Biomedical subjects

W H Martin

Publications and source records attributed to W H Martin.

At least 91 records · Page 5Linked to original sources

PubMed1987

Application of the three-channel lissajous trajectory of auditory brainstem-evoked potentials to the question of generators.

In studies of generators of auditory brainstem-evoked potentials (ABEP), depth recordings and clinical correlates may not reflect all the activity involved. Although the 'inverse problem' is mathematically ill-posed, a synthesis of physico-anatomical data with a three-channel Lissajous trajectory (3CLT) may indicate the actual number and identity of generators. A 3CLT of ABEP in three-dimensional voltage space, is isomorphic with the vector tip representing the momentary centrally located dipole in a uniform, spherical volume conductor. This isomorphism enables approximations of ABEP dipole equivalents to be made. 3CLT summarizes the surface activity in a single plot. It accentuates correlations within the orthogonal records, such as planarity of segments, allowing segmentation of the analysis epoch into components. These properties of 3CLT simplify the analysis of parametric effects on the surface distribution of ABEP components. The results of applying this technique indicate the experimental conditions under which the assumptions for the approximation of generators are closest to being fulfilled. Of all the points along the trajectory, apices (points with maximum absolute amplitude and curvature) have the most unique generators. The 3CLT to low-intensity and high-rate clicks, indicate more unique generators than the customarily used high-intensity slow-rate clicks, in which considerable temporal overlap of generator activity exists.

Brain Stem↗

PubMed1986

Kinetics of inhibition and binding of dicyclohexylcarbodiimide to the 82,000-dalton mitochondrial K+/H+ antiporter.

Inhibition of K+/H+ antiport by N,N'-dicyclohexylcarbodiimide in Mg2+ depleted mitochondria follows first order kinetics, exhibiting a half-time of 13 min when mitochondria are incubated with 50 nmol/mg inhibitor at 0 degrees C. 14C radiolabeled N,N'-dicyclohexylcarbodiimide binds to the 82,000-dalton protein, and the second order rate constant for binding is found to be approximately the same as the second order rate constant for inhibition. These findings provide additional confirmation of the identification of this porter with the 82,000-dalton protein and permit us to estimate that rat liver mitochondria contain about 8 pmol/mg of K+/H+ antiporter with a turnover number of 700 s-1. The K+/H+ antiporter of rat liver mitochondria is protected from N,N'-dicyclohexylcarbodiimide inhibition and binding by quinine and by endogenous Mg2+. An 82,000-dalton, [14C]N,N'-dicyclohexylcarbodiimide-binding protein is also observed in rat liver submitochondrial particles, establishing this as an integral protein of the inner membrane. Submitochondrial particles, presumed to be inverted in membrane orientation, are protected from radiolabeling by external Mg2+, supporting the contention that the Mg2+ binding site is localized to the matrix side of the K+/H+ antiporter.

Animals↗

PubMed1986

On the mechanism by which dicyclohexylcarbodiimide and quinine inhibit K+ transport in rat liver mitochondria.

Passive uptake of potassium acetate into the mitochondrial matrix can be induced by nigericin, a K+/H+ antiporter, or by A23187, a Mg2+/2H+ antiporter. The latter process is thought to reflect operation of the Mg2+-dependent, endogenous K+/H+ antiporter, but there is ambiguity with respect to the mechanism of K+ transport in this assay (Nakashima, R.A., and Garlid, K.D. (1982) J. Biol. Chem. 257, 9252-9254). Kinetic analysis of potassium acetate transport provides verification that Mg2+ depletion 1) unmasks the K+/H+ antiporter, 2) opens up an intrinsic anion uniporter, 3) has no effect on acetic acid transport, and 4) does not induce high K+ uniport conductance. Mg2+-dependent uptake of potassium acetate is thereby shown to be mediated specifically by operation of the endogenous K+/H+ antiporter, as previously proposed. An extension of this analysis confirms that N,N'-dicyclohexylcarbodiimide and quinine block potassium acetate uptake via specific action on the K+/H+ antiporter. These findings support those of a previous study (Martin, W.H., Beavis, A.D., and Garlid, K.D. (1984) J. Biol. Chem. 259, 2062-2065) in which binding of [14C]N,N'-dicyclohexylcarbodiimide to membrane proteins under selective conditions was used to identify an 82,000-dalton band as the protein responsible for K+/H+ antiport in mitochondria.

