Biomedical subjects

D M O'Drobinak

Publications and source records attributed to D M O'Drobinak.

9 recordsLinked to original sources

PubMed1996

Decreases in steady-state muscle performance and vessel density in reduced renal mass hypertensive rats.

In this study we hypothesized that reduced renal mass (RRM) hypertension, which is associated with a chronic reduction in vessel density, could reduce steady-state muscle performance. Vessel density and isometric tetanic force from the in situ gastrocnemius-plantaris-soleus muscle group were studied in age-matched normotensive sham-operated control (HSS) and hypertensive RRM rats on a high-salt (4.0% NaCl) diet (HSRRM) and a low-salt (0.4% NaCl) diet (LSS and LSRRM, respectively). The Achilles tendon was isolated and connected to a force transducer. Peak isometric tension elicited by sciatic nerve stimulation (1/s for 10 min, 50 impulses/s for 330 ms) was not different between the groups. In the LSS, HSS, and LSRRM groups, tension decreased similarly at 3 min to 375 +/- 22, 447 +/- 26, and 424 +/- 21 g/g, respectively. Tension was significantly reduced in the HSRRM group (203 +/- 45 g/g) relative to the LSS, HSS, and LSRRM groups by 3 min. These differences in steady-state tension persisted throughout the remainder of the experiment. Microvessel density, measured by the lectin fluorescence technique, was reduced significantly only in the soleus, plantaris, and medial gastrocnemius of the HSRRM rats. We conclude that RRM hypertension results in reductions in vessel density (rarefaction) that are associated with decreased steady-state muscle performance.

Animals↗

PubMed1995

A computerized method for determination of microvascular density.

Currently accepted stereological methods for vascular density measurements involve manual counting of labeled vessels with a grid image overlay and determination of vessel-grid intersections. This method both is tedious and may be prone to error; therefore, our laboratory has developed a method for computer-automated determination of microvascular density using digital image processing techniques. An image of the microvasculature is acquired using computer videomicroscopy. The image is processed in three general steps, involving (1) background correction, (2) thresholding of the gray level image to create a binary image, and (3) processing of the binary image using erosion, dilation, and skeletonization algorithms. Testing of this procedure was performed on 328 typical images of skeletal muscle tissue sections taken from the hindlimb of Sprague-Dawley rats and quantitated by both traditional measures and our new computer method. Results from this comparison reveal that the automated vessel counting is highly correlated (r2 = 0.71) and decreased analysis time from 15 min/image to 30 sec/image when compared with manual counting methods. Our computer-based method also appears to be superior to the traditional method due to the unbiased and nonsubjective nature of determining vessel-grid intersections.

Animals↗

PubMed1994

Metabolic and work capacity of skeletal muscle of PFK-deficient dogs studied in situ.

Mechanical and metabolic relationships of muscle lacking phosphofructokinase (PFKD) activity were compared with muscle having normal phosphofructokinase (NORM) activity by using the gastrocnemius-plantaris muscle group with isolated circulation in situ. Muscle contractile properties were similar in both groups. Initial power output (W) during repetitive tetanic (200 ms, 50 impulses/s) isotonic contractions was similar in both groups; however, W declined significantly more (30-80%) in PFKD than in NORM muscle over time, with a constant O2 uptake (VO2)/W. Despite similar O2 and substrate delivery, PFKD muscle had a lower VO2 (42-55%), less glucose uptake, similar free fatty acid uptake, and lactic acid uptake rather than output, during contractions. Muscle venous H+ concentration, strong ion difference, and PCO2 increased during contractions, the magnitude of change being smaller in PFKD muscle. Elevating arterial lactate concentration before contractions in PFKD muscle resulted in significant improvements in W and VO2 without altering the acid-base exchange at the muscle. Increasing O2 delivery by increasing arterial O2 concentration in PFKD dogs did not improve W or VO2. We conclude that, despite no inherent mechanical or contractile differences, PFKD muscle has a severely limited oxidative capacity and exaggerated fatigue and blood flow responses to contractions due to limited substrate metabolism resulting from the inability to utilize glycogen and/or glucose.

Acid-Base Equilibrium↗

PubMed1991

Fatigue of mammalian skeletal muscle in situ during repetitive contractions.

