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Biomedical subjects

R B Armstrong

Publications and source records attributed to R B Armstrong.

At least 73 records · Page 4Linked to original sources

Isotretinoin revisited.

Isotretinoin (13-cis-retinoic acid) remains the drug of choice for treatment of severe, recalcitrant nodulocystic acne that is unresponsive to conventional therapy, including oral antibiotics. The drug has been shown to produce dramatic clearing of lesions and prolonged remissions. The length of remission may be dependent on both the dosage used and the duration of therapy. Since fetal malformations have been observed in infants born of mothers taking isotretinoin during pregnancy, it is mandatory to prevent women who are pregnant or may become pregnant during treatment from taking isotretinoin. Because the half-life of isotretinoin is ten to twenty hours, and because it is eliminated from the body rapidly enough, women may become pregnant one month after discontinuation of therapy without an increased risk of birth defects. Common side effects of the drug include mucocutaneous reactions, serum lipid alterations, eye irritation, and myalgias. Less commonly observed are hyperostoses and exuberant granulation tissue, and rarely, pseudotumor cerebri. Recommendations for substantially reducing or eliminating these effects are made.

Abnormalities, Drug-Induced↗

Distribution of blood flow in the muscles of conscious animals during exercise.

This study reviews the recent research on the distribution of blood flow within and among skeletal muscles in conscious animals during locomotory exercise. A brief description of the technique that has been used in these studies, the radiolabeled microsphere method, is presented, including a short discussion of the assumptions that must be met in using the methodology. Distinct patterns of flow distribution occur in the muscles during exercise that are related to the fiber-type composition of the muscles or muscle parts (and, presumably, the patterns of fiber recruitment) and the intensity of the exercise. The mechanisms that regulate the differential elevations in blood flow within and among the muscles at the initiation of exercise have not been elucidated. However, studies on the conscious animal model indicate that the control cannot be totally explained by local metabolic factors, sympathetic influences or mechanical effects.

Animals↗

Distribution of microspheres in plantaris muscles of resting and exercising rats as a function of fiber type.

The purpose of this study was to determine histologically the distribution of microspheres (MSs) (14 micron), and hence the relative distribution of blood flow, in rat plantaris muscle relative to the fiber types (fast-twitch-oxidative-glycolytic [FOG], fast-twitch-glycolytic [FG], and slow-twitch-oxidative [SO]). Three conditions were investigated: 1) preexercise standing; 2) treadmill locomotion at 15 m/min (fast walking); and 3) treadmill locomotion at 60 m/min (moderate galloping). The MS suspension (containing 1 x 10(6) MSs) was infused into the ascending aorta via a catheter in the carotid artery under each of the 3 conditions so that MSs were distributed to the tissues in proportion to their respective blood flows. Sections (20 micron) of the plantaris muscle were cut and assayed for reduced nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) and myofibrillar adenosine triphosphatase (ATPase) activities so the fibers could be typed as SO, FOG, or FG. MSs were located in the NADH-TR sections, and the fibers next to the MSs were classified and counted. The observed numbers of fibers of each type in each condition that were adjacent to MSs were compared to the predicted number of adjacent fibers based on the assumption the MSs were randomly distributed in the tissue. This analysis demonstrated that MSs (and blood flows) were preferentially distributed to SO fibers during preexercise, to SO and FOG fibers during slow locomotion, and to FOG fibers during fast locomotion. The data support the contention that blood flow is distributed in muscles of conscious animals as functions of fiber type and exercise intensity.

Adenosine Triphosphatases↗

Lesions in the rat soleus muscle following eccentrically biased exercise.

Morphological changes in skeletal muscle related to lengthening (eccentric) contractions have been noted by several laboratories. However, a systematic examination of skeletal muscle following repetitive eccentric contractions is lacking. This study was undertaken to study lesions and determine their relative densities in rat soleus muscle 30 min following level or downhill treadmill exercise. Following fixation in situ by vascular perfusion, toluidine-blue-stained 1-micron sections of the muscle samples selected at 73-micron intervals were scanned with a light microscope. Three types of lesions were noted: focal disruptions in the A-band, localized dissolution of Z-lines, and clotting of muscle fibers. Soleus muscle from the caged controls and the tibialis anterior muscle from downhill-exercised rats were essentially free of lesions. Eighty-nine percent of the soleus m. lesions in the downhill runner group and 97% of those in the level runner group were A-band disruptions. A-band lesion density was significantly higher in the soleus muscle of the downhill runners compared to level runners with the highest incidence in the distal half. A-band lesion density was lower in soleus muscles from level runners; however, the highest intramuscular incidence was in the proximal rather than the distal end. The results indicate that a disruption of the A-band is a principal change within some skeletal muscle fibers 30 min following repetitive eccentric contractions.

