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PubMed1985

Changes in isometric contractile properties of extensor digitorum longus and soleus muscles of C57BL/6J mice following denervation.

In this study, conducted on mice of the C57BL/6J+/+ strain, we investigated the differential effects of denervation on the isometric contractile properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles. The contractile properties were studied at 1, 28, 84, and 210 days following unilateral section of the sciatic nerve at 12 weeks of age. When isometric tetanus tension was expressed relative to wet weight, the denervated SOL showed an earlier and more pronounced loss in tension generating capacity than the EDL. Both the denervated SOL and EDL showed potentiation of the twitch tension at 28 days postdenervation. The time to peak twitch tension (TTP) and the time to half-relaxation (1/2RT) were prolonged by 28 days postdenervation in both muscles. This trend continued to the oldest age-groups studied in the EDL, but reached an apparent plateau in the SOL at 84 days postdenervation. In response to fatigue, the denervated SOL showed a marked decrease in resistance to fatigue at 1 day but a relatively normal response thereafter, whereas the denervated EDL showed an increase in resistance to fatigue at and beyond the 28-day period. In spite of the fact that the total contraction time of both muscles increased following denervation, the predominantly oxidative SOL remained a slower contracting muscle than the more glycolytic EDL.

Animals↗

PubMed1978

Dynamic stiffness of rabbit mesotubarium smooth muscle: effect of isometric length.

The dynamic stiffness of mesotubarium smooth muscle from nonpregnant adult rabbits was measured continuously during isometric contraction by applying small (0.5 percent of the muscle length) sinusoidal length perturbations and measuring the amplitude and phase of the resulting tension perturbations. Stiffness during contraction was directly proportional to muscle tension; during relaxation stiffness at all tensions was significantly increased as compared to the values encountered during the rise of tension. Peak isometric tension and dynamic stiffness (determined at a common tension level) both decreased at shorter muscle lengths; the relative falloff in stiffness was significantly less than the tension decrease. Varying levels of muscle activation (obtained by changing stimulus strength and by applying quick releases to active muscle) had little effect on the measured elastic modulus. Comparisons of these results with published data on single-cell contractile properties imply a cellular locus for a portion of the measured stiffness.

Animals↗

PubMed1986

Effects of forskolin and cyclic nucleotides on isometric force in rat aorta.

The present study was undertaken to determine the extent to which cyclic nucleotide-induced relaxation in the intact rat aorta is mediated at the level of the contractile system. The relaxant effects of the cyclic nucleotide analogues [8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP)] and forskolin were examined in both the intact vessel and a Triton X-100-skinned preparation of rat thoracic aorta. Relaxation of a norepinephrine-induced contraction was essentially complete 30 min after the addition of 50 microM 8-BrcGMP [% relaxation = 87.2 +/- 4.4% (n = 4)], 100 microM DBcAMP [98.2 +/- 1.2% (n = 4)], and 1 microM forskolin [107.0 +/- 3.3% (n = 5)]. These same doses were ineffective in relaxing precontracted skinned rat aortic rings compared with the relaxation achieved in the intact vessel. The largest relaxation in the skinned aortas was achieved with the addition of 1 microM forskolin [17.4 +/- 1.5% (n = 4)]. The addition of catalytic subunit of cAMP-dependent protein kinase had no effect on isometric tension in the precontracted skinned aorta. Preincubation with the cyclic nucleotide analogues or forskolin in a low-Ca2+ solution (pCa less than 8) was also ineffective in inhibiting subsequent isometric tension development. Our results suggest that only a very small fraction of the relaxation with cyclic nucleotides and forskolin in the intact rat aorta is due to the action of these agents at the level of the contractile system.

Animals↗

PubMed1988

G-1,6-P2 in human skeletal muscle after isometric contraction.

The content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of phosphofructokinase (a rate-limiting enzyme for glycolysis), and the glycolytic rate in skeletal muscle during isometric contraction have been determined. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue. Biopsies from the quadriceps femoris muscle were obtained before and immediately after contraction. G-1,6-P2 increased in all subjects from a mean of 101 +/- 15 (SE) mumol/kg dry wt at rest to 128 +/- 24 at fatigue (P less than 0.05). Muscle glucose did not change significantly, whereas hexosemonophosphates were significantly increased after contraction. The glycogenolytic and glycolytic rate averaged 70.0 +/- 13.8 and 47.3 +/- 6.7 mmol.kg dry wt-1.min-1, respectively, and the glycolytic rate was positively correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r = 0.95, P less than 0.01) and G-6-P (r = 0.96, P less than 0.01). Phosphocreatine and ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31% after contraction. These data demonstrate that intense, short-term isometric contraction results in an elevation of the muscle content of G-1,6-P2. The increase in G-1,6-P2 could not be accounted for by the side reactions of phosphoglucomutase or phosphofructokinase. It remains to be determined whether the observed increase in G-1,6-P2 is sufficient to account for the high glycolytic rate during intense exercise. The lack of increase in muscle glucose while G-6-P increased (which will inhibit hexokinase) suggests that the debranching enzyme complex was not active during contraction.