When the gastrocnemius-plantaris muscle group of the dog is stimulated to contract repetitively for 30 min at frequencies high enough to generate VO2 levels at or near VO2 max, VO2 and mechanical performance decline with time. This decline with time is fatigue, and it occurs during twitch and tetanic contractions that are isometric or isotonic. There is oxidation of the mitochondrial electron transport system, and net lactic acid output is transient, ending after 20 min of contractions. Energy and substrate stores and intracellular pH are only moderately changed and do not appear to be well correlated with the development of fatigue. Blood flow through the muscle is well correlated with the development of fatigue and decreases as fatigue develops in a manner that keeps the blood arteriovenous O2 difference nearly constant. Changing the blood flow alters the rate of development of fatigue as an inverse relation, and this response does not appear to be related to changes in the availability of O2 in the mitochondria. Nerve-muscle transmission of excitation does not seem to be involved in the development of fatigue. Excitation-contraction coupling is well accepted to be at least part of the genesis of the development of fatigue. Metabolic limitations and control may affect excitation-contraction coupling by one or more changes in the internal environment. Blood flow affects this system by an unknown mechanism. The role of blood flow in fatigue deserves further consideration.

Animals↗

PubMed1991

Differences between VO2 maxima of twitch and tetanic contractions are related to blood flow.

The purpose of this investigation was to compare oxygen uptake (VO2) and fatigue characteristics of isotonic tetanic contractions with those observed during isotonic twitches in dog gastrocnemius-plantaris muscle. Tetanic contractions (1/s, 200-ms trains of 50 impulses/s) elicited a peak VO2 of 9.01 +/- 0.42 mumol.g-1.min-1, which declined 29% in 30 min. The peak was significantly lower during 4/s twitches (6.23 +/- 0.36 mumol.g-1.min-1), but the rate of decline was similar. Peak blood flow (Q) was 37% higher and decreased more slowly during tetanic than twitch contractions. VO2/Q and VO2/venous PO2 were similar in both groups at peak VO2 and later declined or remained constant over time. Power was significantly greater with tetanic contractions with the relative decline between 3 and 30 min similar in both groups (32 and 37%). In conclusion, tetanic contractions result in significantly higher VO2 and power than do twitch contractions. This was derived primarily from increased Q because the arteriovenous O2 difference was similar. A significant determinant of the difference in Q between twitch and tetanic contractions is mechanical hindrance of Q. There is relatively more time for unhindered flow in the tetanic contractions. In electrically stimulated muscles, maximal VO2 is related to Q and reflects mainly Q through the muscle rather than the VO2 capacity of the muscle.

Animals↗

PubMed1991

Regulation of muscle lactate production.

It is not possible to make accurate measurements of muscle lactic acid net exchange during exercise by application of the Fick relationship. To make accurate measurements of lactic acid net exchange, preparations with isolated circulations have been used. Since such preparations utilize relatively small muscles or groups of muscles, the data apply to muscle contractions, not exercise. In exercise, external influences may affect lactate exchange. The net lactic acid exchange (L) of the isolated dog gastrocnemius-plantaris muscle group has been quantified for repetitive twitch and tetanic contractions, progressive contractions, and four repetitions of 30-s intense contractions with 3.5 min of recovery between each. Epinephrine has been infused during repetitive and progressive contractions; modest ischemia and hypoxic hypoxia, and the oxidation-reduction state of mitochondrial cytochrome a-a3 have been investigated. After the initiation of repetitive contractions, L rises transiently to a peak at 3-5 min and then declines to net uptake after 30 min of contractions. The peak L is roughly proportional to VO2. L rises progressively during progressive contractions to levels lower than the peak in repetitive contractions. Epinephrine increases L transiently during repetitive contractions and increases L during progressive contractions. L rises to levels similar to the repetitive peak during the four repeated 30-s bouts. Cytochrome a-a3 was more oxidized during contractions than when at rest. Ischemia has little or no effect on L. Hypoxic hypoxia sufficient to produce hypoxidosis increased L sharply, but transiently. Muscle L reflects the balance between the production of the products of glycolysis and their removal into the mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effects of ischemic and hypoxic hypoxia on VO2 and lactic acid output during tetanic contractions.

