Cerebral blood flow during submaximal and maximal dynamic exercise in humans

Cerebral blood flow (CBF) in humans was measured at rest and during dynamic exercise on a cycle ergometer corresponding to 56% (range 27-85) of maximal O2 uptake (VO2max). Exercise bouts were performed by 16 male and female subjects, lasted 15 min each, and were carried out in a semisupine position. CBF (133Xe clearance) was expressed as the initial slope index (ISI) and as the first compartment flow (F1). CBF at rest [ISI, 58 (range 45-73); F1, 76 (range 55-98) ml.100 g-1.min-1] increased during exercise [ISI to 79 (57-94) and F1 to 118 (75-164) ml.100 g-1.min-1, P less than 0.01]. CBF did not differ significantly between work loads from 32 (24-33) to 86% (74-96) of VO2max (n = 10). During exercise, mean arterial pressure increased from 84 (60-100) to 101 (78-124) Torr (P less than 0.01) and PCO2 remained unchanged [5.1 (4.6-5.6) vs. 5.4 (4.4-6.3) kPa, n = 6]. These results demonstrate a median increase of 31% (0-87) in CBF by ISI and a median increase of 58% (0-133) in CBF by F1 during dynamic exercise in humans.     

Altered regional blood flow responses to submaximal exercise in older rats.

Maximal aerobic capacity and the ability to sustain submaximal exercise (Ex) declines with advancing age. Whether altered muscle blood flow (BF) plays a mechanistic role in these effects remains to be resolved. The present investigation determined the effects of aging on the hemodynamic and regional BF response to submaximal Ex in rats. Heart rate (HR), mean arterial pressure (MAP), and BF to different organs (kidneys, splanchnic organs, and 28 hindlimb muscles) were determined at rest and during submaximal treadmill Ex (20 m/min, 5% grade) with radiolabeled microspheres in young (Y; 6-8 mo old, 339 +/- 8 g, n = 9) and old (O; 27-29 mo old, 504 +/- 18 g, n = 7) Fischer 344 x Brown Norway rats. Results demonstrated that HR, MAP, and BF to the pancreas, small and large intestine, and total hindlimb musculature were similar between Y and O rats at rest. BF to the kidneys, spleen, and stomach were 33, 60, and 43% lower, respectively, in O compared with Y rats. BF to the total hindlimb musculature increased (P < 0.05) during Ex and was similar for both Y and O rats (Y: 16 +/- 3 to 124 +/- 7 vs. O: 20 +/- 3 to 137 +/- 12 ml.min-1.100 g-1). However, in O vs. Y rats, BF was reduced in 6 (highly oxidative) and elevated in 8 (highly glycolytic) of the 28 individual hindquarter muscles or muscle parts examined (P < 0.05). During Ex, BF to the spleen and stomach decreased (P < 0.05) from rest in Y rats, whereas BF decreased in the kidneys, pancreas, spleen, stomach, as well as the small and large intestines of O rats. In conclusion, these data demonstrate that, despite similar increases in total hindlimb BF in Y and O rats during submaximal Ex, there is a profound BF redistribution from highly oxidative to highly glycolytic muscles.     

Influence of respiratory muscle work on VO(2) and leg blood flow during submaximal exercise.