Animals↗

Open-field behavior is not related to treadmill performance in exercising rats.

We examined the association between open-field behavior and treadmill performance in 39 adult male Sprague-Dawley rats. Three daily, five-minute trials were conducted in an open field of 49 19 cm squares. The objectivity of the open-field test was established by intraclass correlations (R) for observer agreement on total squares traversed (R = .99) and a subjective behavioral rating scale for anxiety (R = .92). As expected, total squares were inversely correlated (r = -.86) with the subjective anxiety ratings. An independent observer also rated animals on treadmill performance across six daily, five-minute trials of level running at 15 m/min. Performance ratings were objective (rs = .89) and reproducible (R = .91). A volitional endurance run at 30 m/min on level grade was also conducted on a subsequent day. Extreme groups of low anxious (N = 7) and high anxious (N = 7) animals were then identified from convergent responses on total square traversals and the subjective behavioral ratings that were reproducible (R = .72 to .78) of trials two and three of the open-field test. Repeated measures ANOVA showed no group differences (p greater than 0.10) on mean treadmill performance across trials. Endurance was also the same for each group (p greater than 0.05). Our findings indicate that the open-field test is objective and reliable, and it does not reveal a selection bias effect on treadmill performance or endurance. Thus, open-field behavior can be used as a dependent or subject-matching variable in studies of adult male Sprague-Dawley rats when motor-driven treadmill running is a behavioral intervention or outcome measure.

Animals↗

Blood flow in normal and denervated muscle during exercise in conscious rats.

The purpose of this study was to test the hypothesis that extrinsic mechanical factors, i.e., the dynamic shortening and lengthening imposed on a muscle during limb movements and the rhythmic compressions as surrounding muscles contract and relax, contribute to the initial muscle hyperemia during locomotion in conscious male Sprague-Dawley rats. Soleus and lateral head of gastrocnemius muscles were surgically denervated in one hindlimb several hours before exercise to remove 1) local metabolic vasodilator effects, 2) vasoconstrictor or vasodilatory influences mediated through sympathetic postganglionic fibers, and 3) intrinsic mechanical pumping. Blood flow was measured with radioactive microspheres during preexercise and at 30 s and 5 min of exercise in rats walking at 15 m/min or a motor-driven treadmill. Glycogen concentrations were also measured as an indicator of muscular activity to verify the denervation. Blood flows to control muscles in the normal limb were similar to previously reported values during preexercise and exercise. Denervation, however, decreased preexercise blood flow (69-88%) to muscle composed predominantly of oxidative fibers and increased flow (53%) to muscle composed predominantly of glycolytic fibers. During exercise, blood flow to denervated muscles either remained unchanged or decreased. These data suggest that extrinsic mechanical factors do not significantly contribute to the initial hyperemic response at the onset of low-intensity exercise in normal muscle.

Animals↗

Systemic adenosine deaminase administration does not reduce active hyperemia in running rats.

The importance of adenosine in controlling the magnitude and distribution of blood flow among and within skeletal muscles in rats during slow locomotor exercise was tested by systemic infusion of adenosine deaminase (ADA). Blood flows were measured using labeled microspheres before exercise and at 0.5, 15, and 30 min of fast treadmill walking at 15 m/min. An initial infusion of ADA (1,000 U/kg) was given 30 min before the first blood flow measurement and a second injection (1,000 U/kg) was given 5 min into exercise. These infusions maintained ADA activity above 5 U/ml blood throughout the experimental period. This plasma concentration of ADA was shown to be sufficient to result in a 64% decrease in muscle adenosine levels during ischemic contraction. Blood flows were measured in all of the muscles of the hindlimb (28 samples) and in various nonmuscular tissues in ADA-treated and control rats. Preexercise blood flows were primarily directed to slow-twitch muscles and exercise blood flows were highest in muscles with fast-twitch oxidative fibers. ADA treatment did not reduce total muscle blood flow or exercise blood flows in any of the muscles at any time. These findings do not support the hypothesis that adenosine plays an essential role in controlling muscle blood flow in skeletal muscles during normal locomotor activity.

Adenosine Deaminase↗

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.

Animals↗

Sympathetic neural influences on muscle blood flow in rats during submaximal exercise.

