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Performance and mood-state parameters during 30-day 6 degrees head-down bed rest with exercise training.

The study was designed to determine if performance and mood impairments occur in bed-rested subjects, and if different exercise-training regimens modify or prevent them. Eighteen normal, healthy men were divided on the basis of age, peak oxygen uptake, and maximal isometric knee extension strength into three similar groups: no exercise (NOE), isotonic exercise (ITE), and isokinetic exercise (IKE). A 15-min battery of 10 performance tests and 8 mood and 2 sleep scales were administered daily during ambulatory control, 30 d of absolute bed rest (BR), and 4 d of ambulatory recovery. Performance test proficiency increased (p < 0.05) for all three groups during BR in 7 of 10 tests and there were no consistent significant differences between the three groups. However, during BR, the ITE group was distinguished from the other groups by a decline (p < 0.05) in the activation mood dimension and in two of its constituent scales (motivation and concentration), and by improvement (p < 0.05) in the trouble-falling-asleep and psychological-tension scales. Since few deleterious changes in performance and mood occurred in the three groups and did not exceed baseline ambulatory levels, we conclude that mood and performance did not deteriorate in response to prolonged BR and were not altered by exercise training. However, the decline in activation mood scales in the ITE group may reflect overtraining or excess total workload in this group.

Adult↗

Impaired response to ET(B) receptor stimulation in heart failure: functional evidence of endocardial endothelial dysfunction?

Inotropic effects of selective ET(B) receptor stimulation depend on the functional integrity of the endocardial endothelium (EE), which is negative when it is intact and positive when it is damaged. These results have been attributed to the existence of two subtypes of ET(B) receptors in the heart: (i) ET(B1), located on the EE, decreases inotropy; (ii) ET(B2), located on myocardial cells, increases inotropy. In the present study we investigated the functional integrity of the EE in a heart failure (HF) model (doxorubicin-induced cardiomyopathy) by evaluating the contractile response to ET(B1) receptor stimulation. New Zealand White rabbits were treated with doxorubicin (DOX-HF, 1 mg/kg, iv, twice weekly for 8 weeks) or with saline. Contractile effects of increasing doses of a selective agonist of endothelial ET(B) receptors, IRL-1620 (10(-9) to 10(-6) M), were studied in papillary muscles (Krebs-Ringer: 1.8 mM CaCl2, 35 degrees C) from control (n = 10) and DOX-HF rabbits (n = 7). Isotonic and isometric twitches were recorded and analyzed. Reported parameters included active tension (AT) and maximum velocities of tension rise (dT/dt(max)) and decline (dT/dt(min)). On echocardiography, DOX-HF rabbits had increased left ventricular (LV) end-diastolic and end-systolic diameters and reduced ejection fraction (52% +/- 2% vs. 61% +/- 1%). Contrary to control papillary muscles, DOX-HF muscles showed a steady decrease in contractility between 1 and 4 Hz. In the control group, IRL-1620 induced dose-dependent negative inotropic and lusitropic effects that decreased at 10(-6) M: 26% +/- 3%, AT; 17% +/- 3%, dT/dt(max); and 16% +/- 5%, dT/dt(min). In the DOX-HF group, these effects were significantly reduced. At the same concentration, IRL-1620 decreased AT (8% +/- 3%) and dT/dt(max) (8% +/- 3%), without significantly affecting dT/dt(min). This study showed an impaired response to endothelial ET(B) receptor stimulation, providing for the first time strong evidence of the occurrence of EE dysfunction in the failing heart and further highlighting the potential use of ET(B) receptor stimulation as a marker of EE function.

Animals↗

Mechanical properties of the electrically silent adult rat soleus muscle.

The isometric and isotonic in situ mechanical properties of the soleus muscle of adult female rats were determined after 60 days of inactivity induced by spinal cord isolation (SI). Compared to control, the absolute muscle mass, physiological cross-sectional area, and maximum tetanic tension of the soleus in SI rats were reduced by 69%, 66%, and 77%, respectively. Isometric twitch time-to-peak-tension and half-relaxation times were 41% and 60% shorter in SI than control rats. The maximum velocity of shortening (mm/s), as determined using the afterloaded technique, was 66% faster in SI than control rats, whereas unloaded shortening velocity was similar in the two groups (9% faster in SI rats). Peak power was 48% lower in SI than control rats. The SI soleus was 39% more fatigable than control. Thus, the soleus became a smaller, faster, and more fatigable muscle following 60 days of inactivity. In general, the results indicate that the adaptations are of a lesser magnitude than those reported previously following denervation for the same duration. These data provide a baseline for future efforts to experimentally define the mechanisms of neurally mediated, but activity-independent, regulation of the mechanical properties of the rat soleus muscle.