The work of breathing (W(b)) normally incurred during maximal exercise not only requires substantial cardiac output and O(2) consumption (VO(2)) but also causes vasoconstriction in locomotor muscles and compromises leg blood flow (Q(leg)). We wondered whether the W(b) normally incurred during submaximal exercise would also reduce Q(leg). Therefore, we investigated the effects of changing the W(b) on Q(leg) via thermodilution in 10 healthy trained male cyclists [maximal VO(2) (VO(2 max)) = 59 +/- 9 ml. kg(-1). min(-1)] during repeated bouts of cycle exercise at work rates corresponding to 50 and 75% of VO(2 max). Inspiratory muscle work was 1) reduced 40 +/- 6% via a proportional-assist ventilator, 2) not manipulated (control), or 3) increased 61 +/- 8% by addition of inspiratory resistive loads. Increasing the W(b) during submaximal exercise caused VO(2) to increase; decreasing the W(b) was associated with lower VO(2) (DeltaVO(2) = 0.12 and 0.21 l/min at 50 and 75% of VO(2 max), respectively, for approximately 100% change in W(b)). There were no significant changes in leg vascular resistance (LVR), norepinephrine spillover, arterial pressure, or Q(leg) when W(b) was reduced or increased. Why are LVR, norepinephrine spillover, and Q(leg) influenced by the W(b) at maximal but not submaximal exercise? We postulate that at submaximal work rates and ventilation rates the normal W(b) required makes insufficient demands for VO(2) and cardiac output to require any cardiovascular adjustment and is too small to activate sympathetic vasoconstrictor efferent output. Furthermore, even a 50-70% increase in W(b) during submaximal exercise, as might be encountered in conditions where ventilation rates and/or inspiratory flow resistive forces are higher than normal, also does not elicit changes in LVR or Q(leg).     

Sympathetic restraint of muscle blood flow at the onset of dynamic exercise.

Little attention has focused on sympathetic influences on skeletal muscle blood flow at the onset of exercise. We hypothesized that 1) the sympathetic nervous system constrains muscle blood flow and 2) the decline from peak blood flow is mediated by increasing sympathetic vasoconstrictor tone. Mongrel dogs (n = 7) ran on a treadmill after intra-arterial infusion of saline (control) or combined alpha(1)- and alpha(2)-adrenergic blockade (prazosin and rauwolscine). Immediate and rapid increases in hindlimb blood flow occurred at commencement of exercise with peak iliac blood flows averaging 933 +/- 79 and 1,227 +/- 90 ml/min during control and blockade conditions, respectively. At 1 min of exercise, hindlimb blood flow had decreased to 629 +/- 54 and 1,057 +/- 89 ml/min. In the absence of sympathetic vasoconstrictor tone, there was an enhanced peak blood flow at the onset of exercise. In addition, alpha-blockade attenuated the overshoot of hindlimb blood flow compared with the control condition. These data suggest that an immediate and sustained increase in sympathetic outflow restrains hindlimb blood flow at the onset of exercise and is responsible, at least in part, for an overshoot of blood flow to exercising skeletal muscle.     

Inspiratory muscle fatigue increases sympathetic vasomotor outflow and blood pressure during submaximal exercise

The purpose of this study was to elucidate the influence of inspiratory muscle fatigue on muscle sympathetic nerve activity (MSNA) and blood pressure (BP) response during submaximal exercise. We hypothesized that inspiratory muscle fatigue would elicit increases in sympathetic vasoconstrictor outflow and BP during dynamic leg exercise. The subjects carried out four submaximal exercise tests: two were maximal inspiratory pressure (PI(max)) tests and two were MSNA tests. In the PI(max) tests, the subjects performed two 10-min exercises at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and with or without inspiratory resistive breathing for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were each set at 0.5 s)]. Before and immediately after exercise, PI(max) was estimated. In MSNA tests, the subjects performed two 15-min exercises (spontaneous breathing for 5 min, with or without inspiratory resistive breathing for 5 min, and spontaneous breathing for 5 min). MSNA was recorded via microneurography of the right median nerve at the elbow. PI(max) decreased following exercise with resistive breathing, whereas no change was found without resistance. The time-dependent increase in MSNA burst frequency (BF) appeared during exercise with inspiratory resistive breathing, accompanied by an augmentation of diastolic BP (DBP) (with resistance: MSNA, BF +83.4%; DBP, +23.8%; without resistance: MSNA BF, +19.2%; DBP, -0.4%, from spontaneous breathing during exercise). These results suggest that inspiratory muscle fatigue induces increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise at mild intensity.     

