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Both plasma and renal endothelin-1 participate in the acute cardiovascular response to exercise.

Plasma endothelin (ET-1) and renal endothelin are two distinct functional systems involved in maintaining blood volume. To investigate whether plasma and renal ET-1 participate in the cardiovascular response to exercise-induced hypovolaemia, we studied changes in plasma and urinary ET-1 in healthy non-professional athletes after 2 h of jogging performed both without and with drinking isotonic fluids. After the run, which caused a 13% plasma volume (PV) reduction, plasma and renal ET-1 (+117% and +118%) increased significantly (all P < 0.01). Fluid loss restitution during the run significantly attenuated either the PV contraction (-1.2%) and plasma and renal ET-1 increase (+2 and +3%). At multiple regression analysis changes in AVP plasma concentration, and not in PRA or PV per se, were significantly related to ET-1 changes both in plasma and urine. The present findings indicate that both plasma and renal ET-1 participate in the cardiovascular response to hypovolaemia induced by long-lasting, dynamic exercise.

Adult↗

Alterations in mechanical properties of rat papillary muscle during maturation.

Myocardial performance was measured during maturation using isolated left ventricular papillary muscles from female Wistar rats. Muscles were studied isometrically and isotonically, stimulated at 0.1 Hz, perfused with Tyrode solution having an external calcium concentration of 2.4 mM, and maintained at 30 degrees C. Heart and body weight increased rapidly during the first 6 mo and then stabilized. Peak isometric developed tension, time to peak isometric developed tension, and time to half relaxation increased substantially during the 1- to 10-mo period with little change in the peak rate of isometric tension rise and peak rate of isometric tension fall. No difference in resting tension was noted among any groups. Force-velocity curves from muscles from 2-, 6-, and 10-mo-old animals show a significant age-related decrease in the isotonic velocity of shortening by as much as 21% between 2 and 10 mo of age. Thus maturation profoundly affects the contractile state of cardiac muscle, with force of contraction increasing and velocity of shortening decreasing as a function of age in the rat.

Aging↗

[Muscular isokinetic dynamometry].

In the past, muscular strength has primarily been measured using isometric, isotonic or tensiometric techniques. The advent of isokinetic dynamometers has supplied an objective method of measuring peak torque throughout a full range of motion at a predetermined speed of contraction. An isokinetic contraction is a refinement of the controlled motion concept. The isokinetic contraction is dynamic, but the speed of the motion is held constant by a special device. In this way, resistance is in direct ratio to the varying force applied through the full course of a natural movement. The purpose of this study was to determine the peak torque of quadriceps (Q), and hamstrings (H), and their biomechanical angle of production, H to Q ratio and bilateral comparisons of these variables for the first time in a Southamerican population. Twenty healthy and voluntary males (age: 21.9 +/- 3.1 years, height 193.2 +/- 6.5 cm, weight: 84.2 +/- 5.2 kgs.), were tested on the Cybex II Dynamometer and Cybex Data Reduction Computer (CDRC). Quadriceps and hamstrings peak torque (pkTQ), in Newton-meters, were obtained at angular velocities of 60, 180 and 240 degrees. sec-1. Also, the angle of the range of motion at which peak torque occurred in both directions, H and Q peak torque to body weight ratios, H to Q ratio were measured. Finally, CDRC provided the bilateral comparison of the different variables expressed in percentages. All measurements were automatically corrected for the effect of gravity. The absolute maximal pkTQ of dominant (D), and non-dominant (ND), quadriceps at 60 degrees/sec was DQ 297 +/- 25 Nwm and nDQ 303 +/- 13 Nwm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Lusitropic effect and modifications of contraction-relaxation coupling induced by alpha-adrenergic stimulation in rat left ventricular papillary muscle.

