Biomedical subjects

S L Dodd

Publications and source records attributed to S L Dodd.

At least 19 recordsLinked to original sources

PubMed1998

Effects of intermittent ischemia on contractile properties and myosin isoforms of skeletal muscle.

PURPOSE: This study determined the effects of intermittent ischemia on the contractile properties, fatigue (Tf), and myosin heavy chain composition (MHC) in the rat gastrocnemius-plantarissoleus muscle (GPS) complex. METHODS: Fifty rats were divided into four groups: control (C, N = 12), severed (femoral artery) (S, N = 12), exercise (E, N = 13), and severed/exercise (SE, N = 13). Ischemia was elicited only in the SE group by daily exercise and the other groups served as controls. Exercise in the E and SE groups consisted of running on a treadmill approximately 35 min.d-1, 5 d.wk-1 for 7 wk. RESULTS: Body weight, muscle weight, and absolute force were less in the SE group compared with those in C (12, 18, and 12% respectively). However, relative force (N.g-1 of muscle) was greater in the SE group compared with that in C (8%). Maximal shortening velocity (Vmax) was lower in the SE group compared with that in all others (10-14%). Tf was less in the S group compared with that in C and E (28 and 30%, respectively). Type IIx MHC increased and type IIb decreased in gastrocnemius and plantaris muscles in SE compared with those in C. CONCLUSIONS: These data indicate that intermittent ischemia caused a decrease in muscle mass, maximal force development, and Vmax, but had no effect on Tf. The decrease in Vmax may have been related to myosin alterations in the muscles.

Animals↗

PubMed1997

Mechanism of specific force deficit in the senescent rat diaphragm.

Aging is associated with a decline in the maximal in vitro specific force in the rat costal diaphragm. The purpose of this study was to determine if this force deficit is associated with a decrease in the concentration of myofibrillar protein in diaphragm fibers of senescent rats. Isometric twitch and tetanic contractile properties were measured on diaphragm strips from young adult (9-month-old: n = 12) and senescent (26-month-old: n = 13) male specific pathogen free-barrier protected Fischer 344 rats. Maximal tetanic force (Po) normalized to the cross-sectional area (CSA) of the in vitro diaphragm strips was 16.4% lower in the senescent diaphragms (21.03 +/- 0.4 N/cm2) compared to the young adult (25.16 +/- 0.5 N/cm2) (p < 0.001). Diaphragm water content was significantly higher in the senescent group (75.9% of total wet mass) compared to the young adult (72.1% of total wet mass, p < 0.05). Subtracting the contribution of water from the CSA of the diaphragm strips significantly reduced (p < 0.05) the senescent specific Po deficit (from -16.4 to -6.4%). Further, correcting Po for the contribution of myofibrillar protein to CSA resulted in no age group differences in specific force. These data indicate that the age-related decline in diaphragm in vitro maximal specific Po can be explained by an age-related increase in the water content of the diaphragm muscle. Future experiments are necessary to determine the mechanism(s) responsible for this observation.

Aging↗

PubMed1997

Bioenergetic characteristics of the costal and crural diaphragm in mammals.

These experiments compared oxidative and glycolytic enzyme activity in the costal and crural diaphragm in seven adult mammals (mouse, rat, rabbit, ferret, sheep, pig, cow) ranging in body mass from approximately 0.03 to 422 kg. Segments of the costal and crural diaphragm from the aforementioned species were homogenized to determine the activities of the glycolytic enzyme, lactate dehydrogenase (LDH), and the Krebs cycle enzyme, citrate synthase (CS). The results indicated that metabolic differences between the costal and crural diaphragm do not exist in all mammalian species. Specifically, CS activity differed (P < 0.05) between the costal and crural diaphragm (costal approximately 36% greater than crural) in only two species (rat and rabbit). Further, the oxidative capacity of the costal and crural diaphragm was significantly correlated with both breathing frequency and resting metabolic rate (r = 0.92 - 0.57; P < 0.05) across the species investigated. In contrast, glycolytic capacity was not significantly correlated (P > 0.05) with either breathing frequency or resting metabolic rate.