Animals↗

"Cardioplegia on the contractile apparatus level": evaluation of a new concept for myocardial preservation in perfused pig hearts.

UNLABELLED: The concept of a reversible desensitization of the myocardial contractile apparatus for calcium by 2,3 Butanedione Monoxime (BDM) as a method to improve the myocardium's tolerance to cold ischemia was evaluated in normal pig hearts (n = 14). The results were compared to those obtained after application of Bretschneider's HTK cardioplegic solution. METHODS: Series I) After BDM treatment (concentrations: 0-30 mmol/L) the isometric force output and the intracellular calcium transients (measured using the FURA-2 ratio method) of electrically driven (1 Hz) isolated left-ventricular muscle strips excised from beating pig hearts (n = 14) were recorded simultaneously in order to analyse the mode of action of BDM; Series II) The cardioprotective effects of BDM (30 mmol/L) and Bretschneider's cardioplegic solution (HTK) were compared in a large-animal model: after "in situ perfusion" of pig hearts with either 2000 ml ice-cold BDM solution (30 mmol/L) (n = 7) or 2000 ml HTK (n = 7) the hearts were explanted and stored at 4 degrees C in the same solutions for up to 42 h. The contractile properties of muscle fibres, excised after storage periods of 8, 24, and 42 h from these hearts were analyzed in terms of isometric force development and isotonic shortening. 280 muscle fibres from 14 pigs were used for measurements. RESULTS: Series I) In pig myocardium a dose-dependent reduction of isometric force development was found after BDM application. The shape and the amplitude of the intracellular calcium transient were also affected by BDM. At 30 mmol/L BDM no force development could be elicited despite the presence of an intracellular calcium transient (amplitude < 70% of the control). Series II) Shortening, calcium transient, and force of left-ventricular muscle strips of pig myocardium excised after storage periods for up to 42 h showed complete recovery when BDM was applied. In contrast HTK perfusion allowed complete recovery of these parameters when the storage period did not exceed 6 hours. CONCLUSION: Under the given experimental conditions reversible desensitization of the contractile apparatus for calcium results in a considerable prolongation of the tolerance to cold ischemia in explanted pig hearts. The present study shows that the protective effects of BDM are not only present when isolate muscle fibres were stored (and the extracellular space is large) but also after storage of complete hearts in a solution in a solution containing BDM. Thus BDM may become a useful agent to enlarge the storage period of donor hearts in heart transplatation considerably.

Animals↗

Reduced isotonic sarcomere shortening in rabbit right ventricular pressure overload hypertrophy.

We found previously that sarcomere shortening was reduced in hypertrophied rabbit right ventricular (RV) trabeculae, even when total isometric force and damaged end compliance were the same as normal. Here we studied isotonic shortening of similar preparations force-clamped with a servomotor. A force clamp holds the length of damaged end compliance constant. Sarcomere length (SL) was measured with laser diffraction in twitches with single and optimally paired stimuli. delta SL was sarcomere shortening divided by SL at the onset of shortening. Muscle shortening divided by unloaded muscle length (ML) at the onset of shortening was delta ML. RV hypertrophy was produced with pulmonary artery constriction in 11 rabbits and there were eight normal rabbits. delta SL was smaller than normal in hypertrophy, but delta ML was unchanged from normal. delta SL/delta ML in hypertrophy, 0.90 +/- 0.02, was significantly less than normal, 2.40 +/- 0.07 (mean +/- S.E.M.) (P less than 0.01). delta SL/delta ML did not depend on sarcomere shortening, load, time during shortening or stimulus pattern. Therefore, the reduced delta SL in hypertrophy was independent of contractile state parameters. The ratio was also independent of resting SL (normal = 2.29 +/- 0.07 microns; hypertrophy = 2.23 +/- 0.03 microns; P greater than 0.05) or where diffraction was sampled along central muscle length. One explanation for the findings includes reduced compliance of series viscoelastic elements within the central undamaged region of a hypertrophied muscle. This explanation is consistent with changes from normal in myocardial mechanics and connective tissue in cardiac hypertrophy. Ventricular function remains adequate in hypertrophy without heart failure perhaps because reduced delta SL/delta ML in hypertrophy results in less sarcomere work at any level of muscle work.

Animals↗

Mechanical properties of skinned rabbit psoas and soleus muscle fibres during lengthening: effects of phosphate and Ca2+.