Phenylephrine (PE) and metaraminol (MR) were studied alone at 2 x 10(-5) M and at 4 x 10(-5) M respectively. These drugs were also used both in the presence of either propranolol (PR) at 4 x 10(-7) M (PE/PR and MR/PR groups) or prazosin (PZ) at 2 x 10(-7) M (PE/PZ and MR/PZ groups). Specific alpha-adrenergic stimulation (AS) was induced in the PE/PR and MR/PR groups. These AS were evaluated in isotonic and isometric conditions on rat left ventricular papillary muscle. Peak shortening velocity (Vcmax) and peak lengthening velocity (Vrmax) were calculated from the twitch with preload only. Positive (+dF/dtmax) and negative (-dF/dtmax) peak derivative forces were calculated from the isometric twitch. Two coefficients R1 and R2 were used to measure the coupling between contraction and relaxation at low and heavy load, respectively: R1 = Vcmax/Vrmax and R2 = (+dF/dtmax)/(-dF/dtmax). In all groups, there was a significant positive inotropic effect. As compared to control values before AS, R1 significantly decreased in all groups, (PE/PR: -15%; MR/PR: -18%; PE/PZ: -8%; MR/PZ: -23%; PE: -19%; MR: -32%). On the other hand, R2 significantly decreased only in three groups (PE/PZ: -5.4%; MR/PZ: -16.5%; MR: -12.0%) whereas it did not significantly change in the three other groups (PE/PR; MR/PR; PE). In all groups, and at low load, Vrmax increased more than Vcmax (positive relaxant effect i.e. R1 decreased). At heavy load, despite the positive inotropic effect, there was no significant relaxant effect after predominent alpha-AS. These results indicate that alpha-AS modified the coupling between contraction and relaxation differently, depending on the level of load.

Adrenergic alpha-Agonists↗

Relations between muscle soreness and biochemical and functional outcomes of eccentric exercise.

Correlations between functional and biochemical outcomes of eccentric exercise and between these outcomes and "delayed-onset muscle soreness" (DOMS) were studied. Maximal isotonic force, extension and flexion angle of the elbow, creatine kinase activity, and myoglobin concentration in serum were measured in 27 male subjects during 5 days after 120 maximal eccentric contractions of the forearm flexors. Significant correlations were found between values at 1 to 96 h after exercise for force (r = 0.55 to 0.96), flexion (0.52 to 0.94), extension (0.41 to 0.95), and myoglobin (0.55 to 0.97) and at 24 to 96 h for creatine kinase (0.67 to 0.96) and DOMS (0.45 to 0.72). Clusters of significant correlations (0.32 to 0.91) were found among all functional and biochemical measures. DOMS, however, showed only few and lower correlations with the other parameters (0.34 to 0.63). These results can practically be interpreted as follows: 1) subjects need more time to recover completely when early deviations after eccentric exercise are large, 2) a large change in one measure is accompanied by large deviations in other measures, and 3) objective outcomes of eccentric exercise are more accurate parameters than a DOMS score for use in effect studies.

Adult↗

[Experimental studies on the mechanism of action of carbocromen on the isolated cat papillary muscle (author's transl)].

1. In isotonically shortening cat papillary muscle 3-(2-di-ethylaminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen; Intensain¿) (1-30 mug/ml) slightly increases contraction amplitude. 2. At low stimulation rates (6-12/min) the positive inotropic effect is more pronounced. 3. The maximal velocity of depolarization of the monophasic action potential is slightly reduced. 4. At all stimulation frequencies investigated (15-90/min) the total duration of the action potential -- especially at late repolarization level -- is strongly increased. Hence, functional refractory period is prolonged and maximal follow frequency reduced.

Action Potentials↗

Noncalcium-dependent modulation of in vitro atrial natriuretic factor release by extracellular osmolality.

Recent reports have described modulation of atrial natriuretic factor (ANF) secretion by atrial stretch, increased Na+ concentration, and a variety of hormones and neurotransmitters. One problem in the study of ANF secretion has been the isolation of stimulatory effects from interference due to rhythmic myocardial contraction. To avoid this problem, rat atria were dispersed, the myocytes were suspended in a polyacrylamide gel matrix, and the resulting cell column was perifused with a physiological buffer. The secretion of ANF immunoactivity was markedly stimulated by increases in extracellular osmolality, regardless of the solute (NaCl, KCl, or glucose). This effect did not require extracellular Ca2+, nor could it be mimicked by depolarizing concentrations of K+ in an isotonic medium. Functional viability of this model was demonstrated by significant dose-related increases in ANF release in response to as little as 1 nM epinephrine. The dissociation of ANF secretion from depolarization-induced changes in Ca2+ flux is unusual and may represent an adaptation to the dual roles of the atrial myocyte, contraction and secretion.

Animals↗

Involvement of a cholinergic mechanism in the sustained depolarization and contraction of the lower oesophageal sphincter muscle cells in the cat.

