Training increases muscle blood flow in rats with peripheral arterial insufficiency

This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running. Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF. Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk). Hindlimb BF was determined with 85Sr- and 141Ce-labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability). Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group. Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb. Two factors contributed to a higher BF to the distal limb muscle of the trained animals. A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue. In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025). The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals.

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Muscle blood flow in trained rats with peripheral arterial insufficiency

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.258.3.h759 ◽

1990 ◽

Vol 258 (3) ◽

pp. H759-H765 ◽

Cited By ~ 11

Author(s):

G. M. Mathien ◽

R. L. Terjung

Keyword(s):

Blood Flow ◽

Muscle Blood Flow ◽

Treadmill Running ◽

Partial Recovery ◽

Limb Blood Flow ◽

Distal Limb ◽

Exercise Hyperemia ◽

Intensity Of Exercise ◽

Peripheral Arterial ◽

O2 Delivery

The influence of exercise training on the recovery of muscle blood flow was assessed in rats with bilateral stenosis of the femoral artery, sufficient to limit exercise hyperemia in the distal hindlimb but not alter resting blood flow. Muscle blood flow was measured with 141Ce-labeled microspheres (15 microns) during treadmill running at 20 m/min in normal (n = 10), acute stenosed (n = 9), sedentary stenosed (n = 10) and trained stenosed (n = 13) animals. Treadmill training by a progressively intense program (up to 1 h/day, 7 days/wk for 6 wk) improved exercise tolerance evident both in duration and intensity of exercise. Total hindlimb blood flow (ml.min-1.100 g-1) was not different (P greater than 0.05) between all stenosed groups but was only 46-63% that of the normal group (P less than 0.05). Acute stenosis reduced distal blood flow to only 22% of that in the proximal hindlimb tissue. A significant (P less than 0.05) but limited recovery of distal limb blood flow (to 44% of proximal) occurred in sedentary stenosed rats after 6 wk of cage activity. Training further increased (P less than 0.05) distal limb blood flow to 69% of proximal. This partial recovery of distal limb blood flow could reflect a greater collateral vessel function or an enhanced vascularity of the distal limb tissue. Our results illustrate that peripheral adaptations occur within the ischemic hindlimb of trained animals to redistribute the limited O2 delivery to the active muscles most affected by stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Influence of Pentoxifylline and Torbafylline on Muscle Blood Flow in Animals With Peripheral Arterial Insufficiency

The Journal of Clinical Pharmacology ◽

10.1002/j.1552-4604.1990.tb03630.x ◽

1990 ◽

Vol 30 (8) ◽

pp. 704-710 ◽

Cited By ~ 7

Author(s):

Richard F. Dinn ◽

H. T. Yang ◽

Ronald L. Terjung

Keyword(s):

Blood Flow ◽

Muscle Blood Flow ◽

Arterial Insufficiency ◽

Peripheral Arterial

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Low-intensity training produces muscle adaptations in rats with femoral artery stenosis

Journal of Applied Physiology ◽

10.1152/jappl.1991.71.5.1822 ◽

1991 ◽

Vol 71 (5) ◽

pp. 1822-1829 ◽

Cited By ~ 26

Author(s):

H. T. Yang ◽

R. W. Ogilvie ◽

R. L. Terjung

Keyword(s):

