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Biomedical subjects

M H Laughlin

Publications and source records attributed to M H Laughlin.

At least 145 records · Page 8Linked to original sources

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.

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Muscle blood flow and fiber activity in partially curarized rats during exercise.

We previously reported that low doses of d-tubocurarine attenuated glycogen loss in red muscles of rats during treadmill walking but that the initial hyperemia in the muscles was normal. The present studies were performed to 1) determine with electromyography (EMG) whether red muscle fiber activity is reduced in walking, curarized rats and 2) study muscle blood flow and glycogen loss during running with different doses of curare (dose response). At 0.5 min of treadmill walking (15 m/min), integrated EMG in vastus intermedius (VI) muscle was reduced by an average of 18% in curarized (60 micrograms/kg) rats, although blood flow (measured with microspheres) was the same as in saline control rats. Comparison of blood flows and glycogen loss in quadriceps muscles at 1 min of treadmill running (30 m/min) with different curare doses (20-60 micrograms/kg) demonstrated that red muscle glycogen loss was inversely related to curare dose but that blood flows in the same muscles were unaffected by curare. These findings provide support for our previous conclusion that at the initiation of low to moderate treadmill exercise, red muscle blood flow is not proportional to the activity or metabolism of the muscle fibers.

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Myocardial capillarity and maximal capillary diffusion capacity in exercise-trained dogs.

Our purpose was to determine whether changes in myocardial capillarity underlie the exercise training-induced increases in coronary transport capacity previously observed in dogs (J. Appl. Physiol. 58: 468-476, 1985). The approach was to measure capillary diffusion capacity (PS) in working hearts and then measure capillary numerical density (CD), capillary surface area density (CSA), and capillary volume density (CV) in specimens from perfused-fixed hearts. Eight dogs (20-30 kg) were exercise trained (ET) for 12-18 wk and compared with a group of seven control dogs. PS for 51Cr-labeled ethylenediaminetetraacetic acid was determined during maximal adenosine coronary vasodilation with perfusion pressures equal to 100 mmHg in both groups. The trained dogs' maximal PS averaged 58 +/- 10 ml.min-1.100 g-1, which was significantly greater than the control value (31 +/- 6). Maximal PS was linearly related to CV (r = 0.61) and CSA (r = 0.78) in the ET group. However, there was no difference between control and trained average left ventricular CD, CSA, CV, or intercapillary distance. The data indicate that although coronary blood flow capacity and capillary transport capacity may be improved in exercise-trained dog hearts, these changes are not the result of an increase in myocardial capillarity. Rather, the increased maximal PS appears to be due to changes in the determinants of capillary blood flow and/or the relationship between capillary area available for exchange and capillary perfusion.

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Atropine: no effect on exercise muscle hyperemia in conscious rats.

The purpose of this study was to test the hypothesis that muscarinic cholinergic receptors are involved in the initial vasodilation in red muscle vascular beds of conscious rats performing slow locomotory exercise. Atropine sulfate (1 mg/kg, ia) was administered to one group of rats in which distribution of cardiac output was estimated with radiolabeled microspheres immediately before exercise while the animals were standing on the treadmill and at 30 s and 5 min of treadmill walking at 15 m/min. Blood flows within and among muscles in the atropine-treated animals were compared with flows in control rats that were given a sham injection of an equal volume of physiological saline. Heart rates were elevated above those of control animals in the atropinized rats during preexercise (+17%) and at 30 s of exercise (+15%). However, distributions and magnitudes of blood flows in nonmuscular tissues and within and among skeletal muscles were the same (P greater than 0.05) in atropinized and control rats during preexercise and at both exercise times, indicating that atropine had no effect on the distribution of cardiac output in the rats. It is concluded that muscarinic cholinergic receptors do not play a significant role in elevating muscle blood flow in conscious rats, either during the preexercise anticipatory phase or during slow locomotory exercise.

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Blood flow and glycogen use in hypertrophied rat muscles during exercise.