Membrane potentials were recorded in vitro with intracellular electrodes from the circular muscle cells of the cat lower oesophageal sphincter and oesophageal body. In addition, the tension of lower oesophageal sphincter and oesophageal body strips was recorded isotonically. Under the experimental conditions, no spontaneous electrical activity or variation in the tension of the strips occurred. The resting membrane potential of the circular muscle cells was significantly lower in the lower oesophageal sphincter (-51.0 +/- 0.3 mV) than in the circular muscle cells of the oesophageal body (-57.1 +/- 0.4 mV). These values were not affected by infusion of tetrodotoxin 3.1 x 10(-6) M. In the presence of atropine (3.5 x 10(-7) M), the resting membrane potential of the circular muscle cells of the lower oesophageal sphincter increased significantly (-57.6 +/- 0.4 mV), whereas the resting membrane potential of the circular muscle cells of the oesophageal body was not significantly affected (-57.8 +/- 0.6 mV). In the presence of atropine, no significant difference in the values of the resting membrane potential of the circular muscle cells was observed between the lower oesophageal sphincter and the oesophageal body. Hyoscine (2.9 x 10(-7) M) significantly increased the resting membrane potential of the circular muscle cells of the lower oesophageal sphincter, whereas eserine (3.6 x 10(-6) M) significantly decreased it. Atropine induced a significant decrease in the membrane resistance of the circular muscle cells of the lower oesophageal sphincter. Atropine decreased the resting tension of lower oesophageal sphincter strips whereas eserine increased it, but no such effects were recorded on oesophageal body strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro and in vivo survival of cryopreserved sheep embryos.

Experiments were conducted to devise an efficient method to cryopreserve ovine embryos for field application. Embryos were surgically collected from superovulated ewes on Day 6 after natural breeding; oocytes were collected from ovaries obtained at the abattoir. Osmotic behavior of oocytes and embryos was determined by measuring their responses to hypertonic solutions of CsCl or sucrose. Embryos and oocytes contracted osmotically by decreasing their volumes proportionally to the reciprocal of the solution's osmolality. The respective nonosmotic volumes of embryos in CsCl and sucrose were 13.8 and 13.5% of their isotonic volume, and those of oocytes were 18.5 and 19.6%. Tests of the permeability of morulae to commonly used cryoprotectants, ethylene glycol (EG), propylene glycol (PG), dimethyl sulfoxide (DMSO), and glycerol (Glyc), showed that the order of permeability was EG > PG > DMSO approximately Glyc. Comparison of the efficacy of cryoprotective agents indicated that the respective survivals of embryos frozen in EG, PG, and DMSO were 76.9, 62.5, and 55.6%, based on their development into hatched blastocysts in vitro. Therefore, EG appeared to be superior to the other two cryoprotectants for freezing sheep embryos. To determine the functional survival of embryos in vivo, 67 embryos frozen in EG were thawed and directly diluted with phosphate-buffered saline; 47 of these (70%) appeared morphologically normal and were transferred into 14 recipients. Five of these recipients, which had received a total of 16 embryos, became pregnant. Ten lambs were born, showing that the method employed in this study for cryopreservation of sheep embryos followed by their direct dilution out of EG has potential application for practical field use.

Animals↗

Effect of composition of gastric contents on resistance to emptying of liquids from stomach in humans.

Experiments were conducted in normal healthy volunteers to investigate whether factors other than the intragastric pressure induced by tonic contraction of the gastric fundus could regulate the gastric emptying of liquids. The emptying of solutions of different osmolality and composition from the stomach was measured, while maintaining the intragastric pressure constant with a barostat system that employed an external reservoir. Preliminary experiments showed a linear relationship between intragastric pressure and emptying rate, but indicated that a normal intragastric pressure of 7 cm water would be insufficient by itself to maintain normal emptying. When intragastric pressure was maintained at 20 cm water, an isotonic solution of 30 mM glucose in saline (278 mosm/kg) emptied at a rate of 49.9 +/- 0.5 ml/min (mean +/- SEM, N = 11). Milk (284 mosm/kg) and a hyperosmolar solution of 30 mM glucose in saline (586 mosm/kg) significantly reduced the emptying rate. These results suggest that factors other than the intragastric pressure induced by fundic contraction regulate the rate at which liquids empty from the stomach and that the slower emptying of hyperosmotic solutions or solutions containing fat could be brought about in part either by an increased resistance of the pylorus and possibly the duodenum or a reduction in the effectiveness of an antroduodenal pump.