Blood Flow ◽

Femoral Artery ◽

Muscle Blood Flow ◽

Exercise Program ◽

Artery Stenosis ◽

Peak Oxygen Consumption ◽

Adult Rats ◽

Grade 5 ◽

Peripheral Arterial

The effectiveness of a mild-intensity exercise program to induce adaptations within skeletal muscle of animals with peripheral arterial insufficiency was evaluated using an isolated perfused hindlimb preparation at a muscle blood flow similar to the peak found in vivo. Adult rats were subjected to bilateral femoral artery stenosis sufficient to limit peak blood flow during exercise but not alter resting blood flow. Stenosed-trained (Sten-Trained) rats walked on a treadmill at an easily achieved speed (20 m/min with a 15% grade) 5 days wk. Exercise tolerance improved from 10 min initially to 2 h/day. Non-stenosed-sedentary (Non-Sten-Sed) and stenosed-sedentary (Sten-Sed) animals were limited to cage activity. Oxygen delivery to the contracting muscles was similar among groups (7.0 +/- 0.4, 7.3 +/- 0.6, and 6.6 +/- 0.6 mumol.min-1.g-1 in Non-Sten-Sed, Sten-Sed, and Sten-Trained, respectively; n = 13 each). Force development was better maintained by Sten-Trained muscle (P less than 0.001) during a sequence of tetanic contraction conditions. Peak oxygen consumption was greater (P less than 0.05) in the Sten-Trained (5.23 +/- 0.34 mumol.min-1.g-1) than in Non-Sten-Sed (4.08 +/- 0.35) and Sten-Sed (4.34 +/- 0.37) rats. The increased peak oxygen extraction (P less than 0.05) by the muscle of the Sten-Trained rats (82.5 +/- 7.1% of oxygen inflow vs. 58.7 +/- 4.7 and 57.4 +/- 5.0%, respectively) was probably related to the increased muscle capillarity and mitochondrial enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Efficacy and specificity of bFGF increased collateral flow in experimental peripheral arterial insufficiency

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.278.6.h1966 ◽

2000 ◽

Vol 278 (6) ◽

pp. H1966-H1973 ◽

Cited By ~ 44

Author(s):

H. T. Yang ◽

Y. Feng ◽

Laura A. Allen ◽

Andrew Protter ◽

Ronald L. Terjung

Keyword(s):

Blood Flow ◽

Vascular Occlusion ◽

Treadmill Running ◽

Collateral Flow ◽

Collateral Blood Flow ◽

Angiogenic Growth Factors ◽

Short Term ◽

Arterial Insufficiency ◽

Peripheral Arterial ◽

Calf Muscles

Angiogenic growth factors could prove to be useful in managing peripheral arterial insufficiency. The present study was designed to evaluate the dose response of basic fibroblast growth factor (bFGF), the efficacy of critical routes and dosing regimens, and the specificity of action in rats with peripheral arterial insufficiency. Bilateral ligation of femoral arteries greatly reduces blood flow capacity to the calf muscles but does not impair resting flow needs. Collateral blood flow to calf muscles was determined 16 days postocclusion, during treadmill running, with 85Sr and 141Ce microspheres, in blinded-randomized trials that included intra-arterial and intravenous infusions and subcutaneous injections of recombinant human bFGF. Peak blood flow of 75–80 ml ⋅ min− 1 ⋅ 100 g− 1 for calf muscle was observed at a bFGF dose of 5 μg ⋅ kg− 1 ⋅ day− 1(ia for 14 days) compared with 50 ml ⋅ min− 1 ⋅ 100 g− 1 for vehicle groups. Similar increases in collateral blood flow were observed with short-term or prolonged and continuous or intermittent delivery of bFGF by any route. Collateral blood flows were similar in corresponding muscles across both limbs. Vascular remodeling induced by bFGF required attendant vascular occlusion, inasmuch as vessels in the normal nonoccluded vascular tree were unresponsive to circulating bFGF. Improvement in collateral blood flow with exogenous bFGF is robust, amenable to short-term administration, and requires vascular occlusion to be effective.