Costal vs. crural diaphragmatic blood flow during submaximal and near-maximal exercise in ponies

The present study was carried out 1) to compare blood flow in the costal and crural regions of the equine diaphragm during quiet breathing at rest and during graded exercise and 2) to determine the fraction of cardiac output needed to perfuse the diaphragm during near-maximal exercise. By the use of radionuclide-labeled 15-micron-diam microspheres injected into the left atrium, diaphragmatic and intercostal muscle blood flow was studied in 10 healthy ponies at rest and during three levels of exercise (moderate: 12 mph, heavy: 15 mph, and near-maximal: 19-20 mph) performed on a treadmill. At rest, in eucapnic ponies, costal (13 +/- 3 ml.min-1.100 g-1) and crural (13 +/- 2 ml.min-1.100 g-1) phrenic blood flows were similar, but the costal diaphragm received a much larger percentage of cardiac output (0.51 +/- 0.12% vs. 0.15 +/- 0.03% for crural diaphragm). Intercostal muscle perfusion at rest was significantly less than in either phrenic region. Graded exercise resulted in significant progressive increments in perfusion to these tissues. Although during exercise, crural diaphragmatic blood flow was not different from intercostal muscle blood flow, these values remained significantly less (P less than 0.01) than in the costal diaphragm. At moderate, heavy, and near-maximal exercise, costal diaphragmatic blood flow (123 +/- 12, 190 +/- 12, and 245 +/- 18 ml.min-1.100 g-1) was 143%, 162%, and 162%, respectively, of that for the crural diaphragm (86 +/- 10, 117 +/- 8, and 151 +/- 14 ml.min-1.100 g-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neural control of muscle blood flow during exercise.

Activation of skeletal muscle fibers by somatic nerves results in vasodilation and functional hyperemia. Sympathetic nerve activity is integral to vasoconstriction and the maintenance of arterial blood pressure. Thus the interaction between somatic and sympathetic neuroeffector pathways underlies blood flow control to skeletal muscle during exercise. Muscle blood flow increases in proportion to the intensity of activity despite concomitant increases in sympathetic neural discharge to the active muscles, indicating a reduced responsiveness to sympathetic activation. However, increased sympathetic nerve activity can restrict blood flow to active muscles to maintain arterial blood pressure. In this brief review, we highlight recent advances in our understanding of the neural control of the circulation in exercising muscle by focusing on two main topics: 1) the role of motor unit recruitment and muscle fiber activation in generating vasodilator signals and 2) the nature of interaction between sympathetic vasoconstriction and functional vasodilation that occurs throughout the resistance network. Understanding how these control systems interact to govern muscle blood flow during exercise leads to a clear set of specific aims for future research.     

Sympathetic neural discharge and vascular resistance during exercise in humans

The purpose of this study was to determine the relationship between changes in efferent muscle sympathetic nerve activity (MSNA) to the lower leg and calf vascular resistance (CVR) during isometric exercise in humans. We made intraneural (microneurographic) determinations of MSNA in the right leg (peroneal nerve) while simultaneously measuring calf blood flow to the left leg, arterial pressure, and heart rate in 10 subjects before (control), during, and after (recovery) isometric handgrip exercise performed for 2.5 min at 15, 25, and 35% of maximal voluntary contraction (MVC). Heart rate and arterial pressure increased above control within the initial 30 s of handgrip at all levels, and the magnitudes of the increases at end contraction were proportional to the intensity of the exercise. In general, neither MSNA nor CVR increased significantly above control levels during handgrip at 15% MVC. Similarly, neither variable increased above control during the initial 30 s of handgrip at 25 and 35% MVC; however, during the remainder of the contraction period, progressive, parallel increases were observed in MSNA and CVR (P less than 0.05). The correlation coefficients relating changes in MSNA to changes in CVR for the individual subjects averaged 0.63 +/- 0.07 (SE) (range 0.30-0.91) and 0.94 +/- 0.06 (range 0.80-0.99) for the 25 and 35% MVC levels, respectively. During recovery, both MSNA and CVR returned rapidly toward control levels. These findings demonstrate that muscle sympathetic nerve discharge and vascular resistance in the lower leg are tightly coupled during and after isometric arm exercise in humans. Furthermore, the exercise-induced adjustments in the two variables are both contraction intensity and time dependent.     