Animals↗

PubMed1996

Effects of clenbuterol on contractile and biochemical properties of skeletal muscle.

We investigated the effects of clenbuterol on the muscle mass, contractile properties, myosin phenotype, and bioenergetic enzyme activity in the gastrocnemius (GS)-plantaris (PL)-soleus (SO) muscle complex. Rats were sham-injected or treated with clenbuterol (2 mg.kg-1, subcutaneously) for 14 d. Clenbuterol increased (P < 0.05) body weight and muscle complex weight. Also, clenbuterol treatment resulted in an increase in total muscle force production and maximal shortening velocity (P < 0.05). No difference (P > 0.05) in relative force production (force.g-1 muscle) existed between experimental groups. However, muscle fatigue increased with clenbuterol treatment. Myosin heavy chain (MHC) composition was not altered in the GS or PL muscles, but shifted toward the fast Type II MHC in the SO. Myosin light chain (MLC) composition was not altered in any of the muscles. Clenbuterol caused a decrease in oxidative and glycolytic enzyme activity in the GS and PL, but not the SO. These data suggest that the clenbuterol-induced increase in muscle mass and maximal force generation is due to hypertrophy of both fast and slow fibers. Furthermore, these findings support the notion that beta-agonists may be beneficial in combating conditions that result in muscle wasting and dysfunction.

Adrenergic beta-Agonists↗

PubMed1996

Alterations in phenotypic and contractile properties of the rat diaphragm: influence of hypothyroidism.

This study examined the influence of experimental hypothyroidism on myosin isoform distribution and contractile function of the costal diaphragm. Adult female Sprague-Dawley rats were randomly assigned to control (n = 12) or hypothyroid groups (n = 13) over a 6-wk treatment period. In comparison to the control group, in the hypothyroid group the relative distribution of type I myosin heavy chain (MHC) was increased 35% (P < 0.05), whereas type IIb MHC decreased 63% (P < 0.05). Similarly, Ca(2+)-activated myosin adenosinetriphosphatase activity (nmol Pi.mg-1.min-1) in the hypothyroid group was reduced 30% compared with the control group (P < 0.05). Furthermore, significant reductions in diaphragmatic maximal tetanic specific tension (Po; N.cm-2; -21%) and maximal shortening velocity (Vmax; muscle length/s; -25%) were observed in the hypothyroid group. These data provide the first evidence that hypothyroid produces a fast-(type IIb) to-slow (type I) shift in costal diaphragmatic MHC isoform profile that is highly correlated to the observed decrease in Vmax. Finally, the present findings indicate that hypothyroidism does not alter myofibrillar content or noncontractile elements of the diaphragm, thereby suggesting an alternative mechanism(s) to explain the reduction in specific Po.

Animals↗

PubMed1996

Effects of aging and obesity on respiratory muscle phenotype in Zucker rats.

Because obesity results in an increased work of breathing, we tested the hypothesis that the oxidative properties and myosin heavy chain (MHC) isoform profiles in respiratory muscles would differ between lean and obese animals. Furthermore, we postulated that obesity-related changes in respiratory muscles would be independent of age. To test these hypothesis, samples of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles were removed from three age groups (young, adult, and old) of obese and lean Zucker rats. Citrate synthase (CS) activity was measured as a marker of oxidative capacity, and MHC isoforms were identified with gel electrophoresis. Analysis revealed that CS activity was significantly higher in the crural and costal diaphragms and parasternal intercostal of obese animals compared with lean animals (P < 0.05); this obesity-related increased in CS activity was related independent of age. Furthermore, respiratory muscle percent type IIb MHC was lower and percent type I MHC isoforms were higher in obese animals compared with lean animals. These data support the notion that obesity results in a fast-to-slow shift in MHC phenotype and an increase in oxidative capacity in major inspiratory muscles. The shift in MHC isoforms in obese animals is also age related, whereas the obesity-mediated increase in oxidative capacity is relatively independent of age.

Aging↗

PubMed1996

The effects of hypothyroidism on single fibers of the rat soleus muscle.