Adenine Nucleotides↗

PubMed1988

Heat production of rat anococcygeus muscle during isometric contraction.

Heat production, unloaded shortening velocity (Vus), and load-bearing capacity (LBC) were studied in the isolated rat anococcygeus muscle during isometric contractions at 27 degrees C. The relation between the total suprabasal heat produced and the stress-time integral for isometric contractions of various durations was curvilinear, demonstrating a decreasing slope as contractile duration increased. The rate of heat production at 600 s was approximately 68% of the peak value of 6.55 mW/g that occurred at 10 s. At the same time, force rose from a mean of 92 mN/mm2 at 10 s to a value of 140 mN/mm2 at 600 s. This produced a nearly threefold increase in the economy of force maintenance. The decline in the rate of heat production was accompanied by a decline in Vus from 0.56 Lo/s at 10 s to 0.28 Lo/s at 600 s, where Lo is the length for optimal force development. This suggests the fall in the rate of heat production was caused, at least in part, by a slowing of cross-bridge kinetics. The ratio of LBC to developed tension at 10 s was not significantly different from the ratio at 600 s, suggesting that the increase in tension was due to an increased number of attached cross bridges. The decline in heat production, therefore, appears contradictory, since an increased number of attached cross bridges would predict an increased rate of energy expenditure. The observations can be reconciled if either 1) the increase in force is caused by a progressive increase in the attachment time of a constant number of cross bridges that cycle at a lower frequency or 2) the decline in energy expenditure caused by the slowing of cross-bridge cycling is sufficient to mask the increase caused by the recruitment of additional cross bridges.

Animals↗

PubMed1992

Effect of fatigue on rate of isometric force development in mouse fast- and slow-twitch muscles.

Changes in the rate of isometric force development with fatigue were measured in vitro (25 degrees C) using mouse soleus and extensor digitorum longus (EDL) muscles. Muscles were fatigued using 30 tetanic contractions. Rate of force development was determined from the rate constant of an exponential curve fitted to the rising force phase of a tetanus. For both muscles, when the intertetanus interval was 3 s, maximum isometric force and relaxation rate were significantly reduced in the final tetanus relative to the values in the first tetanus. Rate of force development in soleus muscles transiently increased and then decreased a small amount. The final rate was 92.7 +/- 3.3% (n = 4) of the initial rate. In contrast, the rate of force development in EDL muscles increased to 133.7 +/- 3.3% (n = 4) of the initial rate. This increased rate was evident from the second tetanus of the series, was fully established after 5 tetani, and the magnitude of the increase in rate was inversely proportional to intertetanus interval and was independent of presumed energy expenditure. The enhanced rate decayed with a time constant of 14.3 +/- 2.0 s and was independent of presumed energy expenditure. Most of these observations can be explained by the effects of P(i) on cross bridge kinetics. Other possible mechanisms, involving more rapid activation, are also suggested.

Animals↗

PubMed2005

Time-dependent modulation of arterial baroreflex control of muscle sympathetic nerve activity during isometric exercise in humans.

We investigated the time-dependent modulation of arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) that occurs during isometric handgrip exercise (IHG). Thirteen healthy subjects performed a 3-min IHG at 30% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between spontaneous variations in diastolic arterial pressure (DAP) and MSNA during supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear relations between DAP and MSNA variables were shifted progressively rightward until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA relations were shifted upward and were shifted further upward at IHG3; 3) the sensitivity of the ABR control of total MSNA was increased at IHG2 and increased further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly higher than at IHG2, and the sensitivity of the control of total MSNA was the same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP-burst incidence relation remained at the IHG3 level. These results indicate that during IHG, ABR control of MSNA is modulated in a time-dependent manner. We suggest that this modulation of ABR function is one of the mechanisms underlying the progressive increase in blood pressure and MSNA during the course of isometric exercise.