Plateau in muscle blood flow during prolonged exercise in miniature swine

Cardiovascular, metabolic, and thermoregulatory responses were studied in eight male miniature swine during a prolonged treadmill run. Each animal underwent 8-10 wk of exercise training, thoracic surgery, and 3 wk of retraining before the experimental run. This regimen enabled the animals to run at 65% of the heart rate range (210-220 beats/min) for approximately 100 min. Skin wetting and a fan were used to cool the pigs during the run. Regional blood flow was significantly altered with the onset of exercise; however, hindlimb muscle and total gastrointestinal blood flow were unchanged throughout the exercise period. Compared with 5-min values, heart rate and cardiac output were significantly elevated by 17 beats/min and 31 ml.min-1.kg-1 at 60 min and by 20 beats/min and 33 ml.min-1.kg-1 at end exercise, respectively. Core temperatures increased between 5 and 30 min of exercise (39.4 vs. 39.9 degrees C) but then remained unchanged to the end of exercise. Mean arterial pressure, O2 consumption, and blood lactate did not change during the exercise bout. These data indicate that limiting increases in core temperature during prolonged exercise was associated with a plateau in active muscle blood flow.     

Progressive elevations in muscle blood flow during prolonged exercise in swine

Distribution of muscle blood flow has not been measured in man during prolonged exercise, but progressive elevations in skin flow coupled with constant cardiac output (QT) have suggested muscle blood flow may be compromised. However, previous experiments with rats demonstrated progressive increases in muscle blood flow over time during prolonged submaximal exercise. The present study was performed to study muscle blood flow in miniature swine during long-term exercise to shed light on this apparent anomaly. QT and distribution of QT were studied with radiolabeled microspheres while pigs ran on a level treadmill at a speed (10.5 km/h) requiring 71 +/- 4% of maximal O2 consumption (VO2 max). QT increased 23% from the 5th to the 30th min of exercise, whereas total skeletal muscle flow increased by 49%. Increases in flow in the muscles resulted from decreased resistance, since mean arterial pressure declined over this time period (-7%). In addition, the proportional increases in muscle flow were similar within synergistic muscle groups independent of fiber type composition (e.g., elbow extensors: 59-78%; elbow flexors: 26-40%). The factor that limited continued exercise appeared to be body temperature. Colonic temperature rose in linear fashion over time; the animals became exhausted at approximately 42 degrees C. These flow data are similar to previous findings in rats and indicate that during prolonged treadmill locomotion in quadrupedal animals muscle blood flow increases over time to near maximal levels.     

Muscle blood flow patterns during exercise in partially curarized rats

We studied the distribution of blood flow within and among muscles of partially curarized (40-100 micrograms/kg body wt) rats during preexercise and at 1 min of low-speed treadmill exercise (15 m/min). Glycogen loss in the deep red muscles and parts of muscles was significantly reduced in the curarized animals during exercise, indicating the fibers in these muscles were recruited to a lesser extent and/or had lower metabolisms than fibers in the same muscles of control rats. However, elevations in blood flow in the red muscles of the curarized rats were as great or greater than those in the control rats. Thus reduced recruitment and/or metabolism of the deep red muscle fibers of the curarized animals was not accompanied by reduced blood flow. These findings suggest a dissociation between red fiber metabolism and blood flow in the curarized rats during the 1st min of slow treadmill exercise and indicate that release of vasodilator substances or local physical factors associated with muscle fiber activity are not solely responsible for the initial hyperemia during exercise.     

