PubMed HealthSearch

Biomedical subjects

K E Conley

Publications and source records attributed to K E Conley.

16 recordsLinked to original sources

Minimal cost per twitch in rattlesnake tail muscle.

Sound production is one of the most energetically costly activities in animals. Minimizing contraction costs is one means of achieving the activation rates necessary for sound production (20-550 Hz) (refs 1-3) without exceeding energy supplies. Rattlesnakes produce a sustained, high-frequency warning sound by extremely rapid contraction of their tailshaker muscles (20-90 Hz) (refs 4,5). The ATP cost per twitch is only 0.015 micromol ATP per g muscle per twitch during rattling, as measured by in vivo magnetic resonance. The reduced volume density of myofibre (32%) in tailshaker muscle is consistent with contraction cost being minimized (crossbridge cycling), in contrast to the contractile costs of vertebrate locomotory and asynchronous insect flight muscle. Thus tailshaker muscle is an example of sound-producing muscle designed for 'high frequency, minimal cost'. The high rates of rattling are achieved by minimizing contractile use of ATP, which reduces the cost per twitch to among the lowest found for striated muscle.

Adenosine Triphosphate

Functional training: muscle structure, function, and performance in older women.

Response to physical training at the cellular and whole muscle level has been established in older adults. However, the underlying molecular mechanism responsible for change has not been described nor have the relationships between change in muscle structure and functional performance been established. The purpose of this research study is to evaluate the changes of muscle ultrastructure, muscle strength, and whole body functional performance as a result of a functionally directed exercise program (stair climbing). Women (65-83 years old) selected either the control (no exercise; N = 6) or exercise (N = 7) group. The 1-year functionally based exercise program was both aerobic (75% heart rate reserve) and resistive (weighted stair climbing). Muscle ultrastructure, determined by quantitative morphometry of the vastus lateralis tissue, and maximal step-height achieved by each subject were related to isokinetic strength and muscle morphology. Changes in myofibrillar area accounted for 48% of the variance in muscle strength changes. Change in muscle contractile protein was the underlying basis for change in thigh strength which, in turn, was the basis for functional performance. These data provide evidence that, in older women, a mild functionally based training program results in improved muscle structure and performance of the lower body.

Aged

From muscle properties to human performance, using magnetic resonance.

Our goal is to show how muscle properties can be used to understand the exercise performance limitations of the elderly. We show that magnetic resonance (MR) imaging and spectroscopy are useful for noninvasively characterizing the structural and energetic properties of muscle in vivo. Determination of muscle volume and cross-sectional area is easily and rapidly accomplished by applying quantitative morphometric methods to MR images. New MR spectroscopic techniques provide a noninvasive "biopsy" of the oxidative, glycolytic, and contractile capacities of muscle fibers. We show how the structural and energetic properties measured by MR can be used to define the functional capacity of muscle and the contribution of this capacity to the performance of the whole body (e.g., VO2max). Finally, we relate these laboratory measures of muscle properties and performance to activities meaningful to the functioning of the elderly in everyday life, such as sustained walking and stair climbing.

Activities of Daily Living

Heart mitochondrial properties and aerobic capacity are similarly related in a mammal and a reptile.

The heart mitochondrial properties and the aerobic capacity (VO2max) of the rat (Sprague-Dawley breed) and the Cuban iguana (Cyclura nubila) were used to evaluate the relationship between the oxidative capacity of the heart and the maximum oxygen delivery rate. Both species are active at body temperatures of 37-39 degrees C, have similar heart mitochondrial volumes [Vmt; 0.43 +/- 0.02 ml (S.E.M.) in the rat and 0.48 +/- 0.02 ml in the iguana] and differ less than twofold in VO2max (29.2 +/- 1.6 and 16.9 +/- 0.6 ml min-1, respectively). We found that Vmt was closely correlated with VO2max in the rat (r2 = 0.77, P < 0.005) and the iguana (r2 = 0.82; P < 0.001). Furthermore, the inner mitochondrial membrane (cristae) area (Sim) per unit VO2max did not differ between the rat and the iguana (0.60 +/- 0.02 and 0.71 +/- 0.02 m2 min ml-1 O2, respectively). This correspondence of Sim/VO2max indicates that the rat and the iguana have the same cardiac oxidative capacity at the maximum oxygen delivery rate. These results suggest that, despite the differences between the cardiovascular systems of these species, the cardiac cost of delivering oxygen at the aerobic capacity is similar in this mammal and this reptile.