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Angiotensin-Converting Enzyme Inhibition Increases Exercise Tolerance and Muscle Blood Flow in Rats with Peripheral Arterial Insufficiency

The Journal of Clinical Pharmacology ◽

10.1002/j.1552-4604.1994.tb02003.x ◽

1994 ◽

Vol 34 (4) ◽

pp. 345-355 ◽

Cited By ~ 6

Author(s):

H. T. Yang ◽

Ronald L. Terjung

Keyword(s):

Blood Flow ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibition ◽

Exercise Tolerance ◽

Muscle Blood Flow ◽

Angiotensin Converting Enzyme Inhibition ◽

Converting Enzyme ◽

Converting Enzyme Inhibition ◽

Arterial Insufficiency ◽

Peripheral Arterial

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Intermittent pneumatic leg compressions enhance muscle performance and blood flow in a model of peripheral arterial insufficiency

Journal of Applied Physiology ◽

10.1152/japplphysiol.01337.2011 ◽

2012 ◽

Vol 112 (9) ◽

pp. 1556-1563 ◽

Cited By ~ 7

Author(s):

Bruno T. Roseguini ◽

Arturo A. Arce-Esquivel ◽

Sean C. Newcomer ◽

Hsiao T. Yang ◽

Ronald Terjung ◽

...

Keyword(s):

Blood Flow ◽

Exercise Tolerance ◽

Citrate Synthase ◽

Arterial Disease ◽

Muscle Performance ◽

Sprague Dawley ◽

Arterial Insufficiency ◽

Mechanistic Basis ◽

Peripheral Arterial

Despite the escalating prevalence in the aging population, few therapeutic options exist to treat patients with peripheral arterial disease. Application of intermittent pneumatic leg compressions (IPC) is regarded as a promising noninvasive approach to treat this condition, but the clinical efficacy, as well the mechanistic basis of action of this therapy, remain poorly defined. We tested the hypothesis that 2 wk of daily application of IPC enhances exercise tolerance by improving blood flow and promoting angiogenesis in skeletal muscle in a model of peripheral arterial insufficiency. Male Sprague-Dawley rats were subjected to bilateral ligation of the femoral artery and randomly allocated to treatment or sham groups. Animals were anesthetized daily and exposed to 1-h sessions of bilateral IPC or sham treatment for 14–16 consecutive days. A third group of nonligated rats was also studied. Marked increases in treadmill exercise tolerance (∼33%, P < 0.05) and improved muscle performance in situ (∼10%, P < 0.05) were observed in IPC-treated animals. Compared with sham-treated controls, blood flow measured with isotope-labeled microspheres during in situ contractions tended to be higher in IPC-treated animals in muscles composed of predominantly fast-twitch white fibers, such as the plantaris (∼93%, P = 0.02). Capillary contacts per fiber and citrate synthase activity were not significantly altered by IPC treatment. Collectively, these data indicate that IPC improves exercise tolerance in a model of peripheral arterial insufficiency in part by enhancing blood flow to collateral-dependent tissues.

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Muscle blood flow during exercise in sedentary and trained hypothyroid rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.269.6.h1949 ◽

1995 ◽

Vol 269 (6) ◽

pp. H1949-H1954 ◽

Cited By ~ 10

Author(s):

R. M. McAllister ◽

M. D. Delp ◽

K. A. Thayer ◽

M. H. Laughlin

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Citrate Synthase ◽

Vastus Lateralis ◽

Muscle Blood Flow ◽

Treadmill Running ◽

Exercise Intolerance ◽

Vastus Lateralis Muscle ◽

Blood Flows ◽

Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

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A method for using microspheres to measure muscle blood flow in exercising rats

Journal of Applied Physiology ◽

10.1152/jappl.1982.52.6.1629 ◽

1982 ◽

Vol 52 (6) ◽

pp. 1629-1635 ◽

Cited By ~ 53

Author(s):

M. H. Laughlin ◽

R. B. Armstrong ◽

J. White ◽

K. Rouk

Keyword(s):