Respiratory muscle work compromises leg blood flow during maximal exercise

Harms, Craig A., Mark A. Babcock, Steven R. McClaran, DavidF. Pegelow, Glenn A. Nickele, William B. Nelson, and Jerome A. Dempsey.Respiratory muscle work compromises leg blood flow during maximalexercise. J. Appl. Physiol.82(5): 1573-1583, 1997.We hypothesized that duringexercise at maximal O₂ consumption (O_{2 max}),high demand for respiratory muscle blood flow() would elicit locomotor muscle vasoconstrictionand compromise limb . Seven male cyclists(O_{2 max} 64 ± 6 ml · kg¹ · min¹)each completed 14 exercise bouts of 2.5-min duration atO_{2 max} on a cycleergometer during two testing sessions. Inspiratory muscle work waseither 1) reduced via aproportional-assist ventilator, 2)increased via graded resistive loads, or3) was not manipulated (control).Arterial (brachial) and venous (femoral) blood samples, arterial bloodpressure, leg (legs;thermodilution), esophageal pressure, andO₂ consumption(O₂) weremeasured. Within each subject and across all subjects, at constantmaximal work rate, significant correlations existed(r = 0.74-0.90;P < 0.05) between work of breathing(Wb) and legs (inverse), leg vascular resistance (LVR), and leg O₂(O_{2 legs};inverse), and between LVR and norepinephrine spillover. Mean arterialpressure did not change with changes in Wb nor did tidal volume orminute ventilation. For a ±50% change from control in Wb,legs changed 2 l/min or 11% of control, LVRchanged 13% of control, and O₂extraction did not change; thusO_{2 legs}changed 0.4 l/min or 10% of control. TotalO_{2 max} was unchangedwith loading but fell 9.3% with unloading; thusO_{2 legs}as a percentage of totalO_{2 max} was 81% incontrol, increased to 89% with respiratory muscle unloading, anddecreased to 71% with respiratory muscle loading. We conclude that Wbnormally incurred during maximal exercise causes vasoconstriction inlocomotor muscles and compromises locomotor muscle perfusion andO₂.

     

Forearm blood flow follows work rate during submaximal dynamic forearm exercise independent of sex.

To test the hypothesis that sex influences forearm blood flow (FBF) during exercise, 15 women and 16 men of similar age [women 24.3 +/- 4.0 (SD) vs. men 24.9 +/- 4.5 yr] but different forearm muscle strength (women 290.7 +/- 44.4 vs. men 509.6 +/- 97.8 N; P < 0.05) performed dynamic handgrip exercise as the same absolute workload was increased in a ramp function (0.25 W/min). Task failure was defined as the inability to maintain contraction rate. Blood pressure and FBF were measured on separate arms during exercise by auscultation and Doppler ultrasound, respectively. Muscle strength was positively correlated with endurance time (r = 0.72, P < 0.01) such that women had a shorter time to task failure than men (450.5 +/- 113.0 vs. 831.3 +/- 272.9 s; P < 0.05). However, the percentage of maximal handgrip strength achieved at task failure was similar between sexes (14% maximum voluntary contraction). FBF was similar between women and men throughout exercise and at task failure (women 13.6 +/- 5.3 vs. men 14.5 +/- 4.9 ml.min(-1).100 ml(-1)). Mean arterial pressure was lower in women at rest and during exercise; thus calculated forearm vascular conductance (FVC) was higher in women during exercise but similar between sexes at task failure (women 0.13 +/- 0.05 vs. men 0.11 +/- 0.04 ml.min(-1).100 ml(-1).mmHg(-1)). In conclusion, the similar FBF during exercise was achieved by a higher FVC in the presence of a lower MAP in women than men. Still, FBF remained coupled to work rate (and presumably metabolic demand) during exercise irrespective of sex.     