Aerobiosis

Cellular energetics during exercise.

How is the muscle fiber designed to accomplish the diversity of tasks performed by striated muscle? Basically, a common contractile mechanism and a similar organization of metabolism in striated muscles are used to generate a wide spectrum of speeds and durations of contraction. The speed of contraction ranges from manyfold within an animal to over a hundred-fold between animals, owing to variation in the intrinsic velocities of the myosin isoforms. Recruiting fibers that contain the myosin isoform that contracts at the appropriate velocity varies the speed of locomotion at minimal cost. The magnitude and duration of the energy supply required to meet this contractile demand depends on the size of the cellular energy buffer and the capacities of the metabolic pathways. The faster the contractile speed, the larger the PCr pool and the greater the glycolytic capacity to meet a high rate of ATP use. Slower-contracting fibers have a smaller buffer for the short term, but an increased oxidative capacity for continuous energy supply to maintain energy balance over the long term. In general, fibers trade contractile speed for duration of performance, but a number of exceptions exist where rapid contractions are maintained for extended periods. In the face of this heterogeneity of properties, common features are found that assure an energy balance. The PCr/ATP buffer system offers a simple mechanism of feedback control of energy supply despite the wide range of high-energy phosphate concentrations and oxidative capacities found in skeletal muscle. An oxygen balance system also appears to be present in the terminal structures of the respiratory system, the capillaries, and mitochondria. Despite the diversity of these structures, a rather constant ratio of oxygen delivery capacity to mitochondrial oxidative capacity is found in vertebrate striated muscles. Finally, a critical feature of muscle energy balance that remains unresolved is (are) the mechanism(s) controlling mitochondrial respiration in heart. Feedback control appears to account for linking ATP supply to demand in skeletal muscle, but the mechanisms governing respiratory control in heart are still under vigorous investigation. Thus, the links between contractile demand and oxidative phosphorylation are still unresolved in this tissue, which may indicate that a key element is missing in our understanding of the cellular energetics of exercise.

Adenosine Triphosphate

Individual variation in contractile cost and recovery in a human skeletal muscle.

This study determined the variation among individuals in ATP use during contraction and ATP synthesis after stimulation in a human limb muscle. Muscle energetics were evaluated using a metabolic stress test that separates ATP utilization from synthesis by 31P NMR spectroscopy. Epicutaneous supramaximal twitch stimulation (1 Hz) of the median and ulnar nerves was applied in combination with ischemia of the finger and wrist flexors in eight normal subjects. The linear creatine phosphate (PCr) breakdown during ischemic stimulation defined ATP use (delta PCr per twitch or approximately P/twitch) and was highly reproducible as shown by the relative standard deviation [(standard deviation/mean) x 100] of 11% in three repeated measures. The time constant of the monoexponential PCr change during aerobic recovery represented ATP synthesis rate and also showed a low relative standard deviation (9%). Individuals were found to differ significantly in both mean approximately P/twitch (PCr breakdown rates, 0.29-0.45% PCr per sec or % PCr per twitch; ANOVA, p < 0.001) and in mean recovery time constants (41-74 sec; ANOVA, P < 0.001). This range of approximately P/twitch corresponded with the range of fiber types reported for a flexor muscle. In addition, approximately P/twitch was negatively correlated with a metabolite marker of slow-twitch fiber composition (Pi/ATP). The nearly 2-fold range of recovery time constants agreed with the range of mitochondrial volume densities found in human muscle biopsies. These results indicate that both components involved in the muscle energy balance--oxidative capacity and contractile costs--vary among individuals in human muscle and can be measured noninvasively by 31 P NMR.

Adenosine Triphosphate

Separate measures of ATP utilization and recovery in human skeletal muscle.