Adaptation, Physiological↗

PubMed2004

Single cell mechanics of rat cardiomyocytes under isometric, unloaded, and physiologically loaded conditions.

One of the most salient characteristics of the heart is its ability to adjust work output to external load. To examine whether a single cardiomyocyte preparation retains this property, we measured the contractile function of a single rat cardiomyocyte under a wide range of loading conditions using a force-length measurement system implemented with adaptive control. A pair of carbon fibers was used to clamp the cardiomyocyte, attached to each end under a microscope. One fiber was stiff, serving as a mechanical anchor, while the bending motion of the compliant fiber was monitored for force-length measurement. Furthermore, by controlling the position of the compliant fiber using a piezoelectric translator based on adaptive control, we could change load dynamically during contractions. Under unloaded conditions, maximal shortening velocity was 106 +/- 8.9 microm/s (n = 13 cells), and, under isometric conditions, peak developed force reached 5,720 nN (41.6 +/- 5.6 mN/mm(2); n = 17 cells). When we simulated physiological working conditions consisting of an isometric contraction, followed by shortening and relaxation, the average work output was 828 +/- 123 J/m(3) (n = 20 cells). The top left corners of tension-length loops obtained under all of these conditions approximate a line, analogous to the end-systolic pressure-volume relation of the ventricle. All of the functional characteristics described were analogous to those established by studies using papillary muscle or trabeculae preparations. In conclusion, the present results confirmed the fact that each myocyte forms the functional basis for ventricular function and that single cell mechanics can be a link between subcellular events and ventricular mechanics.

Animals↗

PubMed1989

Analysis of myocardial isometric dynamics using parameters of a global model.

Despite previous efforts, a global empirical relation has not been described for the myocardial isometric curve, F(t). We propose here that a useful relation is F(t) = CtB-1e-AtB. A, B, and C are global parameters. We evaluated this model and the effect of change in muscle length (L) and dobutamine on the parameters in nine in situ canine papillary muscles. A servo-system clamped muscle length to produce isometric twitches. For each twitch, the parameters were determined by curve fitting. The model fit the observed curves of F(t) closely; the correlation coefficient was 0.997 +/- 0.001. Whereas C changed with L, A and especially B varied little with L averaging 28.6 +/- 5.2 and 2.42 +/- 0.08, respectively. Our predictions that A reflects chronotropic state, B lusitropic, and C heterometric and inotropic states, were verified with dobutamine. We also derived relations for various attributes of the F(t) curve in terms of A, B, and C only. An excellent correlation was noted between the calculated and the observed values of these attributes. The empirical relation F(t) = CtB-1e-AtB therefore provides a valid cohesive reference frame for analysis of myocardial dynamics.

Animals↗

PubMed1990

Reflex responses of renal nerve activity during isometric muscle contraction in cats.

Renal sympathetic nerve activity (RSNA), arterial blood pressure (AP), and heart rate (HR) were measured during isometric muscle contraction of a hindlimb in chloralose-anesthetized cats. In 14 cats RSNA, AP, and HR increased during a 1-min contraction by 45%, 39 mmHg, and 11 beats/min, respectively; however, in three cats there was a brief initial decrease in RSNA followed by an increase. In 11 cats isometric contraction was maintained for 5 min by alternate stimulation of the L7 and S1 ventral roots. In the first 1 min of sustained contraction, there was a positive correlation (gamma = 0.58, P less than 0.005) between RSNA and tension development. Thereafter RSNA remained elevated despite a tension decrease, and there was no significant correlation between these changes. The RSNA response to contraction of both hindlimbs was greater than that to contraction of either hindlimb alone. Passive stretch of the hindlimb muscle significantly increased RSNA. Thus the initial increase in RSNA during sustained contraction is likely due to activation of muscle mechanoreceptors, whereas the later increase is probably caused by activation of the muscle metaboreceptors.

Animals↗

PubMed1991

Global analysis of myocardial isotonic shortening: comparison with isometric dynamics.