Skinned single fibers were used to test the hypothesis that skinned fibers from hypothyroid soleus muscle would have a higher sensitivity to calcium compared with control fibers, as indicated by a leftward shift of the pCa-force curve. Control rats (n = 14) received sham injections, while the hypothyroid group (n = 16) received thyroidectomy and a 6-week injection period of the antithyroid drug 6-n-propyl-2-thiouracil. Hypothyroidism caused the type I fiber number to increase significantly (11%) in the soleus. Hypothyroid fibers produced 16% less absolute tension than control fibers. However, cross-sectional areas of control fibers were significantly greater (25%) than those of hypothyroid fibers, so that when force was normalized to cross-sectional area, no differences between groups existed. Calcium requirement for half-maximal force production (pCa50) did not differ, but the slope of the pCa-force curve was different between groups. These data suggest that hypothyroidism did not alter the intrinsic force-generating capacity of the soleus muscle fibers. Thus, alterations in hypothyroid soleus contractile function seen in vitro may be explained by alterations in excitation-contraction coupling and (or) shifts in muscle fiber types.

Animals↗

PubMed1995

Interaction of glucocorticoids and activity patterns affect muscle function.

The purpose of this study was to determine the effects of glucocorticoids on muscle mass and contractile properties of muscles of similar fiber composition but differing in activity patterns. Rats were divided into two groups and administered prednisolone (5 mg/kg per day) (P; N = 9) or served as controls (C; N = 10) for 10 days. Contractile properties were then determined in the left gastrocnemius-plantaris-soleus (GPS) muscle complex and a strip of costal diaphragm (D). An index of fatigue was also determined in both muscle preparations. Whole-body, GPS, and D weights decreased (P < 0.05) in the P animals (22%, 17%, and 15%, respectively) when compared to C. Specific tension (PO) increased (P < 0.05) in the GPS complex (21%) and decreased in the D (26%). Maximal shortening velocity (Vmax) was not different (P > 0.05) between groups in either the GPS or the D. While the index of fatigue was not different (P > 0.05) between groups in the D, there was a 30% increase (P < 0.05) in the rate of fatigue in the GPS. These data indicate that, although glucocorticoids cause decreased muscle mass in both D and GPS, a change in muscle architecture may prevent a decrease in force-generating ability in some limb muscles. However, glucocorticoids do not increase D fatigability as seen in the GPS.

Animals↗

PubMed1994

Tension development and duty cycle affect Qpeak and VO2peak in contracting muscle.

Ten canine gastrocnemius-plantaris muscle preparations were stimulated in situ to determine the interaction between tension development and the duty cycle in determining Qpeak and VO2peak. The muscle was stimulated with supramaximal voltage using four different stimulation protocols: 1) 5 twitches.s-1 (Tw), 2) 1 train.s-1-200 ms (1-200), 3) 1 train.s-1-300 ms (1-300), and 4) 2 trains.s-1-100 ms (2-100). Arterial and venous blood were sampled and Qpeak measured for determination of VO2peak. The total tension developed per second was integrated and averaged over 1 s (TDa) and used as an index of work of the muscle for each condition. The Qpeak and VO2peak were greater (P < 0.05) in the 1-200 condition compared to all other conditions. Further, Qpeak and VO2peak were greater (P < 0.05) in both the 1-300 and 2-100 conditions than during Tw: Qpeak (ml.kg-1.min-1) (mean +/- SE) for (Tw) = 928 +/- 65; (1-200) = 1368 +/- 102; (1-300) = 1150 +/- 96; (2-100) = 1189 +/- 89; VO2peak (ml.kg-1.min-1) for (Tw) = 108 +/- 8; (1-200) = 159 +/- 9; (1-300) = 135 +/- 11; (2-100) = 137 +/- 8. The TDa was significantly different among all conditions: TDa (N.kg-1) for (Tw) = 443 +/- 56; (1-200) = 606 +/- 81; (1-300) = 722 +/- 79; (2-100) = 522 +/- 41. We interpret these findings as an indication that the interaction of the duty cycle and tension development is a prime determinant of blood flow during muscle contractions.

Animals↗

PubMed1993

Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle.