1. The chemical changes during contractile activity were separated from recovery metabolism in the forearm flexor musculature in normal human subjects using 31P nuclear magnetic resonance (NMR) spectroscopy. Percutaneous, supramaximal twitch stimulation of the median and ulnar nerves was used in combination with temporary ischaemia of the forearm to characterize the summed ATPase activity. The recovery following restoration of blood flow provided a measure of oxidative ATP synthesis activity. These processes were measured based on the dynamics of creatine phosphate (PCr) content. 2. Muscle oxygen stores were depleted using ischaemia without stimulation as indicated by PCr breakdown after 250 +/- 33 s (mean +/- S.D.; n = 5), which provided a measure of the basal metabolic rate (0.008 +/- 0.002 mM s-1, n = 5). 3. The PCr breakdown rate during twitch stimulation of the oxygen-depleted muscle was constant at 1 Hz at 0.15 +/- 0.03 mM PCr per second or per twitch (n = 8). A constant cost per twitch was found from 0.5 to 2 Hz stimulation (depletion of PCr per twitch = 0.15 mM per twitch). 4. No net anaerobic recovery of PCr was found during a 2 min post-stimulation ischaemia. 5. Upon restoration of blood flow, PCr recovery followed an exponential time course with a time constant of 63 +/- 14 s (n = 8). From these recovery rates, the capacity for oxidative phosphorylation was estimated to be 0.4 mM s-1. 6. This experimental approach defines a non-invasive and quantitative measure of human muscle ATPase rate and ATP synthetase rate.

Adenosine Triphosphatases

Capillary and mitochondrial unit in muscles of a large lizard.

We asked whether capillaries and mitochondria form a structural and functional unit in the musculature of the Cuban iguana (Cyclura nubila) similar to that found in mammals. We found a significant correlation between capillary length density [Jv(c, f)] and mitochondrial volume density [Vv(mt, f)] of the musculature with a slope that revealed that on average 3.5 km of capillaries were associated with each milliliter of mitochondria (vs. approximately 11 km/ml in mammals). These capillaries had a diameter of 9 microns (vs. 4.5 microns in mammals), and the mitochondria had a surface density of the inner membranes of 25 m2/ml (vs. 30-45 m2/ml in mammals). These dimensions resulted in ratios of capillary to mitochondrial volume (0.22 ml/ml) and capillary wall to mitochondrial membrane surface area (39 cm2/m2) that were similar in Cyclura to those found in mammals (approximately 0.18 ml/ml and 35-52 cm2/m2, respectively). Also in agreement with mammalian values were the average oxidative capacity of the mitochondria derived from maximum rate of O2 consumption (VO2max) during exercise at 37 degrees C and the inner mitochondrial membrane surface area [S(im)] of the musculature [VO2max/S(im) = 0.04 vs. 0.06-0.15 ml O2.m-2.min-1 in mammals]. These common structural and functional relationships support the notion that capillaries and mitochondria represent a similar fundamental unit in muscles of both Cyclura and mammals.

Animals

Oxygen transport during exercise in large mammals. I. Adaptive variation in oxygen demand.

This study investigated mechanisms used by horses and steers to increase O2 uptake and delivery (VO2) from resting to maximal rates and identified the mechanisms that enable horses to achieve higher maximal rates of O2 consumption (VO2max) than steers. VO2 and circulatory variables were measured while Standardbred trotting horses and steers (450-kg body mass) stood quietly and ran on a treadmill at speeds up to those eliciting VO2max. As VO2 increased in both species, heart rate and circulating hemoglobin (Hb) concentration increased, thereby increasing O2 delivery by the circulation, while cardiac stroke volume remained unchanged. At VO2max arterial PCO2 increased from its resting value in horses but was unchanged in steers, and arterial PO2 decreased in both species. Although the horses hypoventilated and were hypoxemic at VO2max, no significant decrease in arterial Hb saturation occurred. VO2max of the horses was 2.6 times higher than that of the steers and was associated with a 100% larger cardiac output, 100% larger stroke volume, and 40% higher Hb concentration, whereas heart rates at VO2max were identical in the two species. The higher cardiac output of the horses at VO2max resulted from a 1.2-fold higher mean arterial pressure and 1.6-fold lower peripheral tissue resistance (associated with a larger skeletal muscle capillary bed). Both the magnitude of the difference in VO2max between horses and steers and the mechanisms used to achieve it are the same as observed in smaller pairs of mammalian species with large variation in aerobic capacity.