Although potentially analytically useful, a global empirical model of the myocardial isotonic curve, L(t), has not been described. We propose the following relation: L(t) = C(t/A)B-1e-(t/A)B, where A, B, and C are global parameters, L is length, and t is time. We evaluated this model in nine in situ canine papillary muscles studied with a servo-system to produce isotonic twitches at different isotonic forces (F). For each twitch, the parameters were determined by nonlinear curve fitting. The model fit the observed curves of L(t) closely, with the coefficient of determination being 0.995 +/- 0.002. C changed with F, but A and B varied little with F, averaging 0.262 +/- 0.021 s and 2.76 +/- 0.17, respectively. Our predictions that A reflects chronotropic, B reflects lusitropic, and C reflects heterotonic (different afterloads) and inotropic states were supported. Comparison done in five muscles showed that A was the same but B was higher for isotonic than for isometric twitches: 0.270 +/- 0.020 vs. 0.264 +/- 0.038 s (P = not significant) for A and 2.79 +/- 0.18 vs. 2.39 +/- 0.05 (P less than 0.008) for B. Dobutamine increased A but not B in isotonic twitches. Thus shortening is lusitropic but leaves no lusitropic reserve to be mobilized by dobutamine. The relation L(t) = C(t/A)B-1e-(t/A)B provides a framework that undergirds global analysis of myocardial shortening and enables comparison with isometric dynamics.

Animals↗

PubMed1992

Isometric biaxial tension of smooth muscle in isolated cylindrical segments of rabbit arteries.

Biaxial tension developed in the common carotid and femoral arteries of rabbits by the activation of smooth muscle was determined in vitro using cylindrical segments. While the smooth muscle was stimulated with 10(-5) M norepinephrine, the intraluminal pressure and axial force were measured under isometric conditions, i.e., keeping the diameter and length constant. The development of the active tension in the axial direction was roughly proportional to that in the circumferential direction. The ratio of the axial stress response to the circumferential one was positively correlated to the ratio of the axial stretch to the circumferential one. The axial response was larger than expected from the histological observation that the smooth muscle cells align almost circumferentially. This means that although smooth muscle cells are oriented almost circumferentially, the extracellular matrix transmitted the smooth muscle constriction force not only in the circumferential direction, but also in the longitudinal direction under isometric conditions.

Animals↗

PubMed1994

Preload, length-tension relation, and isometric relaxation in cardiac muscle.

It is widely believed that preload does not influence isometric relaxation and left ventricular pressure fall. Preload, however, alters cross-bridge interaction and intracellular Ca2+ handling. We therefore evaluated the effects of preload reduction on peak length-tension relation and on physiologically sequences isometric force decline. 1) Acute preload reduction resulted in a shift to the left of the peak length-tension relation, an earlier onset of force decline, and an increased rate of initial force decline. 2) Prolonged preload reduction was compared with acute preload reduction and resulted in an unchanged peak length-tension relation, a delayed onset of force decline, and a decreased initial rate of force decline. 3) Prolonged preload reduction was compared with baseline and resulted in a shift to the left of the peak length-tension relation, without predictable effects on timing or rate of force decline. Our hypothesis is that the findings reflected both changes in troponin C affinity for Ca2+ and altered Ca2+ reuptake by the sarcoplasmic reticulum.

Animals↗

PubMed1997

Stimulated neutrophils induce myosin light chain phosphorylation and isometric tension in endothelial cells.

The mechanism or mechanisms by which polymorphonuclear leukocytes (PMN) penetrate junctions between neighboring endothelial cells (EC) to traverse endothelial barriers remain unresolved. We report that chemoattractant-stimulated PMN induce a coordinate increase in both phosphorylation of serine 19 and threonine 18 of EC myosin regulatory light chains and isometric tension generation by EC monolayers. Unstimulated PMN had no effect on either parameter. These findings, coupled with our previous report (Huang et al., J. Cell Biol. 120: 1371-1380, 1993) that chemoattractant-stimulated PMN cause a rise in EC cytosolic free Ca2+, provide strong presumptive evidence that myosin light chain kinase is the EC enzyme responsible for initiating myosin light chain phosphorylation, EC contraction, and isometric tension generation in response to chemoattractant-stimulated PMN. We suggest that, by inducing phosphorylation of EC cytoskeletal proteins, chemoattractant-stimulated PMN induce EC to open their intercellular junctions, thereby facilitating transendothelial movement of these leukocytes.

Chemotactic Factors↗

PubMed1998

Human carotid baroreflex during isometric lower arm contraction and ischemia.