These experiments were designed to estimate the involvement of the sympathetic innervation in regulation of hindlimb muscle blood flow distribution among and within muscles during submaximal locomotory exercise in rats. Blood flows to 32 hindlimb muscles and 13 other selected tissues were measured using the radiolabeled microsphere technique, before exercise and at 0.5, 2, 5, and 15 min of treadmill exercise at 15 m/min. The two groups of rats studied were 1) intact control, and 2) acutely sympathectomized (hindlimb sympathectomy accomplished by bilateral section of the lumbar sympathetic chain and its connections to the spinal cord at L2-L3). There were no differences in total hindlimb muscle blood flow among the two groups during preexercise or at 30 s or 2 min of exercise. However, flow was higher in eight individual muscles at 2 min of exercise in the sympathectomized rats. At 5 and 15 min of exercise there was higher total hindlimb muscle blood flow in the denervated group compared with control. These differences were also present in many individual muscles. Our results suggest that 1) sympathetic nerves do not exert a net influence on the initial elevations in muscle blood flow at the beginning of exercise, 2) sympathetic nerves are involved in regulating muscle blood flow during steady-state submaximal exercise in conscious rats, and 3) these changes are seen in muscles of all fiber types.

Animals↗

Magnitude and distribution of muscle blood flow in conscious animals during locomotory exercise.

A large number of papers in the literature have reported peak blood flows in electrically stimulated isolated skeletal muscles in the range of 40-140 ml.min-1.100 g-1. Peak muscle blood flows of similar magnitude have been measured in human subjects with 133Xe clearance and plethysmography. In contrast, measurements of average blood flow in conscious animals at VO2max with radiolabeled microspheres have ranged from about 150-250 ml.min-1.100 g-1. Furthermore, flows in active high oxidative muscles in conscious animals during maximal exercise may attain 500 ml.min-1.100 g-1. Reasons for these apparent discrepancies are unknown, but possible explanations including technical artifacts and differences in mechanical influences on contracting muscles in isolated preparations and exercising conscious animals are discussed. It is concluded that the primary reason for the differences in magnitude of muscle blood flow is the efficient muscle pumping action that occurs in vivo during locomotory exercise.

Animals↗

Distribution of blood flow in muscles of miniature swine during exercise.

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.

Animals↗

Adrenoreceptor effects on rat muscle blood flow during treadmill exercise.

The purpose of this study was to examine the effects of the adrenergic receptors on the distribution of blood flow within and among skeletal muscles in rats. Blood flow was measured with the radiolabeled microsphere technique before exercise and during treadmill exercise at 15 or 60 m/min. Alpha- (phentolamine) or beta- (propranolol) adrenergic blocking drugs were administered, and then blood flow was measured and results compared with those from saline-treated rats. Before exercise, alpha-blockade caused increases in total muscle blood flow and in all fast-twitch muscles, whereas muscles composed of greater than 20% slow-twitch fibers showed no effect. During exercise at 15 m/min, the normal increase in total muscle blood flow was attenuated by alpha-blockade. Compared with controls, blood flow was less in the high-oxidative (fast and slow) muscle fiber areas of extensor muscles, whereas blood flow to white areas of extensor muscles was increased. beta-Blockade tended to decrease muscle blood flow before exercise and during exercise at 15 m/min with no apparent relationship between the effects of blockade on blood flow and muscle fiber type. These effects of beta-blockade were not apparent during exercise at 60 m/min. We conclude that before exercise alpha-receptor effects are limited to fast muscle, whereas beta-receptor influences are independent of fiber type, beta-receptors contribute to the initial hyperemia of exercise at 15 m/min, and beta-receptor influence is inversely related to metabolic rate.

Adrenergic alpha-Antagonists↗

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.

Animals↗

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.

Animals↗

Effect of continued ultraviolet B phototherapy on the duration of remission of psoriasis: a randomized study.

Phototherapy using sunburn spectrum ultraviolet radiation (UVB) is now a frequently utilized treatment for psoriasis that is extensive or has not responded to topical preparations. Four university centers performed a prospective randomized clinical trial to compare remission times of patients with psoriasis who continued UVB phototherapy after initial clearing with this therapy and patients whose UVB phototherapy was discontinued within 3 weeks of clearing. As assessed by life table methods, the time to flare after initial clearing for patients on UVB maintenance therapy was significantly longer than for patients who discontinued UVB within 3 weeks after initial clearing. Our data suggest that continuing UVB phototherapy after initial clearing contributes to the duration of disease control and is justified for many patients.

Actuarial Analysis↗

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.

Animals↗

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.

Animals↗