This investigation was designed to describe alterations in O2 uptake (VO2) and tension development in a contracting in situ gastrocnemious-plantaris muscle preparation during three conditions of reduced O2 delivery [arterial O2 concentration X blood flow (Q)]. The three conditions, hypoxemia (H), ischemia (I), and anemia (A), were matched for O2 delivery. A normoxic normal flow condition was also utilized for comparison. H was produced by respiring the animals with 9% O2 in N2; I was produced by lowering Q, and A was produced by hemodilution with 6% dextran. The stimulation pattern for the isometric tetanic contractions used was 1 train/s, and each train was 200 ms, 70 Hz, and 6 V. The muscle was maximally contracted during each of the experimental conditions, and the conditions were administered in random order. In each bout the contractions continued for 5 min with 30 min of rest between bouts. Samples of arterial and muscle venous blood were obtained during the last 30 s of each bout. VO2 during I (125 ml.kg-1.min-1) was less than during N (145 ml.kg-1.min-1; P < 0.05) and greater than during H or A (104 and 101 ml.kg-1.min-1, respectively; P < 0.05). Venous PO2 (PVO2) was significantly lower during H (17.1 Torr) compared with the other conditions; no differences existed between N, I, and A (26.8, 26.0, and 28.1 Torr, respectively). Tension development was reduced by the reduction of O2 delivery during I, H, and A compared with N. Tension developed among the reduced O2 delivery groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

PubMed1993

Caffeine and exercise performance. An update.

Three principal cellular mechanisms have been proposed to explain the ergogenic potential of caffeine during exercise: (a) increased myofilament affinity for calcium and/or increased release of calcium from the sarcoplasmic reticulum in skeletal muscle; (b) cellular actions caused by accumulation of cyclic-3',5'-adenosine monophosphate (cAMP) in various tissues including skeletal muscle and adipocytes; and (c) cellular actions mediated by competitive inhibition of adenosine receptors in the central nervous system and somatic cells. The relative importance of each of the above mechanisms in explaining in vivo physiological effects of caffeine during exercise continues to be debated. However, growing evidence suggests that inhibition of adenosine receptors is one of the most important, if not the most important, mechanism to explain the physiological effects of caffeine at nontoxic plasma concentrations. Numerous animal studies using high caffeine doses have reported increased force development in isolated skeletal muscle in both in vitro and in situ preparations. In contrast, in vivo human studies have not consistently shown caffeine to enhance muscular performance during high intensity, short term exercise. Further, recent evidence supports previous work that shows caffeine does not improve performance during short term incremental exercise. Although controversy exists, the major part of published evidence evaluating performance supports the notion that caffeine is ergogenic during prolonged (> 30 min), moderate intensity (approximately 75 to 80% VO2max) exercise. The mechanism to explain these findings may be linked to a caffeine-mediated glycogen sparing effect secondary to an increased rate of lipolysis.

Animals↗

PubMed1991

The effects of caffeine on graded exercise performance in caffeine naive versus habituated subjects.

The physiological effects of caffeine on subjects habituated to caffeine is relatively unstudied compared to those of caffeine naive subjects during graded exercise. Thus, the purpose of this investigation was to determine the effects of caffeine on maximal oxygen consumption (VO2max) and the anaerobic threshold in these two populations. Seventeen moderately trained males were classified according to caffeine usage: (1) caffeine consumption 25 mg.day-1 or less (CN) (n = 8) or (2) caffeine consumption above 300 mg.day-1 (CH) (n = 9). The subjects were tested post-absorptive on the same cycle ergometer on three occasions with 7 days separating the tests. One hour before each test the subject ingested either a gelatin capsule (C); 3 mg.kg-1 body weight of caffeine (C3); or 5 mg.kg-1 body weight of caffeine (C5). The subject then performed an incremental VO2max test beginning at 50 W and the work rate was increased 30 W every 2 min until the subject could not maintain the power output. Serial venous blood samples were drawn over 30 s at the end of each stage. The CN group significantly increased resting heart rate (fc) and expired ventilation volume (VE) after C3 and C5 and VO2 after C5. No significant differences were found for exercise VE, VO2, respiratory exchange ratio, fc or time to exhaustion. There were no significant differences (P less than 0.05) in the lactate threshold or the ventilatory threshold between treatment in either group. The CH subjects showed a significant increase (P less than 0.05) in resting plasma free fatty acid (FFA) concentration only during the C3 and C5 treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Exercise performance following intense, short-term ventilatory work.