Previous findings suggest that skeletal muscle that has enlarged as a result of removal of synergistic muscles has a similar metabolic capacity and improved resistance to fatigue compared with normal muscle. The purpose of the present study was to follow blood flow and glycogen loss patterns in hypertrophied rat plantaris plantaris and soleus muscles during treadmill exercise to provide information on the adequacy of perfusion of the muscles during in vivo exercise. Thirty days following surgical removal of gastrocnemius muscle, blood flows (determined with radiolabeled microspheres) and glycogen concentrations were determined in all of the ankle extensor muscles of experimental and sham-operated control rats during preexercise and after 5-6 min of treadmill exercise at 15 m/min. There were no differences (P greater than 0.05) in blood flows per unit mass or glycogen concentrations between control and hypertrophied plantaris or soleus muscles at either time, although both muscles were larger (P less than 0.05) in the experimental group (plantaris: 95%; soleus: 40%). None of the other secondary ankle extensor muscles (tibialis posterior, flexor digitorum longus or flexor hallicus longus) hypertrophied in response to removal of gastrocnemius. These results provide indirect evidence that O2 delivery in the enlarged muscles is not compromised during low-intensity treadmill exercise due to limited perfusion.

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Transcapillary exchange in the hindlimb and intestine of dogs with right heart failure.

The effects of chronic right ventricular volume overload, congestive heart failure (HF) on transcapillary exchange of lipid-insoluble solutes in the hindlimb and small intestine were studied in anesthetized dogs. Using the single injection indicator diffusion method, extractions (E), capillary clearances (C), and capillary permeability surface area products (PS) of urea, sucrose, and inulin were measured in the hindlimb and small intestine of 16 control and 14 HF dogs. Right HF was caused by surgically produced tricuspid insufficiency. The HF dogs exhibited increased central venous pressures, right ventricular end diastolic pressure, and heart rates as well as gross ascites and pleural effusion. The small intestine of the HF dogs demonstrated increased E, C and PS values for all three solutes, while no changes were seen in the hindlimb. These changes in the capillary bed of the small intestine could be due to an increase in capillary permeability, and/or capillary surface area.

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The effects of +Gz on the coronary circulation: a review.

The exposure of the human body to +Gz acceleration produces dramatic effects on the cardiovascular system. For example, during +Gz stress, heart rate has been reported to increase in excess of 200 b . min-1 and left ventricular pressure has been estimated to reach 300 mm Hg. Several reviews have dealt with the overall effects of +Gz stress on the cardiovascular system. However, none of these reviews has dealt specifically with the effects of +Gz on the coronary circulation and on the ability of the coronary circulation to maintain adequate perfusion of the heart. A common misconception exists within the aeromedical community that coronary blood flow must be compromised during +Gz due to the high heart rates and stress levels encountered during +Gz exposures. The purpose of this review is to deal with this issue by reviewing available information about basic coronary physiology, acceleration physiology, and their interaction. The current state of our understanding of basic coronary function will first be summarized. Serious students of coronary physiology are referred to other reviews for more detailed discussion. The current understanding of normal coronary function will then be integrated with the available information about the effects of +Gz on the heart and coronary circulation. Finally, potential chronic effects of +Gz and its interrelationships with cardiac and cardiovascular pathology in relation to the coronary circulation will be briefly considered.

Acceleration↗

Effects of exercise training on coronary transport capacity.

Coronary transport capacity was estimated in eight sedentary control and eight exercise-trained anesthetized dogs by determining the differences between base line and the highest coronary blood flow and permeability-surface area product (PS) obtained during maximal adenosine vasodilation with coronary perfusion pressure constant. The anterior descending branch of the left coronary artery was cannulated and pump-perfused under constant-pressure conditions (approximately equal to 100 Torr) while aortic, central venous, and coronary perfusion pressures, heart rate, electrocardiogram, and coronary flow were monitored. Myocardial extraction and PS of 51Cr-labeled ethylenediaminetetraacetic acid were determined with the single-injection indicator-diffusion method. The efficacy of the 16 +/- 1 wk exercise training program was shown by significant increases in the succinate dehydrogenase activities of the gastrocnemius, gluteus medialis, and long head of triceps brachii muscles. There were no differences between control and trained dogs for either resting coronary blood flow or PS. During maximal vasodilation with adenosine, the trained dogs had significantly lower perfusion pressures with constant flow and, with constant-pressure vasodilation, greater coronary blood flow and PS. It is concluded that exercise training in dogs induces an increased coronary transport capacity that includes increases in coronary blood flow capacity (26% of control) and capillary diffusion capacity (82% of control).

Adenosine↗

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.

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Rat muscle blood flows during high-speed locomotion.

