Muscle blood flow during isometric activity and its relation to muscle fatigue

The effect of isometric exercise on blood flow, blood pressure, intramuscular pressure as well as lactate and potassium efflux from exercising muscle was examined. The contractions performed were continuous or intermittent (5 s on, 5 s off) and varied between 5% and 50% maximal voluntary contraction (MVC). A knee-extensor and a hand-grip protocol were used. Evidence is presented that blood flow through the muscle is sufficient during low-level sustained contractions (less than 10% MVC). Despite this muscle fatigue occurs during prolonged contractions. One mechanism for this fatigue may be the disturbance of the potassium homeostasis. Such changes may also play a role in the development of fatigue during intermittent isometric contractions and even more so in the recovery from such exercise. In addition the role of impaired transport of substances within the muscle, due to long-lasting daily oedema formation, is discussed in relation to fatigue in highly repetitive, monotonous jobs.     

Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle

Rat extensor digitorum longus muscleswere overloaded by stretch after removal of the synergist tibialisanterior muscle to determine the relationship between capillary growth,muscle blood flow, and presence of growth factors. After 2 wk,sarcomere length increased from 2.4 to 2.9 µm. Capillary-to-fiberratio, estimated from alkaline phosphatase-stained frozen sections, wasincreased by 33% (P < 0.0001) and60% (P < 0.01), compared withcontrol muscles (1.44 ± 0.06) after 2 and 8 wk, respectively. At 2 wk, the increased capillary-to-fiber ratio was not associated with anychanges in mRNA for basic fibroblast growth factor (FGF-2) or itsprotein distribution. FGF-2 immunoreactivity was present in nerves andlarge blood vessels but was negative in capillaries, whereas theactivity of low-molecular endothelial-cell-stimulating angiogenicfactor (ESAF) was 50% higher in stretched muscles. Muscle blood flowsmeasured by radiolabeled microspheres during contractions were notsignificantly different after 2 or 8 wk (132 ± 37 and 177 ± 22 ml · min¹ · 100 g¹, respectively) fromweight-matched controls (156 ± 12 and 150 ± 10 ml · min¹ · 100 g¹, respectively).Resistance to fatigue during 5-min isometric contractions (final/peaktension × 100) was similar in 2-wk overloaded and contralateralmuscles (85 vs. 80%) and enhanced after 8 wk to 92%, compared with77% in contralateral muscles and 67% in controls. We conclude thatincreased blood flow cannot be responsible for initiating expansion ofthe capillary bed, nor does it explain the reduced fatigue withinoverloaded muscles. However, stretch can present a mechanical stimulusto capillary growth, acting either directly on the capillary abluminalsurface or by upregulating ESAF, but not FGF-2, in the extracellular matrix.

     

Exercise-induced injury to skeletal muscle

Strenuous or unaccustomed exercise can cause injury to skeletal muscle. This paper reviews our understanding of the mechanisms of exercise-induced injury. Measurements of exercise-induced injury have included muscle soreness, increased serum levels of intracellular enzymes, increased lysosomal enzyme activities, structural changes in muscle fibers, and prolonged decreases in force development that cannot be attributed to fatigue. Injury can be induced by exercise of small muscle groups, which suggests that it involves processes localized in skeletal muscles. Exercise of relatively short duration can result in injury, which indicates that long durations of exercise and associated metabolic changes are not necessary for injury to occur. Exercise that involves lengthening contractions results in greater evidence of muscle injury than exercise involving isometric or shortening contractions. Lengthening contractions are associated with higher levels of force and lower metabolic costs per muscle fiber than isometric or shortening contractions. These results suggest that changes in muscle metabolism are not responsible for exercise-induced injury to skeletal muscle. Exercise-induced injury is more likely the result of mechanical disruption of muscle fibers.     

Relationship of changes in diaphragmatic muscle blood flow to muscle contractile activity