Acetates↗

PubMed1986

Three-channel Lissajous' trajectory of human auditory brain-stem evoked potentials. II. Effects of click intensity.

Three-channel Lissajous' trajectories (3-CLT) of the human auditory brain-stem evoked potentials (ABEP) were recorded from 14 adult subjects at 15, 45, and 75 dB (nHL). The 3-CLTs were analysed and described in terms of their constituent planar segments and their trajectory amplitudes at each stimulus level. At 75 dB, 9 planar segments were observed, each having unique apex latency, boundaries, duration, shape, size and orientation in voltage space. As stimulus levels were lowered, changes were noted in apex latency and trajectory amplitude which parallelled changes seen under similar experimental conditions using single-channel ABEP. In addition, changes were seen in planar segment number, boundaries, duration, shape, size and orientation, all of which could be related to decreased generator activity. It is proposed that at high stimulus levels, there is significant temporal overlap of generator activity which results in a larger number of planar segments and single-channel peaks than at low stimulus levels. This may be important to the identification of the specific generators of the ABEP and their appropriate clinical usage.

Brain Stem↗

PubMed1986

Three-channel Lissajous' trajectory of human auditory brain-stem evoked potentials. III. Effects of click rate.

Three-channel Lissajous' trajectories (3-CLT) of the human auditory brain-stem evoked potentials (ABEPs) were recorded from 14 adult subjects using click rates of 10, 55 and 80/sec. The 3-CLTs were analysed and described in terms of their constituent planar segments and their trajectory amplitudes at each stimulus rate. Increasing stimulus rate resulted in an increase of planar segment duration which was more pronounced for segments 'a' and 'e', an increase in apex latency which was more pronounced the later the component and a decrease in planar segment size and peak trajectory amplitude which was more pronounced the earlier the component. These findings support the involvement of synaptic efficacy changes in the effects of stimulus rate on ABEP. The results are explained by overlapping convergence and divergence in the ascending auditory pathway. These results support the notion that the principal generator of each component is activated by the principal generator of the previous component, with some temporal overlap of their activities. Such temporal overlap may be minimized by using low intensity high rate stimuli.

Brain Stem↗

PubMed1986

Effects of physical deconditioning after intense endurance training on left ventricular dimensions and stroke volume.

To determine the role of preload in maintaining the enhanced stroke volume of upright exercise-trained endurance athletes after deconditioning, six highly trained subjects undergoing upright and supine bicycle ergometry were characterized before and after 3, 8 and 12 weeks of inactivity that reduced oxygen uptake by 20%. During exercise, oxygen uptake, cardiac output by carbon dioxide rebreathing, cardiac dimensions by M-mode echocardiography, indirect arterial blood pressure and heart rate were studied simultaneously. Two months of inactivity resulted in a reduction in stroke volume, calculated as cardiac output/heart rate, during upright exercise (p less than 0.005) without a significant change during supine exercise. A concomitant decrease in the left ventricular end-diastolic dimension from the trained to the deconditioned state was observed in the upright posture (5.1 +/- 0.3 versus 4.6 +/- 0.3 cm; p = 0.02) but not with recumbency (5.4 +/- 0.2 versus 5.1 +/- 0.3 cm; p = NS). There was a strong correlation between left ventricular end-diastolic dimension and stroke volume (r greater than 0.80) in all subjects. No significant changes in percent fractional shortening or left ventricular end-systolic dimension occurred in either position after cessation of training. Estimated left ventricular mass was 20% lower after 3 and 8 weeks of inactivity than when the subjects were conditioned (p less than 0.05 for both). Thus, the endurance-trained state for upright exercise is associated with a greater stroke volume during upright exercise because of augmented preload. Despite many years of intense training, inactivity for only a few weeks results in loss of this adaptation in conjunction with regression of left ventricular hypertrophy.

Adult↗

PubMed1986

Comparison of glare in YAG-damaged intraocular lenses: injection-molded versus lathe-cut.

A comparative analysis of YAG laser intraocular lens (IOL) damage was undertaken on injection-molded and lathe-cut IOLs. Damage sites were evaluated with polarized light. A consistent positive polarization was observed in the damage sites of lathe-cut IOLs. A consistent negative polarization was observed in the damage sites of injection-molded IOLs. The presence of positive polarization in IOL damage sites may be correlated with increased potential for glare. Results and clinical implications are discussed.