Effects of feeding on muscle blood flow during prolonged exercise in miniature swine

Eight exercise-trained miniature swine were studied during prolonged treadmill runs (100 min) under fasting and preexercise feeding conditions. Each animal ran at identical external work loads that corresponded to 65% of the heart rate reserve (210-220 beats/min) for the two exercise bouts. Cardiac outputs and stroke volumes were higher and heart rates lower for fed than for fasting runs (P less than 0.05). Preexercise feeding did not alter oxygen consumption, core temperature, mean arterial pressure, and arterial-mixed venous oxygen difference during prolonged exercise; however, mixed venous lactate concentration was lower at end exercise than during fasting conditions (1.2 vs. 2.6 mM, P less than 0.05). Microsphere measurements of regional blood flow revealed significantly higher total gastrointestinal flow (23%) for fed than for fasting conditions. Throughout the exercise bout, blood flow to the biceps femoris, semitendinosus, and tibialis anterior muscles was lower in fed than in fasted animals (P less than 0.05). Combined hindlimb muscle blood flow averaged 15 ml.min-1.100 g-1 (18%, P less than 0.05) lower under feeding than fasting run conditions. These findings provide further evidence that cardiovascular reflexes originate in the gut after feeding to increase cardiac output and redistribute a portion of the blood flow away from active muscle to the gastrointestinal tract during prolonged exercise.     

Regional muscle blood flow capacity and exercise hyperemia in high-intensity trained rats

The purpose of this study was to determine the effects of high-intensity treadmill exercise training on 1) the regional distribution of muscle blood flow within and among muscles in rats during high-intensity treadmill exercise (phase I) and 2) on the total and regional hindlimb skeletal muscle blood flow capacities as measured in isolated perfused rat hindquarters during maximal papaverine vasodilation (phase II). Two groups of male Sprague-Dawley rats were trained 5 days/wk for 6 wk with a program consisting of 6 bouts/day of 2.5-min runs at 60 m/min up a 15% grade with 4.5-min rest periods between bouts. After training, blood flows were measured with the radiolabeled microsphere technique (phase I) in pair-weighted sedentary control and exercise-trained rats while they ran at 60 m/min (0% grade). In phase II of the study, regional vascular flow capacities were determined at three perfusion pressures (30, 40, and 50 mmHg) in isolated perfused hindquarters of control and trained rats maximally vasodilated with papaverine. The results indicate that this exercise training program produces increases in the vascular flow capacity of fast-twitch glycolytic muscle tissue of rats. However, these changes were not apparent in the magnitude or distribution of muscle blood flow in conscious rats running at 60 m/min, since blood flows within and among muscles during exercise were the same in trained and control rats.     

Recruitment of single muscle fibers during submaximal cycling exercise.

In literature, an inconsistency exists in the submaximal exercise intensity at which type II fibers are activated. In the present study, the recruitment of type I and II fibers was investigated from the very beginning and throughout a 45-min cycle exercise at 75% of the maximal oxygen uptake, which corresponded to 38% of the maximal dynamic muscle force. Biopsies of the vastus lateralis muscle were taken from six subjects at rest and during the exercise, two at each time point. From the first biopsy single fibers were isolated and characterized as type I and II, and phosphocreatine-to-creatine (PCr/Cr) ratios and periodic acid-Schiff (PAS) stain intensities were measured. Cross sections were cut from the second biopsy, individual fibers were characterized as type I and II, and PAS stain intensities were measured. A decline in PCr/Cr ratio and in PAS stain intensity was used as indication of fiber recruitment. Within 1 min of exercise both type I and, although to a lesser extent, type II fibers were recruited. Furthermore, the PCr/Cr ratio revealed that the same proportion of fibers was recruited during the whole 45 min of exercise, indicating a rather constant recruitment. The PAS staining, however, proved inadequate to fully demonstrate fiber recruitment even after 45 min of exercise. We conclude that during cycling exercise a greater proportion of type II fibers is recruited than previously reported for isometric contractions, probably because of the dynamic character of the exercise. Furthermore, the PCr/Cr ratio method is more sensitive in determining fiber activation than the PAS stain intensity method.