The effect of increases in diaphragmatic muscle contractile activity on diaphragm blood flow remains unclear. The present study examined the effect of electrically induced isometric diaphragmatic muscle contractions on diaphragmatic blood flow. Studies were performed on diaphragmatic muscle strips prepared in anesthetized mechanically ventilated dogs. Diaphragmatic contractile activity was quantitated as the tension-time index (TTI) (i.e., the product of tension magnitude and duration). Blood flow to the strip (Qdi) was measured from the volume of the phrenic venous effluent using a drop counter. The separate effects on Qdi of 30-s periods of continuous and rhythmic contractions were examined. Qdi increased with increases in TTI and peaked at a TTI of 20-30% of maximum after which Qdi fell progressively with further increases in TTI. At levels of TTI greater than 30%, the pattern of muscle contraction significantly affected blood flow. Qdi was significantly lower during activity and the postcontraction hyperemia significantly greater at a given TTI when contractions were continuous than when contractions were intermittent. Above a TTI of 30%, Qdi during contraction decreased linearly with increases in duty cycle and curvilinearly with increases in tension. We conclude that during isometric diaphragmatic contractions, diaphragmatic blood flow may become mechanically impeded, and the magnitude of the impediment in blood flow depends on the pattern of diaphragmatic contractions. With increases in contractile activity above a critical level, changes in duty cycle exert progressively greater effects on diaphragmatic blood flow than changes in muscle tension.     

Exercise-induced cardiac hypertrophy: a correlation of blood flow and microvasculature

The effects of exercise conditioning on the myocardium were studied in seven instrumented pigs strenuously exercised for 12 wk by treadmill running. Data were compared with eight instrumented untrained pigs. O2 consumption measured during maximum exercise effort was significantly elevated in the trained pigs (71.7 +/- 4.0 vs. 56.3 +/- 3.0 ml X ml-1 X kg-1). Absolute right and left ventricular mass increased by 20 and 13%, respectively, in response to exercise. Myocyte cross-sectional area increased by 21% in the trained hearts compared with the untrained hearts. Transmural left ventricular myocardial blood flow (ml X min-1 X g-1) was not significantly different at rest, during maximum exercise, or during exercise with adenosine infusion. However, training caused an elevation of the regional epicardial blood flow noted during exercise and exercise with adenosine. In the trained pigs mean aortic pressure during maximum exercise with adenosine infusion was not significantly different compared with untrained pigs. Coronary resistance during exercise with adenosine infusion was the same in both animal groups. In the trained group capillary numerical (no./mm2) and length (mm/mm3) densities were reduced, whereas arteriolar numerical and length densities were significantly increased compared with the untrained group. Measurements of capillary luminal surface density (mm2/mm3) in the trained group were unchanged compared with the untrained group. These results suggest that strenuous exercise does not stimulate the production of new capillaries, but this is modified by the ability of existing capillaries to increase their luminal surface area to parallel increases in myocyte growth. The arteriolar data suggest that exercise promotes the formation of new arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation heat and latency relaxation in relation to calcium movement in skeletal and cardiac muscle

Measurements of activation heat, initial heat, twitch tension, and latency relaxation were made using thin-layer, vacuum-deposited thermopiles and isometric force transducers, respectively. Experiments were performed on frog skeletal muscle fiber bundles and on rabbit right ventricular papillary muscles at 0, 15, ans 21 degrees C in normal and 1.75X to 2.5X mannitol hyperosmotic bathing solutions. In skeletal muscle, activation heat, obtained by stretching to zero overlap, was only slightly affected by 1.75X hyperosmotic solution and consisted of a fast and a slow component. Both components have a refractory period and a relatively refractory period which can be demonstrated by double pulse stimulation. The twitch potentiators Zn2+ and caffeine increase the total activation heat and the magnitude and rate of the fast component. The temporal relation between the latency relaxation and activation heat is demonstrated. The latency relaxation is independent of the number of sarcomeres in series in a muscle. Activation heat and latency relaxation records from heart muscle are obtained in 2.5X hyperosmotic bathing solution. A model of excitation--contraction coupling is presented which indicates that (1) the downstroke of the latency relaxation monitors the functioning of the Ca2+-permeability or debinding mechanism in the terminal cisternae, (2) the fast component of activation heat monitors the amount of Ca2+ bound to troponin C, and (3) the total amplitude of activation heat is a measure of the total quantity of Ca2+ cycled in a twitch.     

Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake

It is not known whether the diameter of peripheral conduit arteries may impose a limitation on muscle blood flow and oxygen uptake at peak effort in humans, and it is not clear whether these arteries are dimensioned in relation to the tissue volume they supply or, rather, to the type and intensity of muscular activity. In this study, eight humans, with a peak pulmonary oxygen uptake of 3.90 +/- 0.31 (range 2.29-5.03) l/min during ergometer cycle exercise, performed one-legged dynamic knee extensor exercise up to peak effort at 68 +/- 7 W (range 55-100 W). Peak values for knee extensor blood flow (thermodilution) and oxygen uptake of 6.06 +/- 0.74 (range 4.75-9.52) l/min and 874 +/- 124 (range 590-1,521) ml/min, respectively, were achieved. Pulmonary oxygen uptake reached a peak of 1.72 +/- 0.19 (range 1.54-2.33) l/min. Diameters of common and profunda femoral arteries determined by ultrasound Doppler were 10.6 +/- 0.4 (range 8.2-12.7) and 6.0 +/- 0.4 (range 4.5-8.0) mm, respectively. Thigh and quadriceps muscle volume measured by computer tomography were 10.06 +/- 0.66 (range 6.18-10.95) and 2.36 +/- 0.19 (range 1.31-3.27) liters, respectively. The common femoral artery diameter, but not that of the profunda branch, correlated with the thigh volume and quadriceps muscle mass. There were no relationships between either of the diameters and the absolute or muscle mass-related resting and peak values of blood flow and oxygen uptake, peak pulmonary oxygen uptake, or peak power output during knee extensor exercise. However, common femoral artery diameter correlated to peak pulmonary oxygen uptake during ergometer cycle exercise. In conclusion, common and profunda femoral artery diameters are sufficient to ensure delivery to the quadriceps muscle. However, the common branch may impose a limitation during ergometer cycle exercise.     

Human muscle length-dependent changes in blood flow

Although a multitude of factors that influence skeletal muscle blood flow have been extensively investigated, the influence of muscle length on limb blood flow has received little attention. Thus the purpose of this investigation was to determine if cyclic changes in muscle length influence resting blood flow. Nine healthy men (28 ± 4 yr of age) underwent a passive knee extension protocol during which the subjects' knee joint was passively extended and flexed through 100-180° knee joint angle at a rate of 1 cycle per 30 s. Femoral blood flow, cardiac output (CO), heart rate (HR), stroke volume (SV), and mean arterial pressure (MAP) were continuously recorded during the entire protocol. These measurements revealed that slow passive changes in knee joint angle did not have a significant influence on HR, SV, MAP, or CO; however, net femoral blood flow demonstrated a curvilinear increase with knee joint angle (r(2) = 0.98) such that blood flow increased by ～90% (125 ml/min) across the 80° range of motion. This net change in blood flow was due to a constant antegrade blood flow across knee joint angle and negative relationship between retrograde blood flow and knee joint angle (r(2) = 0.98). Thus, despite the absence of central hemodynamic changes and local metabolic factors, blood flow to the leg was altered by changes in muscle length. Therefore, when designing research protocols, researchers need to be cognizant of the fact that joint angle, and ultimately muscle length, influence limb blood flow.     

Exercise-induced increase in muscle insulin sensitivity.

Exercise/muscle contraction activates glucose transport. The increase in muscle glucose transport induced by exercise is independent of insulin. As the acute effect of exercise on glucose transport wears off, it is replaced by an increase in insulin sensitivity. An increase in insulin sensitivity results in a shift in the insulin dose-response curve to the left, with a decrease in the concentration of insulin needed to induce 50% of the maximal response. This phenomenon, which plays a major role in rapid muscle glycogen accumulation after exercise, is not mediated by amplification of the insulin signal. Development of the increase in insulin sensitivity after contractions does not require protein synthesis or activation of p38 MAPK. It does require the presence of a serum protein during the period of contractile activity. The effect of exercise on muscle insulin sensitivity is mimicked by hypoxia and by treatment of muscles with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside to activate AMP-activated protein kinase. The postexercise increase in sensitivity of muscle glucose transport to activation is not specific for insulin but also involves an increased susceptibility to activation by a submaximal contraction/hypoxia stimulus. The increase in insulin sensitivity is mediated by translocation of more GLUT4 glucose transporters to the cell surface in response to a submaximal insulin stimulus. Although the postexercise increase in muscle insulin sensitivity has been characterized in considerable detail, the basic mechanisms underlying this phenomenon remain a mystery.     

Intramuscular pressure and muscle blood flow in supraspinatus

Intramuscular pressure and muscle blood flow was measured in the supraspinatus muscle in 6 healthy subjects. The recordings were performed at rest, during isometric exercise, during an isometric muscle contraction of 5.6 kPa (42 mm Hg) and 10.4 kPa (78 mm Hg) and at rest after the contraction. Intramuscular pressure was measured by the microcapillary infusion technique, and muscle blood flow by the Xenon-133 washout technique. Intramuscular pressure was 38.2 kPa (SD 12.0) (287 mm Hg) during maximal voluntary contraction. A muscle contraction pressure of 5.6 kPa (42 mm Hg), which is 16% of maximal voluntary contraction, reduces local muscle blood flow significantly. It is concluded that the high intramuscular pressures found in supraspinatus during work with the arms elevated impedes local muscle blood flow.     