Evidence exists to indicate that prolonged ventilatory work fatigues respiratory muscles and may limit exercise tolerance. However, the effects of short-duration, high-intensity ventilatory work on subsequent exercise remains in question. We tested the hypothesis that intense short-term volitional hyperpnea would result in respiratory muscle fatigue and would therefore hinder subsequent exercise tolerance. Pulmonary function was determined in ten healthy, male subjects before and after two constant load exercise tests to exhaustion on a cycle ergometer. Test 1 was a preliminary test to determine VO2max, peak exercise VE, and peak exercise power output. Test 2 was a constant load (85% peak power output) exercise test to exhaustion. Test 3 was identical to test 2 but was preceded by 10 min of volitional, isocapnic hyperpnea (85% of peak exercise V.E) at a controlled frequency and tidal volume. Pulmonary function measures (FVC, FEV1, FEV1/FVC, and peak flow) were not significantly (P less than 0.05) altered by the volitional hyperpnea. Ventilation and gas exchange variables (VO2, VE, f, end-tidal PO2 and PCO2, VE/VO2, VE/VCO2, %SaO2) during exercise and time to exhaustion were not significantly (P less than 0.05) different between treatments. These experiments failed to show any effect of short-term ventilatory work on pulmonary function or subsequent exercise performance.

Adult↗

PubMed1989

Regional hemodynamic responses to hypoxia and hypermetabolism in polycythemic dogs.

Normovolemic polycythemia did not improve the ability of either resting muscle or gut to maintain O2 uptake (VO2) during severe hypoxia because of the adverse effects of increased viscosity on blood flow to those regions. The present study tested whether increased metabolic demand would promote vasodilation sufficiently to overcome those effects. We measured whole body, muscle, and gut blood flow, O2 extraction, and VO2 in anesthetized dogs after increasing hematocrit to 65% and raising O2 demand with 2,4-dinitrophenol (n = 8). We also tested whether regional denervation (n = 8) and hypervolemia (n = 6) affected these responses. After raising hematocrit and metabolism, the dogs were ventilated with air, with 9% O2-91% N2, and again with air for 30-min periods. Reduced blood flow and increased O2 demand, caused by increased blood viscosity and 2,4-dinitrophenol, respectively, increased O2 extraction so that muscle VO2 was nearly supply limited in normoxia. Denervation showed that vasoconstriction had increased in gut and muscle with hypoxia onset but this was overcome after 15 min. By then, muscle was receiving a major portion of cardiac output, whereas gut showed little change. With hypervolemia cardiac output increased in hypoxia but neither gut nor muscle increased blood flow in those experiments. Because regional and whole body VO2 fell in all groups during hypoxia to the same extent found earlier in normocythemic dogs, any real benefit of polycythemia under the conditions of these experiments was dubious at best.

Animals↗

PubMed1987

Responses of innervated and denervated gut to whole-body hypoxia.

As a significant user of O2 at rest (20% of whole body), the gut may be subject to more severe limitation of O2 supply during global hypoxia than more vital areas because of preferential redistribution of blood flow. Accordingly, its accumulation of O2 deficit during hypoxia and its excess O2 use during normoxic recovery might be altered by extrinsic neural activity. We measured blood flow and O2 uptake in whole body (WB) and gut segments while anesthetized dogs were ventilated with 9% O2-91% N2 for 30 min followed by 30-min normoxic recovery. In six dogs extrinsic innervation to the gut segment was left intact and it was severed in another six animals. O2 deficit and excess were the accumulated differences from the normoxic O2 uptake for both gut and WB corrected for O2 stores changes. The intact gut, although only 4% body wt, incurred 22% of WB O2 deficit but contributed only 8% to WB O2 excess. The imbalance (gut excess was only 44% of gut deficit) implied that O2 using functions were curtailed during hypoxia without obligating an energy stores deficit. Denervation did not alter these quantitative relationships. Blood flow responses to transition between normoxia and hypoxia were only transiently altered. Extrinsic innervation apparently plays no major role in gut responses to WB hypoxia.