Blood Flow ◽

High Speed ◽

Muscle Blood Flow ◽

Reference Sample ◽

Left Ventricular ◽

Ascending Aorta ◽

Treadmill Running ◽

Tissue Samples ◽

Skeletal Muscle Blood Flow ◽

Catheter Implantation

A catheter-implantation procedure allowing use of the radiolabeled microsphere (MS) technique for measuring skeletal muscle blood flow (BF) in rats during high-speed treadmill running was desired. Attempts to use existing procedures were unsuccessful. We found that Silastic catheters (0.02 in. ID X 0.037 in. OD) placed in the ascending aorta (for MS infusions) and the renal artery (for reference sample withdrawal) minimized these exercise performance problems. It was then necessary to establish that aortic MS infusions result in good MS-blood mixing. We tested the method with the following: 1) the radioactivities found in reference withdrawal samples taken from two locations in the aorta were compared after left ventricular (LV) infusion and after aortic infusion; 2) BFs to bilaterally paired tissues were compared in anesthetized and conscious rats with LV and aortic infusions; 3) the distribution of MSs in the muscles was studied histologically; and 4) BFs in bilaterally paired tissues were compared in rats with aortic MS infusions during treadmill running. The results indicate that 1) the percent difference between the radioactivities found in the proximal and distal reference withdraw samples was the same for LV and aortic MS infusions; 2) BF to bilaterally paired tissue samples was the same with both LV or aortic MS infusions; 3) the MSs were distributed uniformly within muscles, and MS aggregation was not a significant problem; and 4) BFs to bilaterally paired tissue samples were the same in exercising rats. We conclude that this technique can be used to measure muscle BF in rats running on a treadmill.

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Near infrared spectroscopy-guided exercise training for claudication in peripheral arterial disease

European Journal of Preventive Cardiology ◽

10.1177/2047487318795192 ◽

2018 ◽

Vol 26 (5) ◽

pp. 471-480 ◽

Cited By ~ 4

Author(s):

Jonathan R Murrow ◽

Jared T Brizendine ◽

Bill Djire ◽

Hui-Ju Young ◽

Stephen Rathbun ◽

...

Keyword(s):

Blood Flow ◽

Infrared Spectroscopy ◽

Near Infrared Spectroscopy ◽

Near Infrared ◽

Muscle Blood Flow ◽

Arterial Disease ◽

Walking Program ◽

Peripheral Arterial ◽

Walking Time ◽

Mitochondrial Capacity

Rationale Supervised treadmill exercise for claudication in peripheral arterial disease is effective but poorly tolerated because of ischemic leg pain. Near infrared spectroscopy allows non-invasive detection of muscle ischemia during exercise, allowing for characterization of tissue perfusion and oxygen utilization during training. Objective We evaluated walking time, muscle blood flow, and muscle mitochondrial capacity in patients with peripheral artery disease after a traditional pain-based walking program and after a muscle oxygen-guided walking program. Method and results Patients with peripheral artery disease trained thrice weekly in 40-minute-long sessions for 12 weeks, randomized to oxygen-guided training ( n = 8, age 72 ± 9.7 years, 25% female) versus traditional pain-based training ( n = 10, age 71.6 ± 8.8 years, 20% female). Oxygen-guided training intensity was determined by maintaining a 15% reduction in skeletal muscle oxygenation by near infrared spectroscopy rather than relying on symptoms of pain to determine exercise effort. Pain free and maximal walking times were measured with a 12-minute Gardner treadmill test. Gastrocnemius mitochondrial capacity and blood flow were measured using near infrared spectroscopy. Baseline pain-free walking time was similar on a Gardner treadmill test (2.5 ± 0.9 vs. 3.6 ± 1.0 min, p = 0.5). After training, oxygen-guided cohorts improved similar to pain-guided cohorts (pain-free walking time 6.7 ± 0.9 vs. 6.9 ± 1.1 min, p < 0.01 for change from baseline and p = 0.97 between cohorts). Mitochondrial capacity improved in both groups but more so in the pain-guided cohort than in the oxygen-guided cohort (38.8 ± 8.3 vs. 14.0 ± 9.3, p = 0.018). Resting muscle blood flow did not improve significantly in either group with training. Conclusions Oxygen-guided exercise training improves claudication comparable to pain-based training regimens. Adaptations in mitochondrial function rather than increases in limb perfusion may account for functional improvement. Increases in mitochondrial oxidative capacity may be proportional to the degree of tissue hypoxia during exercise.

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