A theory of blood flow in skeletal muscle

A theoretical analysis of blood flow in the microcirculation of skeletal muscle is provided. The flow in the microvessels of this organ is quasi steady and has a very low Reynolds number. The blood is non-Newtonian and the blood vessels are distensible with viscoelastic properties. A formulation of the problem is provided using a viscoelastic model for the vessel wall which was recently derived from measurements in the rat spinotrapezius muscle (Skalak and Schmid-Sch?nbein, 1986b). Closed form solutions are derived for several physiologically important cases, such as perfusion at steady state, transient and oscillatory flows. The results show that resting skeletal muscle has, over a wide range of perfusion pressures an almost linear pressure-flow curve. At low flow it exhibits nonlinearities. Vessel distensibility and the non-Newtonian properties of blood both have a strong influence on the shape of the pressure-flow curve. During oscillatory flow the muscle exhibits hysteresis. The theoretical results are in qualitative agreement with experimental observations.     

Diaphragmatic intramuscular pressure in relation to tension, shortening, and blood flow

We used an in situ isolated diaphragmatic preparation in anesthetized dogs to relate intramuscular pressure (IMP) to the blood flow, tension, and shortening of the diaphragm. In this preparation, the diaphragm shortens in a fashion similar to the intact diaphragm. Tension was measured by transducers attached to the left costal margin, which was detached from the rib cage and abdomen; IMP was measured by a miniature transducer placed between muscle fibers; length was measured by sonomicrometry; and diaphragmatic blood flow was monitored by measuring left phrenic arterial flow. In protocol 1, the relationships between tension, shortening, and IMP were assessed by stimulating the diaphragm for 2 s at various frequencies. Tension and shortening increased with increasing stimulation frequency up to 50 Hz with no change thereafter. Tension was linearly related to IMP. Similarly, there was a linear relationship between the degree of shortening and IMP; however, the slopes varied considerably between dogs. In protocol 2, the diaphragm was paced intermittently (12 trains/min, duty cycle of 0.5) with a gradual increase in stimulation frequency. Blood flow during contraction phase rose slightly at low tension and then declined significantly when tension exceeded 30% of maximum, whereas relaxation-phase flow increased with the increase in tension. IMP rose linearly with the increase in tension, and the IMP, at the point where contraction-phase flow became severely limited, was 50 +/- 14 mmHg (mean +/- SE). We conclude the following. 1) IMP is linearly related to tension and shortening; however, because tension and shortening changed simultaneously during contractions, the independent relationship of either tension or shortening and IMP remained untested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional blood flow to canine parietal pleura and internal intercostal muscle

Transcapillary Starling forces in the parietal pleura and the underlying interstitium may potentially contribute to the exchange of fluid across this barrier. However, the extent of blood flow to the parietal pleura has not been measured. Thus, using standard microsphere techniques, we compared blood flow to the parietal pleura, including the subpleural interstitium, with blood flow to the adjacent internal intercostal muscle, as well as with flows to other serous tissues, including mediastinal pleura, pericardium, and parietal peritoneum, in anesthetized dogs that were either breathing spontaneously (n = 9) or ventilated to control arterial PCO2 (n = 5). Blood flow (ml.min-1.g-1) was measured after 20 min of equilibration in four successive body positions: right lateral decubitus, supine, left lateral decubitus, and prone. Overall, flow to parietal pleura was not different in spontaneous [1.07 +/- 0.14 (SE)] and mechanically ventilated animals (0.74 +/- 0.11). Flow to the internal intercostal muscle was significantly less than pleural blood flow, averaging 0.24 +/- 0.03 and 0.16 +/- 0.03 in the same groups, although again there was no effect of ventilation mode. Blood flow to other serous tissues in the thoracic cavity, specifically the mediastinal pleura (0.67 +/- 0.14) and pericardium (0.88 +/- 0.22), was similar to parietal pleural flow, whereas that to the parietal peritoneum was an order of magnitude lower (0.09 +/- 0.02, P less than 0.05). Changing body position had no effect on blood flow to any of the sampled tissues. Blood flow to the dorsal aspect of the chest wall muscle in spontaneously breathing animals tended to be greater than that to lateral or ventral portions of the chest wall.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise-induced changes in cardiac gene expression and its relation to spatial maze performance