1. Mechanical properties of permeabilized single fibres from rabbit psoas and soleus muscle were determined by measuring the length responses due to abrupt changes in load and the force responses due to isovelocity length changes at different phosphate and Ca2+ concentrations. 2. The length responses due to abrupt increases in load from psoas fibres showed a rapid lengthening during the change in load followed by a phase of lengthening during which the velocity gradually decreased. In soleus fibres an abrupt lengthening during the change in load was followed by a phase of lengthening during which the velocity remained constant or decreased slightly for increases in load to less than 1.45 of the isometric force (F0). For larger increases in load the velocity during this later phase first increased and thereafter decreased. 3. The initial force-velocity curve, derived from the early part of the isotonic responses after the change in load, as well as the late force-velocity curve derived from the force level attained during isovelocity length changes, were sensitive to phosphate. Phosphate caused a shift of the absolute force-velocity curves of both psoas and soleus fibres towards lower values of force. In psoas fibres, the relative force-velocity curves derived by normalization of the force level to the force developed isometrically was shifted by phosphate to smaller velocities. In soleus fibres, the initial velocity at low and intermediate relative loads (less than 1.75 F0) was increased by phosphate but at higher loads it decreased, while the late force-velocity curve showed an overall decrease in velocity. 4. The force responses during isovelocity lengthening of psoas fibres showed an early rapid increase in force followed by a slow rise in force. The position of this break point in force was sensitive to the phosphate concentration. In soleus fibres, the force responses without phosphate showed an overshoot followed by a slow rise in force. The overshoot diminished with increasing phosphate concentration. 5. Phosphate and Ca2+ affected the force responses in psoas and soleus fibres in different ways. When the isometric starting levels were the same, force during and after the length change at submaximal activation was always less than at maximal activation in the presence of 15 mM-phosphate. 6. The changes in the mechanical performance during lengthening caused by phosphate in psoas as well as in soleus fibres, are in agreement with a decrease in the average force per attached crossbridge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Single muscle fibre contractile properties in young and old men and women.

The purpose of this study was to determine whether there was an age-related decline in the isometric and isotonic contractile function of permeabilized slow (MHC I) and fast (MHC IIa) single muscle fibres. Vastus lateralis muscle fibres from six young men (YM; 25 +/- 1 years), six young women (YW; 25 +/- 1 years), six old men (OM; 80 +/- 4 years) and six old women (OW; 78 +/- 2 years) were studied at 15 degrees C for in vitro force-velocity properties, peak force and contractile velocity. Peak power was 23-28 % lower (P < 0.05) in MHC I fibres of YW compared to the other three groups. MHC IIa peak power was 25-40 % lower (P < 0.05) in OW compared to the other three groups. No difference was found in MHC I and IIa normalized peak power among any of the groups. Peak force was lower (P < 0.05) in the YW (MHC I fibres) and OW (MHC IIa fibres) compared to the other groups. Differences in peak force with ageing were negated when normalized to cell size. No age-related differences were observed in single fibre contractile velocity of MHC I and IIa fibres. These data show that YW (MHC I) and OW (MHC IIa) have lower single fibre absolute peak power and peak force compared to men; however, these differences are negated when normalized to cell size. General muscle protein concentrations (i.e. total, sarcoplasmic and myofibrillar) from the same biopsies were lower (4-9 %, P < 0.05) in the OM and OW. However, myosin and actin concentrations were not different (P > 0.05) among the four groups. These data suggest that differences in whole muscle strength and function that are often observed with ageing appear to be regulated by quantitative rather than qualitative parameters of single muscle fibre contractile function.

Actins↗

Hydration effects on muscle response.

The effect of bathing toad sartorius muscle in hypotonic solutions is studied. The twitch, tetanus force and active stiffness increase as the tonicity decreases from 1.0 R to 0.6 R and then decrease below 0.6 R. Explanation is given in terms of the effect on ATP-ase activity.

Animals↗

Tonic tone in arteries exposed continuously to angiotensin II in vitro.

We evaluated long-term actions of angiotensin II (ATII) on arterial smooth muscle. In isolated sympathectomized renal artery segments that had been denuded of endothelium, isometric force was recorded during 3 days of incubation in nutrient medium with and without 1 microM ATII. The peptide induced, after an acute transient contraction and a latency of at least 12 hr, a slowly developing tonic increase in wall tension. This chronic effect was not influenced by indomethacin but could be reversed by sodium-nitroprusside. In vessels that had been chronically exposed to ATII, acute contractile responses to high potassium, serotonin and ATII were not altered. Also effects on agonist-induced tone of removal and readministration of extracellular potassium were not modified. Relaxing responses after exposure to NH4Cl were attenuated. During continuous exposure of isolated arteries to ATII, release of a stable contractile factor could not be detected, nuclear incorporation of the thymidine analog 5-bromo-2'-deoxyuridine was not stimulated, but the media cross-sectional area was significantly increased. These observations indicate that ATII induces in arterial smooth muscle, besides its well known acute contractile effect and its trophic action, a long-term tonic increase in tone. The mechanism largely remains to be established, but may involve altered cellular handling of hydrogen ions.

