.1 increased at higher rates than V and VT/TI, both in the normo- and hyperbaric conditions. Respiratory impedance, P0.1/(VT/TI), increased with both D and VT/TI. The relationship of P0.1, D and VT/TI approximated the equation P0.1 = K X D0.5(VT/TI)b, where K varies among subjects due to differences in i.a. vital capacity, and b has a value close to 1.5. The observed changes in P0.1 suggest that the respiratory drive was reflexly enhanced in response to loading as airway resistance increased with D and/or VT/TI, whereby any depression of V or VT/TI attributable to the increased respiratory impedance was counteracted.

Adult↗

Effects of acute aerobic and anaerobic exercise on blood markers of oxidative stress.

The purpose of this study was to compare oxidative modification of blood proteins, lipids, DNA, and glutathione in the 24 hours following aerobic and anaerobic exercise using similar muscle groups. Ten cross-trained men (24.3 +/- 3.8 years, [mean +/- SEM]) performed in random order 30 minutes of continuous cycling at 70% of Vo(2)max and intermittent dumbbell squatting at 70% of 1 repetition maximum (1RM), separated by 1-2 weeks, in a crossover design. Blood samples taken before, and immediately, 1, 6, and 24 hours postexercise were analyzed for plasma protein carbonyls (PC), plasma malondialdehyde (MDA), and whole-blood total (TGSH), oxidized (GSSG), and reduced (GSH) glutathione. Blood samples taken before and 24 hours postexercise were analyzed for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). PC values were greater at 6 and 24 hours postexercise compared with pre-exercise for squatting, with greater PC values at 24 hours postexercise for squatting compared with cycling (0.634 +/- 0.053 vs. 0.359 +/- 0.018 nM.mg protein(-1)). There was no significant interaction or main effects for MDA or 8-OHdG. GSSG experienced a short-lived increase and GSH a transient decrease immediately following both exercise modes. These data suggest that 30 minutes of aerobic and anaerobic exercise performed by young, cross-trained men (a) can increase certain biomarkers of oxidative stress in blood, (b) differentially affect oxidative stress biomarkers, and (c) result in a different magnitude of oxidation based on the macromolecule studied. Practical applications: While protein and glutathione oxidation was increased following acute exercise as performed in this study, future research may investigate methods of reducing macromolecule oxidation, possibly through the use of antioxidant therapy.

8-Hydroxy-2'-Deoxyguanosine↗

Centralis superior raphe, reticularis pontis nuclei, and sleep-wakefulness cycle in cats.

This study examines the influence of lesions in the centralis superior raphe nucleus (CeSR) and adjacent paramedial pontine tegmentum on the sleep/wakefulness cycle (SWC) in cats. Sixteen cats had electrodes implanted for electro-oculogram (EOG), electromyogram (EMG), electroencephalogram (EEG) and ponto-geniculo-occipital (PGO) recordings. There were 10 experimental animals: seven animals received diathermocoagulation lesions destroying between 7 and 27% of the CeSR; the remaining three cats suffered bilateral lesions in the paramedial portion of the reticularis pontis oralis (RPO) and caudalis (RPC) nuclei. Six sham-operated animals were used as controls. Recordings were taken of all animals in continuous 23-h sessions once a week for 12 weeks. Results indicated that the threshold for SWC state changes (increase of wakefulness (W) and drowsiness (D), and decrease of slow wave sleep (SWS)) after CeSR lesion is approximately 11.3% following volumetric destruction of the nucleus. The amount of CeSR damage (CeSR-D) only correlated significantly with the amount of W (positive correlation) and SWS (negative correlation) during the first week post-lesion. The changes in W over the course of the study were different in the two experimental groups. In both groups, total W was increased with respect to the controls, however, these increases were observed earlier in the CeSR-D group. The return to near control values in SWC state over days 15-28 of the study does not represent a definitive recovery by the CeSR-D cats. All the SWC states returned to control values by the tenth week in the cats with paramedial reticular pontine damage.

Animals↗

Optimal frequencies for electric stimulation using medium-frequency alternating current.

OBJECTIVE: To determine the effect of single cycles of alternating current of various frequencies on sensory and motor thresholds and on relative thresholds (motor threshold/sensory threshold). DESIGN: Repeated-measures design. SETTING: Laboratory setting. PARTICIPANTS: University student and staff volunteers (N=16; mean age, 34y). INTERVENTIONS: Single cycles of sinewave frequencies between 1 and 35kHz were delivered at 50Hz. The frequencies were applied in a random order. MAIN OUTCOME MEASURES: The motor and sensory thresholds were recorded at each applied frequency. RESULTS: Both sensory and motor thresholds showed a smooth decrease to a minimum at approximately 3kHz. The relative threshold reached a minimum close to 9kHz. Comparison with previous studies showed that although absolute thresholds reach a minimum at a frequency that depends on electrode size, the frequency at which the relative threshold is a minimum was independent of electrode size and independent of whether the stimulus was applied as single pulses or in burst mode. CONCLUSIONS: The optimal frequency for transcutaneous stimulation using medium-frequency alternating current depends on the outcome measure used. It would therefore be desirable for clinical stimulators to provide a selection of carrier frequencies.