Adolescent↗

Myocardial mechanics predict hemodynamic performance during normal function and alcohol-induced dysfunction in rats.

To determine whether mechanical evaluation of muscle tissue removed from the myocardium can be employed as a direct indicator of cardiac contractile performance in situ, isometric and isotonic parameters of muscle mechanics in vitro were correlated with in vivo global functional characteristics of the same heart. Twelve-month-old animals maintained on standard food and water were employed as representative of normal cardiac function. Animals of identical age with left ventricular (LV) dysfunction induced by oral alcohol (30%) ingestion from 4 to 12 mo were utilized to represent depressed cardiac performance. Accordingly, 24 h after the establishment of the hemodynamic profile for a control or experimental heart, the LV posterior papillary muscle was removed from the same heart and examined isometrically and isotonically. Least squares regression analysis was employed to establish a correlation coefficient and P values between various in vitro and in vivo parameters. Hemodynamic measurements were performed under chloral hydrate anesthesia and LV pump performance was evaluated with respect to aortic and ventricular pressures and the rates of rise and decay of the LV pressure trace. Papillary muscles were evaluated with respect to timing parameters of the isometric and isotonic twitch, the first derivative of isometric tension development, and the speed of muscle shortening at increasing physiologic loads. LV peak rate of pressure rise and decay were then correlated with the various isometric and isotonic properties. Myocardial mechanics and hemodynamics revealed depressed function in the papillary muscles and hearts from alcoholic rats. Moreover, significant correlations were found between the LV rate of pressure change (peak +dP/dt and -dP/dt) and both isometric and isotonic twitch measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Embryonal reduction using transvaginal saline injection in a sextuplet pregnancy after ovulation induction with human menopausal gonadotropin.

A sextuplet pregnancy occurred in a first treatment cycle of ovulation induction with human menopausal gonadotropins. The serum 17-beta-estradiol concentration was 1245 pg/ml on the day of human chorionic gonadotropin administration. Embryonal reduction of four fetuses was carried out at nine weeks gestation using a transvaginal ultrasound-guided approach. Under general anesthesia, a 16-gauge in vitro fertilization needle was introduced through the posterior fornix and uterine wall, into the nearest gestational sac. The embryo was penetrated and 0.9% saline solution was injected until disintegration was noted, and confirmed by a lack of pulse for more than two minutes. The same procedure was applied to the three embryos in closest proximity to the needle. The patient delivered healthy twins in the 34th week of gestation after having had pre-term contractions for two weeks.

Abortion, Induced↗

A dynamic model of smooth muscle contraction.

A dynamic model of smooth muscle contraction is presented and is compared with the mechanical properties of vascular smooth muscle in the rat portal vein. The model is based on the sliding filament theory and the assumption that force is produced by cross-bridges extending from the myosin to the actin filaments. Thus, the fundamental aspects of the model are also potentially applicable to skeletal muscle. The main concept of the model is that the transfer of energy via the cross-bridges can be described as a 'friction clutch' mechanism. It is shown that a mathematical formulation of this concept gives rise to a model that agrees well with experimental observations on smooth muscle mechanics under isotonic as well as isometric conditions. It is noted that the model, without any ad hoc assumptions, displays a nonhyperbolic force-velocity relationship in its high-force portion and that it is able to maintain isometric force in conditions of reduced maximum contraction velocity. Both these findings are consistent with new experimental observations on smooth muscle mechanics cannot be accounted for by the classical Hill model.

Animals↗

Sliding distance per ATP molecule hydrolyzed by myosin heads during isotonic shortening of skinned muscle fibers.

We measured isotonic sliding distance of single skinned fibers from rabbit psoas muscle when known and limited amounts of ATP were made available to the contractile apparatus. The fibers were immersed in paraffin oil at 20 degrees C, and laser pulse photolysis of caged ATP within the fiber initiated the contraction. The amount of ATP released was measured by photolyzing 3H-ATP within fibers, separating the reaction products by high-pressure liquid chromatography, and then counting the effluent peaks by liquid scintillation. The fiber stiffness was monitored to estimate the proportion of thick and thin filament sites interacting during filament sliding. The interaction distance, Di, defined as the sliding distance while a myosin head interacts with actin in the thin filament per ATP molecule hydrolyzed, was estimated from the shortening distance, the number of ATP molecules hydrolyzed by the myosin heads, and the stiffness. Di increased from 11 to 60 nm as the isotonic tension was reduced from 80% to 6% of the isometric tension. Velocity and Di increased with the concentration of ATP available. As isotonic load was increased, the interaction distance decreased linearly with decrease of the shortening velocity and extrapolated to 8 nm at zero velocity. Extrapolation of the relationship between Di and velocity to saturating ATP concentration suggests that Di reaches 100-190 nm at high shortening velocity. The interaction distance corresponds to the sliding distance while cross-bridges are producing positive (working) force plus the distance while they are dragging (producing negative forces). The results indicate that the working and drag distances increase as the velocity increases. Because Di is larger than the size of either the myosin head or the actin monomer, the results suggest that for each ATPase cycle, a myosin head interacts mechanically with several actin monomers either while working or while producing drag.