We previously studied blood flow distribution within and among rat muscles as a function of speed from walking (15 m/min) through galloping (75 m/min) on a motor-driven treadmill. The results showed that muscle blood flows continued to increase as a function of speed through 75 m/min. The purpose of the present study was to have rats run up to maximal treadmill speeds to determine if blood flows in the muscles reach a plateau as a function of running speed over the animals' normal range of locomotory speeds. Muscle blood flows were measured with radiolabeled microspheres at 1 min of running at 75, 90, and 105 m/min in male Sprague-Dawley rats. The data indicate that even at these relatively high treadmill speeds there was still no clear evidence of a plateau in blood flow in most of the hindlimb muscles. Flows in most muscles continued to increase as a function of speed. These observed patterns of blood flow vs. running speed may have resulted from the rigorous selection of rats that were capable of performing the high-intensity exercise and thus only be representative of a highly specific population of animals. On the other hand, the data could be interpreted to indicate that the cardiovascular potential during exercise is considerably higher in laboratory rats than has normally been assumed and that inadequate blood flow delivery to the muscles does not serve as a major limitation to their locomotory performance.

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Metabolic indicators of fibre recruitment in mammalian muscles during locomotion.

Fast-twitch-oxidative-glycolytic (FOG), fast-twitch-glycolytic (FG) and slow-twitch-oxidative (SO) fibres are distributed within and among physiological extensor muscles in mammals in predictable patterns. Deep muscles and the deep portions of extensor muscles are primarily composed of SO and FOG fibres, and the more peripheral portions of the muscles have higher concentrations of FG fibres. During terrestrial locomotion, the fibres are recruited in this same general order from postural standing through high speed running to jumping (i.e. during standing deep SO fibres are active and during locomotion there is a progressive peripheral recruitment of fibres from SO to FOG to FG). Several metabolic indicators may be used to map these fibre recruitment patterns, including glycogen loss in fibres, metabolic enzyme changes during training at different speeds, and distribution of blood flow within and among the muscles. Concerning the latter, during standing in rats blood flows in the hindlimb muscles are directly proportional to the SO fibre populations in the muscles. However, during locomotion the elevations in blood flow over pre-exercise are a function of the populations of FOG fibres in the muscles. Blood flows in the peripheral white portions (FG fibres) of extensor muscles are not significantly elevated until the rats run at high speeds, when the FG fibres presumably are recruited. During swimming, when flexor muscles are relatively more active than extensor muscles (as compared with terrestrial locomotion), blood flows in the flexors are correspondingly higher. Thus, there exists a clear 'biological economy' in the matching of blood flow to the specific fibres that are active within and among muscles during exercise.

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Muscle blood flow during locomotory exercise.

Mammalian skeletal muscles are composed of three primary muscle fiber types, FOG, FG, and SO. These fiber types are distributed within and among muscles in predictable patterns. Current data indicate that blood flows to inactive muscles composed of the various fiber types are approximately equal. Total muscle blood flow increases when the animal stands up. When maintaining posture (standing), the muscular force is provided by the SO fibers. These fibers receive the highest blood flows under these conditions. When the animal walks the SO fibers remain active and the additional muscular force is provided by FOG fibers. The increased muscle blood flow during exercise is primarily directed to the active FOG fibers. At fast running speeds, FG fibers are additionally recruited and blood flow increases in muscle areas composed of FG fibers. However, the FG blood flows per gram of tissue are much less than in the oxidative muscles. Thus, muscle blood flow is primarily directed to the active high oxidative muscle fibers within and among the muscles during normal activities. Much is known about factors believed to link blood flow to metabolism in skeletal muscle and about the reflex control of skeletal muscle vascular beds. However, the mechanisms responsible for blood flow control during locomotory exercise are yet to be established. It appears that the different muscle fiber types may have qualitatively similar blood flow control mechanisms with quantitative differences in relation to each fiber type. The capacity for blood flow in skeletal muscle is related to the oxidative potential of the muscles. Blood flows in high-oxidative muscles may reach 400-600 ml/min/100 g, which is considerably higher than the commonly accepted values for maximal muscle blood flow. Also, muscle blood flows are higher during locomotory exercise in conscious animals than in in situ electrical stimulation experiments. Chronic exercise training does not appear to change total muscle blood flow during locomotory exercise. However, the distribution of blood flow within and among muscles changes so that the deep red muscle fibers have higher flows during exercise. While data exist suggesting that blood flow capacity is increased with exercise training, this remains controversial.

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Exercise blood flow patterns within and among rat muscles after training.