Adult↗

Maximal lactate steady state determination with a single incremental test exercise.

The aim of this study was to determine whether the power output associated with a maximal lactate steady state (MLSS) (.W(MLSS)) can be assessed using a single incremental cycling test. Eleven recreational sportsmen (age: 22+/-1 years, height: 175+/-6 cm, weight: 71+/-5 kg) volunteered to participate in the study. For each subject the first and second ventilatory thresholds (VT(1) and VT(2), respectively) and the power output corresponding to (respiratory exchange ratio) RER=1.00 were determined during an incremental test to exhaustion. Thereafter, each subject performed several 30-min constant load tests to determine MLSS. The workload used in the first constant test was set to the .W(RER=1.00) determined during the incremental test. .W(VT1) (175+/-24 W) and .W(VT2) (265+/-31 W) were significantly different from .W(MLSS )(220+/-36 W). Whereas, .W(RER=1.00) (224+/-33 W) was similar to .W(MLSS). HR, RER and .VE were significantly different between the 10th and the 30th minutes when exercising at .W(RER=1.00) and at .W(MLSS). In contrast, .VO(2) and .VCO(2) were stable over those 30-min constant tests. Power output at VT(1), RER=1.00 and VT(2) were all correlated to .W(MLSS) but the relationship was stronger between RER=1.00 and MLSS (R (2)=0.95). The present study shows that the power output associated with a RER value equal to 1.00 during an incremental test does not differ from that determined for MLSS. Hence, the MLSS can be estimated with a single exercise test.

Adult↗

Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): steady-state pharmacokinetics of MPA and E2 in surgically sterile women.

The steady-state pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate (MPA) and estradiol (E2, released from E2C by esterase enzymes) were characterized after administration to surgically sterile women. This report describes the pharmacokinetics of this multiple-dose and open-labeled study (pharmacodynamics are reported in a subsequent article in this issue). Women with regular menstrual cycles were studied for one control cycle, 3 consecutive treatment months, and 3-5 months of follow-up. Blood samples were drawn before each monthly dose and at specified time points after the third monthly injection. A total of 16 women were enrolled, 14 of whom completed the study. These 14 women (13 white, one black) ranged in age from 28 to 43.4 years, in body weight from 47.6 to 68.9 kg, and in height from 150 to 175 cm. Mean serum MPA concentrations peaked in the first week after administration of MPA/E2C (Lunelle Monthly Contraceptive Injection). The mean MPA Cmax and AUC0-t(last) were 1.25 ng/mL and 32.13 ng.day/mL, respectively. Serum MPA concentrations declined with a mean terminal half-life of 14.7 days, indicating that absorption from the injection site is prolonged after administration of MPA/E2C. The time for MPA concentrations to fall below the lower limit of quantitation (i.e., < 10 pg/mL) after the third injection ranged from 63 to 84 days. The average MPA trough (Cmin' day 28) concentrations for the three consecutive monthly injections ranged from 0.44 to 0.47 pg/mL, indicating that steady-state conditions were achieved after the first injection. The MPA Cmin values were well above threshold levels required to suppress ovulation throughout the injection interval. Absorption of E2 from the injection site was also prolonged after injection of MPA/E2C. Mean concentrations of E2 peaked at approximately 2 days after the third injection, and the average Cmax was 247 pg/mL. Serum E2 levels declined with a terminal half-life of approximately 8 days; E2 levels returned to baseline (typically, approximately 100 pg/mL) by 14 days after each injection. The average trough (Cmin' day 28) levels for E2 ranged from 40 to 55 pg/mL. The results of this study demonstrate that steady-state conditions are achieved after the first injection of MPA/E2C; no further MPA or E2 accumulation occurs beyond the first injection. Furthermore, the E2 peak observed after injection of MPA/E2C is similar to the nontreated preovulatory E2 range and returns to baseline levels by approximately 14 days after injection.

Absorption↗

Effect of the Wingate test on mechanomyography and electromyography.