Animals↗

PubMed1987

Muscle O2 deficit during hypoxia and two levels of O2 demand.

We have examined the relative deficits in tension development and O2 uptake in contracting skeletal muscle during severe hypoxic hypoxia. Anesthetized mongrel dogs were ventilated to maintain an end-tidal PCO2 between 35 and 40 Torr. Venous outflow from the gastrocnemius muscle was measured using an electromagnetic flow probe. The tendon was cut and attached to a strain gauge. The muscle was stimulated to contract isometrically at 2 or 4 Hz for 20 min. Hypoxia (9% O2 in N2) was then imposed for 30 min, followed by 30 min of normoxia. Blood flow first increased in proportion to the contraction frequency and then increased further a similar amount in both groups during hypoxia. O2 extraction and blood flow reached maximal levels during hypoxia in the 2-Hz group. The further O2 deficit that was accumulated during 4 Hz and hypoxia was, therefore, a result of the greater discrepancy between O2 supply and demand. O2 uptake decreased more in hypoxia than did developed tension. These results are best explained by ATP supplementation from nonaerobic energy sources that was promoted by the free-flow condition of hypoxic hypoxia.

Animals↗

PubMed1987

Systemic and intestinal limits of O2 extraction in the dog.

When systemic delivery of O2 (QO2 = QT X CaO2, where QT is cardiac output and CaO2 is arterial O2 content) is reduced by bleeding, the systemic O2 extraction ratio [ER = (CaO2 - CVO2)/CaO2, where CVO2 is venous O2 content] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by O2 delivery. During hypovolemia, reflex increases in mesenteric arterial tone may preferentially reduce gut blood flow so that the onset of O2 supply dependence occurs in the gut before other regions. We compared the critical O2 delivery (QO2c) and critical extraction ratio (ERc) of whole body and an isolated segment (30-50 g) of small bowel in seven anesthetized paralyzed dogs ventilated with room air. Systemic QO2 was reduced in stages by controlled hemorrhage as arterial O2 content was maintained, and systemic and gut VO2 and QO2 were measured at each stage. Body QO2c was 7.9 +/- 1.9 ml X kg-1 X min-1 (ERc = 0.69 +/- 0.12), whereas gut O2 supply dependency occurred when gut QO2 was 34.3 +/- 11.3 ml X min-1 X kg gut wt-1 (ERc = 0.63 +/- 0.09). O2 supply dependency in the gut occurred at a higher systemic QO2 (9.7 +/- 2.7) than whole-body QO2c (P less than 0.05). The extraction ratio at the final stage (maximal ER) was less in the gut (0.80 +/- 0.05) than whole body (0.87 +/- 0.06). Thus during reductions in systemic QO2, gut VO2 was maintained by increases in gut extraction of O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

O2 delivery to contracting muscle during hypoxic or CO hypoxia.

The consequences of a decreased O2 supply to a contracting canine gastrocnemius muscle preparation were investigated during two forms of hypoxia: hypoxic hypoxia (HH) (n = 6) and CO hypoxia (COH) (n = 6). Muscle O2 uptake, blood flow, O2 extraction, and developed tension were measured at rest and at 1 twitch/s isometric contractions in normoxia and in hypoxia. No differences were observed between the two groups at rest. During contractions and hypoxia, however, O2 uptake decreased from the normoxic level in the COH group but not in the HH group. Blood flow increased in both groups during hypoxia, but more so in the COH group. O2 extraction increased further with hypoxia (P less than 0.05) during concentrations in the HH group but actually fell (P less than 0.05) in the COH group. The O2 uptake limitation during COH and contractions was associated with a lesser O2 extraction. The leftward shift in the oxyhemoglobin dissociation curve during COH may have impeded tissue O2 extraction. Other factors, however, such as decreased myoglobin function or perfusion heterogeneity must have contributed to the inability to utilize the O2 reserve more fully.

Animals↗