Adaptation, Physiological

Specificity of leg power changes to velocities used in bicycle endurance training.

Increases in leg power production resulting from 8 wk of bicycle endurance training (30 min/day, 5 times/wk) were studied using an isokinetic dynamometer. In addition, biopsies of vastus lateralis were analyzed to characterize muscle ultrastructural changes. Performance increased on the dynamometer specifically near the estimated average knee angular velocity used during the bicycle training (200 degrees/s). Power measurements were made during the first 5 contractions (maximal power: Pmax) and last 5 contractions (final power: Pend) of 25 and 50 consecutive contractions (at 60 and 240 degrees/s, respectively). Pmax and Pend increased only at 240 degrees/s but not at 60 degrees/s. These increases in Pmax (86 W) and Pend (78 W) resulted primarily from longer torque maintenance but also from increased peak torque during each contraction and were close to the increase in mechanical power output maintained on the bicycle (Pb; 78 W) during the training sessions. The specificity of these changes to the angular velocities used in the bicycle training indicates a neural basis to these adaptations. We suggest that these neural adaptations, coupled with the observed enhancement of muscle mitochondrial and capillary density (+41 and +15%, respectively) underlie the increased ability to maintain power production on a bicycle after endurance training.

Adult

Capillarity and mitochondrial distribution in rat myocardium following exercise training.

Rats were subjected to a laddermill running programme either once per week for 6 weeks, or daily for 6 weeks. Heart mass and maximal oxygen consumption rate increased relative to controls and with the frequency of the running programme. Mitochondrial distribution, measured in seven regions within fibres, was similar in all hearts, with a peak volume density of 0.42 +/- 0.01 occurring 4-5 microns from the centre of a capillary. Capillary density decreased with increasing heart mass, but total capillary length and capillary-to-fibre ratio were constant. Thus the higher metabolic demands of the running programmes did not alter the volume density or distribution of mitochondria, despite significant increases in heart mass and decreases in capillarity.

Adenosine Triphosphate

Heat loss from deer mice (Peromyscus): evaluation of seasonal limits to thermoregulation.

This paper investigates the influence of seasonal adaptations to thermoregulatory heat loss for deer mice (Peromyscus) during summer and winter. A general, mechanistic model of heat transfer through fur was evaluated for the structural properties of the fur of deer mice. The model was validated against heat production determined from mice exposed to a range of radiative (wall) temperatures (tr) at air temperatures (ta) of 15, 27 and 34 degrees C. Calculated heat loss from the appendages was subtracted from the measured heat production to yield heat loss from the furred torso. This calculated torso heat loss agreed closely with the predicted fur heat loss for all conditions, as shown by a regression slope near 1 (0.99). Simulations using models of fur and appendage heat loss reveal that the winter increase in thermogenic (heat production) capacity has a greater effect than changes in fur properties in expanding the limits to thermoregulation. Both wind and a clear night sky increase heat loss and can limit thermoregulation to air temperatures above those found in deer mice habitats during winter (-25 degrees C). Thus, despite seasonal adaptations, these simulations indicate that thermoregulation is not possible under certain winter conditions, thereby restricting deer mice to within the protected environment of the leaf litter or snow tunnels.

Acclimatization

Heat loss regulation: role of appendages and torso in the deer mouse and the white rabbit.

Thermal conductance was subdivided into the component conductances of the appendages and torso using a heat transfer analysis for the deer mouse, Peromyscus maniculatus, and the white rabbit, Oryctolagus cuniculus. Our analysis was based on laboratory measurements of skin temperature and respiratory gas exchange made between air temperatures of 8 and 34 degrees C for the deer mouse, and from published data for the white rabbit. Two series conductances to heat transfer for each appendage and torso were evaluated: internal (hin), for blood flow and tissue conduction to the skin surface, and external (hex), for heat loss from the skin surface to the environment. These two series conductances were represented in a single, total conductance (htot). The limit to htot was set by hex and was reached by the torso htot of both animals. The increase in torso htot observed with air temperature for the mouse suggests that a pilomotor change in fur depth occurred. A control of htot below the limit set by hex was achieved by the hin of each appendage. Elevation of mouse thermal conductance (C) resulted from increases in feet, tail, and torso htot. In contrast, the rabbit showed no change in torso htot between 5 and 30 degrees C and ear htot exclusively increased C over these air temperatures. We suggest that the hyperthermia reported for the rabbit at 35 degrees C resulted from C reaching the physical limit set by torso and near hex. Thus the ear alone adjusted rabbit C, whereas the feet, tail, and the torso contributed to the adjustment of mouse C.