Adenosine Diphosphate↗

Reduced unloaded sarcomere shortening velocity and a shift to a slower myosin isoform in acute murine coxsackievirus myocarditis.

We developed a mouse myocardial preparation to study cellular dysfunction in acute coxsackievirus myocarditis. Thin right ventricular papillary muscles from normal mice (n = 8) were compared with muscles from mice 7 days after coxsackievirus infection (n = 7). Sarcomere shortening was studied with laser diffraction (HeNe, lambda = 623.8 nm). A servomotor was used to shorten a muscle until slack early in isometric contraction. Unloaded sarcomere shortening velocity (Vo) was measured at the start of zero force at slack length. Vo was independent of the extent of slack release and was the same as that estimated with an isotonic force-sarcomere shortening velocity relation. Resting muscle stiffness was calculated from shortening perturbations in resting muscles. The histology of some papillary muscles (normal, n = 4; infected, n = 3) was studied. There was no ventricular hypertrophy. Resting sarcomere length (SL) in infected preparations (2.11 +/- 0.07 micron) (mean +/- 1 SD) was the same as in normal preparations (2.11 +/- 0.08 micron). In isometric twitches in normal and infected muscles, total peak force (4.31 +/- 1.07 and 3.77 +/- 1.86 g/mm2, respectively) resting force (0.81 +/- 0.37 and 0.81 +/- 0.35 g/mm2, respectively), and time to peak force (129.5 +/- 20.3 and 125.2 +/- 13.0 milliseconds, respectively) were not significantly different. Vo was 4.14 +/- 0.84 micron/s in normal muscles at an SL of 2.08 +/- 0.09 micron and 1.70 +/- 0.33 micron/s in infected muscles at an SL of 2.06 +/- 0.08 micron. Resting stiffness was the same for normal and infected muscles. There was inflammation but no fibrosis or necrosis. Thus, Vo was depressed early in acute viral myocarditis without hypertrophy, myocyte necrosis, fibrosis, or altered resting stiffness. Pyrophosphate gel electrophoresis showed a shift from predominantly fast to slow myosin isoforms. Apparently, there is remodeling of the contractile apparatus early in acute coxsackievirus myocarditis that is caused either by the direct effects of the virus or the immune response.

Animals↗

Central fatigue as revealed by postexercise decrement of motor evoked potentials.

We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement in amplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS delivered at the rates of 0.1, 0.15, 0.3, 1, 3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue.

Adult↗

Cardiac energetics in short and long term hypertrophy induced by aortic coarctation.

Hypertrophy was induced in rats by constriction of the abdominal aorta proximal to the coeliac trunk. The effects of both short-term, STH. (2 to 4 days) and long term, LTH (40 to 55 days) hypertrophy were studied by mechanical and myothermic measurements on papillary muscles from the left ventricle. In agreement with other studies aortic coarctation increased the left ventricle to body weight ratio. In isometric experiments it was shown that peak stress development was enhanced in the STH group compared with the control and LTH groups. Active heat production was related to active stress development by linear regression in the control and pressure overload groups. There was no significant difference between the mean slopes of the groups but there was a significant increase in the intercept in the STH group and a decrease in the LTH group. This intercept corresponds to the tension-independent heat component. In isotonic experiments load enthalpy relationships were determined for the different groups and the data for each group were pooled. In the LTH group there was a 19% fall in work output per contraction and a 20% fall in total enthalpy. In the STH group there was a 31% increase in work output and a 39% rise in total enthalpy. Because of the parallel changes in work and enthalpy there was no significant change in the mechanical efficiency of the two groups as compared to the controls. The simplest interpretation of the results is that in STH the intracellular free calcium level is raised whereas in LTH it is lowered.

Animals↗