This study was designed to determine the influence of a long-term, moderate-intensity treadmill training program on the distribution of blood flow within and among muscles of rats during exercise. One group (T) of male Sprague-Dawley rats trained for 1 h/day for 13-17 wk at 30 m/min on a motor-driven treadmill. A second group (UT) of rats was conditioned for 10 min/day for 4 wk at the same speed. Muscle succinate dehydrogenase activities were higher in T than UT rats indicating a significant training effect. Blood flows (BFs) in 32 hindlimb muscles or muscle parts and other selected organs were measured in the two groups with radiolabeled microspheres during preexercise and while the rats ran for 30 s, 5 min, or 15 min at 30 m/min on the treadmill. The data indicate 1) there were no differences in total hindlimb muscle BF between UT and T rats at any time; however, 2) T rats had higher preexercise heart rates and higher muscle BFs in the deep red extensor muscles, suggesting a greater anticipatory response to the impending exercise; 3) T rats demonstrated more rapid elevations in BF in the red extensor muscles at the commencement of exercise; 4) T rats had higher BFs in red extensor muscles during exercise, whereas UT rats had higher BFs in white muscles; and 5) T rats maintained higher BFs in the visceral organs during exercise. These findings demonstrate that exercise training results in changes in the distribution of BF within and among muscles and among organs during exercise. Specifically, data indicate the high-oxidative motor units that are primarily recruited in the muscles during the initial stages of moderate treadmill exercise receive higher blood flows in the trained rats; this presumably contributes to increased resistance to fatigue.

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Muscular blood flow distribution patterns in the hindlimb of swimming rats.

We previously observed that muscle blood flow (MBF) is primarily directed to the active oxidative muscle fibers within muscles of rats during treadmill exercise. Since muscle fiber recruitment patterns and the relative level of activities of muscles are distinctly different in swimming and treadmill exercise, we hypothesized that the distribution of MBF would also be different. The purpose of this study was to measure the distribution of MBF in swimming rats for comparison with the patterns previously observed in treadmill exercise. MBF was measured with labeled microspheres in 25 hindlimb muscles before, during, and after 5 min of swimming. During swimming, MBFs ranged from 10 to 403 ml X min-1 X 100 g-1 in the white vastus lateralis and red tibialis anterior, respectively. MBFs were increased during swimming in most muscles with the flexor muscles generally showing larger increases than the extensor muscles. Comparison of swimming with treadmill exercise indicates that swimming produces greater increases in MBFs in flexor muscles than in extensor muscles, whereas treadmill exercise produces larger increases in extensor muscles. The increased MBF during swimming was directed to the fast-twitch oxidative fibers. Therefore regional hindlimb MBF distribution is different in swimming than in treadmill exercise, and it appears that MBF is matched to the fiber recruitment patterns during both types of locomotory exercise.

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Coronary transport reserve in normal dogs.

This study was designed to determine an acceptable method for producing maximal coronary vasodilation for quantifying coronary blood flow reserve and coronary capillary transport reserve. The anterior descending branch of the left coronary artery was cannulated and pump-perfused while aortic, central venous, and coronary perfusion pressures, heart rate, electrocardiogram, blood gases, and coronary blood flow (CBF) were continuously monitored. All parameters were measured at four to six points along the coronary pressure-flow autoregulation curve. Myocardial extraction and permeability-surface area products (PS) of 51Cr-ethylenediaminetetraacetic acid were determined with the single-injection indicator-diffusion method in intact working hearts of anesthetized dogs. Maximal vasodilations were produced with 2-min coronary occlusions and with intracoronary infusions of adenosine (ADO), dipyridamole, ADO + dipyridamole, papaverine, and ADO + alpha 1-receptor blockade. ADO was chosen to quantify coronary transport reserve because it produced maximal CBF's and PS's that were reproducible within and among animals and produced minimal effects on the cardiovascular system. Under base-line conditions, there was no relationship between PS and perfusion pressure. Base-line PS averaged 20 +/- 2 ml X min-1 X 100 g-1. Maximal vasodilation with constant CBF had no significant effect on PS. During maximal vasodilation, CBF and PS increased linearly with increasing perfusion pressure, and PS increased linearly with increasing plasma flow. Constant pressure maximal vasodilation with ADO caused PS to increase to 36 +/- 4 ml X min-1 X 100 g-1, and CBF was increased 380%.