Animals

Evaporative water loss: thermoregulatory requirements and measurements in the deer mouse and white rabbit.

Using a physical model of the capacity for non-evaporative heat loss and measurements of metabolic heat production, I evaluated the evaporative requirements for thermoregulation in the deer mouse, Peromyscus maniculatus, and the white rabbit, Oryctolagus cuniculus. The physical limit to non-evaporative heat loss was calculated from the heat transfer properties of the two animals and expressed as a maximum thermal conductance (Cmax). Two physiologically-based thermal conductances were derived from evaporative water loss, respiratory gas exchange and core temperature measurements made between 8 and 34 degrees C on the deer mouse, and taken from published data for the white rabbit. The thermal conductance for non-evaporative heat loss (C) was calculated from net heat production, whereas Cm represented the thermal conductance required to dissipate metabolic heat production. Evaporation is required when metabolic heat production exceeds the capacity for non-evaporative heat loss (as shown by Cm greater than Cmax). However, evaporation increased in both animals although additional capacity to lose heat remained (i.e., C less than Cmax). Evaporation increased with C above 30 degrees C for the mouse and at each 5 degrees C measurement interval from 15 to 30 degrees C for the rabbit. Thus, evaporation was greater than that required for thermoregulation for both animals as determined from a physical model of heat loss because both evaporation and C increased together to regulate heat loss.

Animals

Transfer effects in endurance exercise. Adaptations in trained and untrained muscles.

The effects of 8 weeks of bicycle endurance training (5 X /week for 30 min) on maximal oxygen uptake capacity (VO2max) during arm and leg ergometry, and on the ultrastructure of an untrained arm muscle (m. deltoideus), and a trained leg muscle (m. vastus lateralis) were studied. With the training, leg-VO2max for bicycling increased by +13%, while the capillary per fiber ratio and the volume density of mitochondria in m. vastus lateralis increased by +15% and +40%, respectively. In contrast, the untrained m. deltoideus showed an unchanged capillary per fiber ratio and a decreased mitochondrial volume density (-17%). Despite this decrease of mitochondrial volume arm-VO2max increased by +9%. It seems unlikely that the observed discrepancy can be explained by cardiovascular adaptations, since arm cranking did not fully tax the cardiovascular system (arm-VO2max/leg-VO2max: 0.74 and 0.71 before and after training, respectively). Thus neither cardiovascular adaptations nor local structural changes in the untrained muscles could explain the increased arm-VO2max. However, the enhanced capacity for lactate clearance after endurance training could be sufficient to account for the larger VO2max during arm cranking. We propose that an increased net oxidation of lactate might be responsible for the increased arm-VO2max found after bicycle endurance training.

Adult

Aerobic capacity estimated by exercise vs cold-exposure: endurance training effects in rats.

Two widely used measures of aerobic capacity, the maximal rate of oxygen consumption elicited by exercise (VO2max(ex)) and that induced by cold-exposure (VO2max(cold)), were compared before and after a six-week endurance training period in rats. A laddermill was used to elicit by running VO2max(ex) in a few attempts without training. Endurance training was incremented to achieve 85% of the weekly measured VO2max(ex) during the 25 min/day, 5 days/week sessions. Additional rats were left untrained either as controls or for weekly VO2max(ex) measurement. Mean VO2max(ex) was significantly greater by 34% and 20% (VO2max(ex)Mb, 29% and 9%) in the trained and weekly run groups, respectively, but no differences were found in either VO2max(cold) or body mass. Both training and the measurement of VO2max by exercise were sufficient to elevate VO2max(ex) but the enhancement of cold-exposure VO2 reported by others after endurance training was not apparent in VO2max(cold). Thus, the thermogenically-based VO2max(cold) did not reflect the adaptation to endurance training shown by exercise-elicited VO2max. We conclude that VO2max(ex) and VO2max(cold) cannot be used interchangeably as measures of aerobic capacity.

Animals