Cognitive performance is sensitive to both neural and non-neural changes induced by physical activity and inactivity. This study investigated whether access to physical activity outside a standard laboratory animal cage affected cognitive performance as measured by navigation of a spatial maze. It also examined gene expression in heart tissue for genes associated with cardiovascular function given recent reports of cognitive impairment associated with hyperlipidemia. Furthermore, we measured expression of neural-regulatory genes typically expressed in brain, but also found in cardiac tissue. Male Sprague-Dawley rats (n = 72) were separated into three groups having different access to physical activity: none outside a standard cage, twice-weekly physical activity, and every other day exercise on a running wheel. Compared with a sedentary group, spatial maze performance was enhanced in animals that had access to physical activity, either twice-weekly in a large box or every other day on a running wheel. Both the cardiovascular and neural-related genes expressed in the heart were distinguished by access to physical activity. Several genes that are associated with heart rate, cholesterol biosynthesis, blood pressure, and cell adhesion regulation, including GJA1, FDFT1, EDN1, and CD36, differed in animals based on access to physical activity. Neural-related genes expressed in cardiac tissue associated with neurite outgrowth, neuroplasticity, and neurogenesis including RTN4, HOMER2, ACTB, NCDN, KIF5B, and HMGB2, were expressed differently among the three groups. Significant shifts in ten cardiovascular and neural-related gene expressions in cardiac tissue were associated with physical activity and may have influenced learning and performance on a spatial maze.     

Exercise-induced abdominal muscle fatigue in healthy humans.

The abdominal muscles have been shown to fatigue in response to voluntary isocapnic hyperpnea using direct nerve stimulation techniques. We investigated whether the abdominal muscles fatigue in response to dynamic lower limb exercise using such techniques. Eleven male subjects [peak oxygen uptake (VO2 peak) = 50.0 +/- 1.9 (SE) ml.kg(-1).min(-1)] cycled at >90% VO2 peak to exhaustion (14.2 +/- 4.2 min). Abdominal muscle function was assessed before and up to 30 min after exercise by measuring the changes in gastric pressure (Pga) after the nerve roots supplying the abdominal muscles were magnetically stimulated at 1-25 Hz. Immediately after exercise there was a decrease in Pga at all stimulation frequencies (mean -25 +/- 4%; P < 0.001) that persisted up to 30 min postexercise (-12 +/- 4%; P = 0.001). These reductions were unlikely due to changes in membrane excitability because amplitude, duration, and area of the rectus abdominis M wave were unaffected. Declines in the Pga response to maximal voluntary expiratory efforts occurred after exercise (158 +/- 13 before vs. 145 +/- 10 cmH2O after exercise; P = 0.005). Voluntary activation, assessed using twitch interpolation, did not change (67 +/- 6 before vs. 64 +/- 2% after exercise; P = 0.20), and electromyographic activity of the rectus abdominis and external oblique increased during these volitional maneuvers. These data provide new evidence that the abdominal muscles fatigue after sustained, high-intensity exercise and that the fatigue is primarily due to peripheral mechanisms.     

Respiratory muscle blood flow in oleic acid-induced pulmonary edema

If respiratory muscle blood flow (RMBF) demands in pulmonary edema are large enough, an imbalance between supply and demand could lead to respiratory muscle failure. Therefore, to determine the magnitude of RMBF in this condition we produced pulmonary edema by injecting oleic acid into the pulmonary circulation and measured RMBF with radiolabeled microspheres injected into the left atrium. We then related changes in muscle blood flow to changes in respiratory variables including frequency of breathing (fb, breaths/min), tidal volume (VT, ml), ventilation (VE, ml . kg-1 . min-1), pleural pressure-time index (PTI, cmH2O), and dynamic compliance (Cdyn, 1/cmH2O) at 0 (control), 30, 60, and 120 min. Cardiac output and blood pressure did not change throughout the experiment, but hypoxia became progressively more severe with a final PO2 of 37 +/- 10 Torr. With pulmonary edema, fb rose from a control value of 32 +/- 13 to 111 +/- 33 at peak, VE rose from 237 +/- 90 to 806 +/- 188, but VT did not change. PTI rose from 54 +/- 16 to 180 +/- 48, and Cdyn decreased from 0.06 +/- 0.02 to 2.02 +/- 0.01. Diaphragmatic blood flow (Qdi) rose from 16.0 +/- 6.26 to 120.1 +/- 54.5 ml . min-1 X 100 g-1 and accounted for 55% of the total RMBF of 217 +/- 100 ml/min. The RMBF accounted for 11.4 +/- 4.7% of the cardiac output at peak affect. The rise in Qdi was best predicted by PTI and to a smaller extent by PO2.(ABSTRACT TRUNCATED AT 250 WORDS)