Our aim was to determine the roles of somatomotor activation and muscle ischemia for the tachycardia and hypertension of isometric arm contraction. Carotid-cardiac and carotid-mean arterial pressure (MAP) baroreflex response curves were determined in 10 men during rest, during isometric arm contraction at 30% of maximum, and during postcontraction ischemia. Carotid distending pressure (CDP) was changed by applying pressure and suction in a neck chamber. Pressures ranged from +40 to -80 mmHg and were applied repeatedly for 15 s during the three conditions. Maximum slopes and ranges of the response curves did not differ among conditions. The heart rate (HR) curve was shifted to a 14 +/- 1.8 (mean +/- SE) beats/min higher HR and a 9 +/- 5.7 mmHg higher CDP during contraction and to a 14 +/- 5.9 mmHg higher CDP during postcontraction ischemia with no change of HR compared with rest. The MAP curve was shifted to a 20 +/- 2.8 mmHg higher MAP and to a 18 +/- 5.4 mmHg higher CDP during contraction, and the same shifts were recorded during postcontraction ischemia. We conclude that neither somatomotor activation nor muscle ischemia changes the sensitivity of arterial baroreflexes. The upward shift of the MAP response curve, with no shift of the HR response curve during postexercise ischemia, supports the notion of parallel pathways for MAP and HR regulation in which HR responses are entirely caused by somatomotor activation and the pressor response is mainly caused by muscle ischemia.

Adult↗

PubMed1991

Excitatory pathways in smooth muscle investigated by phase-plot analysis of isometric force development.

Excitatory pathways in the smooth muscle of the pig urinary bladder were investigated using phase-plot analysis of isometric contractions. The phase plots, plots of the rate of change of the force as a function of the force itself, were dominated by a straight line described by the horizontal intercept (Fiso) and the vertical intercept (U). The quotient Fiso/U is a time constant that characterizes the rate-limiting step in isometric force development in the muscle. Bladder strips of 1 mm diameter were activated by electrical field stimuli, acetylcholine, potassium, and ATP in combination with selective pathway inhibitors such as verapamil, atropine, or a calcium-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When pathways that depended significantly on depolarization or intracellular calcium release were selected, the time constant was significantly smaller, indicating a faster process. The results indicated that the rate-limiting step in force development was determined by the influx of extracellular calcium.

Animals↗

PubMed1991

Sympathoadrenal-circulatory regulation during sustained isometric exercise in young and older men.

The aim of this study was to test the hypothesis that the arterial blood pressure, vasoconstrictor, and sympathoadrenal adjustments to sustained submaximal isometric exercise become augmented with advancing age in humans. Fourteen young (26 +/- 1 yr) and 14 older (66 +/- 1 yr) healthy males performed isometric handgrip exercise at 30% of maximal voluntary force until exhaustion (inability to maintain target force). Maximal handgrip force was quite similar in the young and older subjects (402 +/- 20 vs. 392 +/- 20 N, respectively). The two groups did not differ significantly on any variable at rest. During sustained handgrip to exhaustion, peak levels of both perceived exertion and contracting forearm electromyographic activity were similar in the young and older men, suggesting equivalent voluntary efforts. Exercise time was not different in the two groups (315 +/- 27 s in young vs. 339 +/- 17 s in older men). Throughout exercise the increases in arterial blood pressure were very similar in the young and older subjects. Heart rate increased less (P less than 0.05), but stroke volume (impedance cardiography) tended to decrease less (not significant) in the older men; thus the increases in cardiac output were not different in the two groups. During the latter portion of exercise, systemic vascular resistance tended to increase in both the young and older men, with no significant group differences. The blood flow responses in the whole calf (venous occlusion plethysmography) and the calf skin (laser-Doppler velocimetry) were similar in the young and older subjects, as were the corresponding increases in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1981

Blood flow and metabolism during isometric contractions in cat skeletal muscle.

The muscle blood flow, oxygen uptake, carbon dioxide production, muscle and blood lactate, muscle ATP, creatinine phosphate, glycogen, and venous pH were measured in the soleus (a slow-twitch muscle) and the medial gastrocnemius (a fast-twitch muscle) of the cat during fatiguing isometric exercise. Five tensions were examined: 10, 25, 50, 75, and 100% of the initial strength of the muscles (tetanic tension of the unfatigued muscle). Contractions were either sustained to fatigue or, for tensions of 10 and 25% initial strength of the soleus muscle, were sustained for 3 min. Analysis of the blood flow and metabolites from these muscles showed that the soleus was heavily dependent on its blood supply, using aerobic metabolism as the predominant pathway, whereas the medial gastrocnemius muscle seemed to use anaerobic metabolism even at low isometric tensions.

Adenosine Triphosphate↗