The purpose of this investigation was to examine mechanomyographic (MMG) and electromyographic (EMG) amplitude responses of the superficial quadriceps femoris muscles during the Wingate Anaerobic Test (WAnT). Ten healthy adults (age 21 +/- 1.2 years) volunteered to perform the WAnT on a calibrated Monark 894E cycle ergometer while the EMG and MMG signals were recorded. The EMG and MMG amplitude and power output (W) values per 5-second segments of the test were averaged and normalized to the highest value found during the test, respectively. The statistical analysis indicated that EMG amplitude did not change significantly over the 30-second test, but W and MMG amplitude decreased significantly. There is dissociation between EMG and MMG amplitude over the 30-second anaerobic test, providing evidence that MMG amplitude could be used as a monitor of W during such a task. MMG amplitude could potentially be used as a direct monitor of mechanical activity, which could be of benefit to those who train athletes when a direct assessment of mechanical contribution from a given muscle to a fatiguing activity is desired (such as when monitoring an injury), but it must be studied under various conditions, such as the current study, before such applications are made.

Adult↗

Interleukin-6 response to exercise and high-altitude exposure: influence of alpha-adrenergic blockade.

Interleukin-6 (IL-6), an important cytokine involved in a number of biological processes, is consistently elevated during periods of stress. The mechanisms responsible for the induction of IL-6 under these conditions remain uncertain. This study examined the effect of alpha-adrenergic blockade on the IL-6 response to acute and chronic high-altitude exposure in women both at rest and during exercise. Sixteen healthy, eumenorrheic women (aged 23.2 +/- 1.4 yr) participated in the study. Subjects received either alpha-adrenergic blockade (prazosin, 3 mg/day) or a placebo in a double-blinded, randomized fashion. Subjects participated in submaximal exercise tests at sea level and on days 1 and 12 at altitude (4,300 m). Resting plasma and 24-h urine samples were collected throughout the duration of the study. At sea level, no differences were found at rest for plasma IL-6 between groups (1.5 +/- 0.2 and 1.2 +/- 0.3 pg/ml for placebo and blocked groups, respectively). On acute ascent to altitude, IL-6 levels increased significantly in both groups compared with sea-level values (57 and 84% for placebo and blocked groups, respectively). After 12 days of acclimatization, IL-6 levels remained elevated for placebo subjects; however, they returned to sea-level values in the blocked group. alpha-Adrenergic blockade significantly lowered the IL-6 response to exercise both at sea level (46%) and at altitude (42%) compared with placebo. A significant correlation (P = 0.004) between resting IL-6 and urinary norepinephrine excretion rates was found over the course of time while at altitude. In conclusion, the results indicate a role for alpha-adrenergic regulation of the IL-6 response to the stress of both short-term moderate-intensity exercise and hypoxia.

Adrenergic alpha-Agonists↗

Recovery of the torque-velocity relationship after short exhausting cycling exercise.

The effects of fatigue upon the torque-velocity (T-omega) relationship in cycling were studied in 11 subjects. Fatigue was induced by short exhausting exercise, on a cycle ergometer, consisting of 4 all-out sprints without recovery. The linear (T-omega) relationship was determined during each all-out sprint, before, during and after the exhausting exercise. The kinetics of the T-omega relationship had permitted the study of the recovery of optimal torque, optimal velocity and their corresponding maximal power outputs (Pmax), 30 s or 1 min after the short exhausting exercise. Fatigue induced a parallel shift to the left of the T-omega relationship which was partly reversed by a parallel shift to the right during recovery. After 30 s recovery optimal velocity, optimal torque and Pmax were slightly lower than the corresponding values before the exhausting exercise; after 1-min optimal velocity and optimal torque had recovered 99% and 97% of their initial values. These mechanical data suggested that the causes of exhaustion were processes that allowed fast recovery of both optimal velocity and optimal torque.

Adult↗

Impaired heart rate response during incremental exercise in patients with acute myocardial infarction and after coronary artery bypass grafting: evaluation of coefficients with Karvonen's formula.

Heart rate (HR) response during exercise in patients with ischemic heart disease was evaluated, and the appropriateness of Karvonen's method for determining rehabilitation exercise target HR was investigated. The study group comprised 24 patients with acute myocardial infarction (AMI) and 37 patients who had undergone coronary artery bypass grafting (CABG). Cardiopulmonary exercise testing (CPX) was performed with a cycle ergometer and changes in HR (deltaHR)/changes in work rate (deltaWR) and interval changes of the coefficient of Karvonen's formula were evaluated. In the AMI group and the CABG group, deltaHR/deltaWR were significantly lower than those of age-matched control subjects (p<0.01). Karvonen's coefficients ranged from 0.37 to 0.54 when calculated from actual peak HR and 0.21 to 0.32 calculated from the predicted peak HR. An impaired HR response was found in patients with AMI and those who had had CABG up to 6 months previously. Because the Karvonen's coefficient values, which ranged from 0.6 to 0.8, were elevated for these patients, and considering the data from the CPX, increased exercise is recommended for such cases.

Adrenergic beta-Antagonists↗