Angiotensin II↗

A premovement silent period does not occur prior to rapid changes of velocity during human limb movements.

Surface electromyographic activity (EMG) of the interosseous dorsalis I, the hand extensors and the biceps muscles was analysed in human young normal subjects for the occurrence of a precontraction (PCSP) or a premovement silent period (PMSP) before a sudden increase in tension or rapid change of position after a small isometric contraction or slow isotonic movement. Contrary to the results of Conrad et al. (Exp. Brain Res., 51 (1983) 310-313), in whose experiments the contraction condition changed from isometric to isotonic, a PCSP or PMSP could never be observed in our experiments, where contractions or movements first started at a low force level or with a low speed which had to be changed most rapidly after 2 s and where the recording condition remained strictly either isometric or isotonic. It is concluded that the central nervous system resets the motoneuronal pool activity when the central program is changed from the control of an isometric to the control of an isotonic contraction.

Adult↗

Experimental hyperthyroidism IV. Myocardial muscle mechanics and oxygen consumption in euand hyperthyroidism.

Myocardial mechanics and oxygen consumption were studied in right ventricular papillary muscles taken from cats pretreated with cristalline L-thyroxine (1 mg/kg/day, i.p.) 8-18 days prior to the examination. Isotonic afterloaded and isometric contractions were employed. Oxygen consumption was determined polarographically. Data obtained were compared with control studies on papillary muscles taken from euthyroid cats. In isotonic afterloaded contractions the extent of shortening was nearly identical in both groups. However, maximum rate of isometric tension development and velocity of isotonic shortening were considerably increased in hyperthyroid myocardium. Myocardial oxygen consumption was significantly increased in hyperthyroidism, primarily due to an increased maximum rate of isometric tension development and-to a lesser extent-to increased isotonic contraction velocity. In isometric contractions maximum tension development (preload near Lmax) was similar in both groups. However, maximum rate of isometric tension development was markedly increased in hyperthyroidism. A close and linear relationship was found between maximum rate of isometric tension development (isometric contraction) and myocardial oxygen consumption. The results demonstrate increases of velocity factors of myocardial performance in experimental hyperthyroidism. Myocardial oxygen consumption is significantly increased. This increase in oxygen consumption quantitatively has its mechanical equivalent in increased isometric contraction velocity and, to a small amount, in increased isotonic contraction velocity.

Animals↗

Differences in stretch reflex responses of elbow flexor muscles during shortening, lengthening and isometric contractions.

Stretch reflexes were evoked in elbow flexor muscles undergoing three different muscle contractions, i.e. isotonic shortening (SHO) and lengthening (LEN), and isometric (ISO) contractions. The intermuscle relationships for the magnitude of the stretch reflex component in the eletromyographic (EMG) activities of two main elbow flexor muscles, i.e. the biceps brachii (BB) and the brachioradialis (BRD), were compared among the three types of contractions. The subjects were requested to move their forearms sinusoidally (0.1 Hz) against a constant pre-load between elbow joint angles of 10 degrees (0 degrees = full extension) and 80 degrees during SHO and LEN, and to keep an angle of 45 degrees during the ISO. The perturbations were applied at the elbow angle of 45 degrees in pseudo-random order. The EMG signals were rectified and averaged over a period of 100 ms before and 400 ms after the onset of the perturbation 40-50 times. From the ensemble averaged EMG waveform, the background activity (BGA), short (20-50 ms) and long latency (M2, 50-80, M3, 80-100 ms) reflex and voluntary activity (100-150 ms) components were measured. The results showed that both BGA and reflex EMG activity of the two elbow flexor muscles were markedly decreased during the lengthening contraction compared to the SHO and ISO contractions. Furthermore, the changes of reflex EMG components in the BRD muscle were more pronounced than those in the BB muscle, i.e. the ratios of M2 and M3 magnitudes between BRD and BB (BRD:BB) were significantly reduced during the LEN contractions. These results would suggest that the gain of long latency stretch reflex EMG activities in synergistic muscles might be modulated independently according to the model of muscle contraction.

Adult↗