Adenosine↗

Blood flows within and among rat muscles as a function of time during high speed treadmill exercise.

The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution patterns within and among rat hind-limb skeletal muscles before, during, and after high speed treadmill running at 60 min-1 to fatigue. Exercise blood flows were measured at the 0.5, 1, 2 and 3 min time points. Pre-exercise blood flow was highest in physiological extensor muscles or muscle parts with large populations of slow-twitch muscle fibres, e.g. soleus (197 ml min-1 100 g-1). Blood flows were lowest to muscles or muscle parts with high proportions of fast-twitch glycolytic fibres, e.g. white gastrocnemius (15 ml min-1 100 g-1). The most rapid increases in blood flow at the beginning of exercise and the highest peak blood flows during exercise generally occurred in physiological extensor muscles with relatively high populations of fast-twitch oxidative fibres. For example, red gastrocnemius muscle blood flow increased by 271 ml min-1 100 g-1 during the first 30 s of exercise, and attained a peak flow of 395 ml min-1 100 g-1 by the third minute of exercise. On the other hand, the slowest elevations in blood flow at the start of exercise and the lowest peak flows were observed in muscles with high populations of fast-twitch glycolytic fibres. White gastrocnemius muscle, for example, increased its blood flow by 16 ml min-1 100 g-1 during the first 30 s of running, and had a peak flow of 76 ml min-1 100 g-1 by the end of 3 min exercise. These relationships between blood flows and fibre type populations were less consistent in physiological flexor muscle groups. Following exercise, blood flows in high-oxidative muscles returned to the pre-exercise levels within 30 s. However, in low-oxidative muscles, return of blood flows to the pre-exercise levels were slower. Thus, marked differences in the absolute magnitudes of blood flows and in the rates of change in blood flows were observed within and among the hind-limb muscles before, during and after exercise. These differences were related to the fibre type compositions of the muscles.

Animals↗

Rat muscle blood flows as a function of time during prolonged slow treadmill exercise.

The purpose of these experiments was to follow blood flows (BF) within and among rat hindlimb skeletal muscles as a function of time during prolonged low-speed treadmill locomotion. Male Sprague-Dawley rats were chronically instrumented with two Silastic catheters, one in the ascending aorta via the right carotid artery for microsphere infusion and one in the left renal artery for arterial reference blood sample withdrawal. BFs were measured, using the radio-labeled microsphere technique, within and among 23 major skeletal muscles of rats before exercise and during treadmill locomotion at 15 m/min at 0.5, 1, 5, 15, 30, 54, and 71 min of exercise. During preexercise, BF was highest to deeply situated slow-twitch muscles (210 ml . min-1 . 100 g-1 in vastus intermedius) in the antigravity extensor muscle groups. During the 1st min of exercise each of the hindlimb muscles displayed one of four general BF patterns. 1) Many muscles had an "overshoot" in BF during the first 30 s of exercise; 2) some muscles attained steady-state exercise levels in the first 30 s of exercise; 3) others showed a decrease below preexercise levels; and 4) some muscles showed no change from preexercise. Most muscles showed a gradual increase in BF from 5 min through 54 min of exercise. The elevations in BF over preexercise were primarily directed to fast-twitch oxidative muscle fibers in the antigravity extensor muscles, and BFs to extensor muscle groups were generally higher than those to flexor muscle groups. The data demonstrate that BFs within and among rat muscles are heterogeneous, both before exercise and during prolonged low-intensity treadmill walking to fatigue. Mechanisms regulating the distribution of flow to the muscles remain to be elucidated.

Adipose Tissue↗

Metabolism of rats running up and down an incline.

The purpose of these experiments was to determine oxygen consumption (VO2) in rats as a function of treadmill speed (10, 20, 30, 40, and 50 m . min-1) as they ran on the level and up and down a 16 degree (17.8%) incline. The slopes of the regression lines relating VO2 (ml O2 . kg-1 . min-1) to running speed (m . min-1) were linear for all three inclines. The regression slope for uphill runners (y = 1.25x + 47.7) was greater than the regression slopes for level (y = 0.88x + 41.2) (P less than 0.025) or downhill (y = 0.68x + 39.7) (P less than 0.005) runners, and the regression slope for level runners was greater than that for downhill runners (P less than 0.10). All VO2 measurements were submaximal. In conclusion, incline has a significant effect on the metabolism of rats running on a motor-driven treadmill.

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