We measured O2 uptake (VO2), CO2 output (VCO2), and net lactic acid output (L) during a 30-min period of repetitive 1/s isotonic tetanic contractions of the dog gastrocnemius-plantaris muscle group. The conditions were modest ischemic hypoxia (ischemia), hypoxia hypoxia (hypoxia), and free-flow normoxia (control). The major goal was to assess the effects of these perturbations on L during contractions. Ischemia and hypoxia were initiated just before the start of the contractions and at minute 7 of contractions in separate groups of experiments. Whenever applied, both ischemia and hypoxia reduced VO2 compared with the control values. When ischemia was initiated at the start of contractions, L was reduced transiently compared with the controls. When ischemia began at minute 7, L was increased modestly but transiently compared with the controls. When hypoxia was initiated at the start of contractions, L was increased during the entire period of contractions. The L pattern was the same as in the controls, rising to a maximal value at 3 min and declining steadily to a lower value at 30 min. When hypoxia began at minute 7, L declined initially at a slower rate than it did in the controls and was thereby elevated above the controls from 9 to 30 min. Ischemia was associated with a more rapid reduction in mechanical performance than hypoxia. The data suggest that the mechanisms of the decreased mechanical performance and VO2 are different for ischemia and hypoxia.

Animals↗

PubMed1989

Oxidation/reduction state of cytochrome oxidase during repetitive contractions.

There is disagreement regarding whether inadequate O2 determines maximal O2 uptake (VO2max) and lactic acid output (L) during muscular activity. Direct assessment of mitochondrial cytochrome oxidase (cytochrome a-a3) oxidation/reduction (O/R) state should provide an unequivocal answer for this issue. A new near-infrared spectrophotometric method was used to measure the O/R state of cytochrome a-a3 of dog gastrocnemius-plantaris muscle in situ during repetitive isotonic twitch and tetanic contractions. Three contraction frequencies were used for each contraction type in alternating sequence to provide a wide range of VO2 up to VO2max. VO2 and L were measured after 3 and 9 min of a 10-min contraction period, and 15 min were allowed for recovery between contraction periods. VO2 increased with contraction frequency. L was variably increased with contraction frequency at 3 min and uptake usually occurred at 9 min, except at the highest tetanic frequency. The O/R span of cytochrome a-a3 was determined by respiring the animals with 100% N2 to determine the most reduced state. This was followed by respiration with 100% O2, which gave the most oxidized state transiently during recovery. Within this span in muscles at rest, cytochrome a-a3 was 50-80% oxidized. During contractions of both types at all frequencies, cytochrome a-a3 always became more oxidized by an additional 10-20%. These findings should put to rest any arguments that inadequate O2 is a determinant of VO2max or L under the conditions of these experiments: repetitive contractions with free flow in self-perfused muscles and normoxia.

Animals↗

PubMedDate not supplied

Mathematical analysis of type-I and type-IIb muscle fiber force generation in renal hypertension.

Previous results from our laboratory have shown that isometric tension development is significantly lower in reduced renal mass (RRM) hypertensive rats when compared to sham-operated controls. The current study was designed to mathematically analyze isometric tetanic contraction profiles and determine the relative contribution of fast-glycolytic (FG) and slow-oxidative (SO) muscle fibers produced by the isolated gastrocnemius-plantaris-soleus muscle group of RRM and sham rats. Because renal hypertension has been shown to be associated with a reduction in microvascular density, we hypothesized that renal hypertension leads to a decrease in SO muscle fiber contribution to force generation. The mathematical model determined the force contribution of two independent muscle fiber components, SO and FG, to the contraction and relaxation phase of isometric tetanic contractions. Each phase was modeled as having an exponentially rising contraction phase during the stimulus period and an exponentially decaying relaxation phase when the stimulus was removed. Each fiber type's tension was also scaled by an envelope function describing the fatigue over the contraction bout. The model, which included 10 parameters, was fit to experimental data by using a nonlinear optimization method and described certain limited characteristics of both fiber types. Results from this model suggest that renal hypertension affects skeletal muscle force generation primarily by decreasing the SO muscle fiber contribution to the total developed tension, decreasing performance and increasing muscle fatigue in RRM rats.

Animals↗