Equipment Design↗

PubMed1986

Muscle triglyceride utilization during exercise: effect of training.

The respiratory exchange ratio (RER) is lower during exercise of the same intensity in the trained compared with the untrained state, even though plasma free fatty acids (FFA) and glycerol levels are lower, suggesting reduced availability of plasma FFA. In this context, we evaluated the possibility that lipolysis of muscle triglycerides might be higher in the trained state. Nine adult male subjects performed a prolonged bout of exercise of the same absolute intensity before and after adapting to a strenuous 12-wk program of endurance exercise. The exercise test required 64% of maximum O2 uptake before training. Plasma FFA and glycerol concentrations and RER during the exercise test were lower in the trained than in the untrained state. The proportion of the caloric expenditure derived from fat, calculated from the RER, during the exercise test increased from 35% before training to 57% after training. Muscle glycogen utilization was 41% lower, whereas the decrease in quadriceps muscle triglyceride concentration was roughly twice as great (12.7 +/- 5.5 vs. 26.1 +/- 9.3 mmol/kg dry wt, P less than 0.001) in the trained state. These results suggest that the greater utilization of FFA in the trained state is fueled by increased lipolysis of muscle triglyceride.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1985

Three-channel Lissajous' trajectory of human auditory brain-stem evoked potentials. I. Normative measures.

Three-channel Lissajous' trajectories (3-CLTs) of auditory brainstem evoked potentials (ABEPs) were obtained from 14 humans (28 ears) in response to 75 dB nHL, 10/sec alternating polarity clicks. A normative set of 3-CLT quantitative measures was calculated and compared with amplitudes and latencies of the simultaneously recorded, single-channel, vertex-mastoid ABEP. The comparison included average values as well as intersubject variability. The 3-CLT measures included: apex latencies; planar segment durations, orientation, size and shape; trajectory-amplitude peaks and their latencies. Apex latencies of 3-CLT were comparable to peak latencies of the vertex-mastoid records, both in absolute values and in intersubject variability. Durations of planar segments were approximately 0.7 msec and their standard deviations were about a half of their average. Individual planar segment orientations were typically within 50 degrees of the normative average. Trajectory amplitudes were, in general, somewhat larger than peak amplitudes of the vertex-mastoid records, while their intersubject variabilities were comparable. Size and shape measures of planar segments were variable across subjects, making their clinical use, in their present form, questionable. The quantitative study of the 3-CLT of auditory brain-stem evoked potentials will enable evaluation of normal, as well as pathological, evoked potentials, to further the understanding and utility of this comprehensive representation of brain-stem function.

Adult↗

PubMed1985

Effects of detraining on responses to submaximal exercise.

Seven endurance-trained subjects were studied 12, 21, 56, and 84 days after cessation of training. Heart rate, ventilation, respiratory exchange ratio, and blood lactate concentration during submaximal exercise of the same absolute intensity increased (P less than 0.05) progressively during the first 56 days of detraining, after which a stabilization occurred. These changes paralleled a 40% decline (P less than 0.001) in mitochondrial enzyme activity levels and a 21% increase in total lactate dehydrogenase (LDH) activity (P less than 0.05) in trained skeletal muscle. After 84 days of detraining, the experimental subjects' muscle mitochondrial enzyme levels were still 50% above, and LDH activity was 22% below, sedentary control levels. The blood lactate threshold of the detrained subjects occurred at higher absolute and relative (i.e., 75 +/- 2% vs. 62 +/- 3% of maximal O2 uptake) exercise intensities in the subjects after 84 days of detraining than in untrained controls (P less than 0.05). Thus it appears that a portion of the adaptation to prolonged and intense endurance training that is responsible for the higher lactate threshold in the trained state persists for a long time (greater than 85 days) after training is stopped.

Blood Glucose↗

PubMed1984

Cardiovascular sensitivity to epinephrine in the trained and untrained states.

Heart rate (HR), blood pressure (BP) and inotropic responses to acute exercise are partially mediated by sympathetic stimulation. Physical conditioning reduces exercise HR and improves maximal stroke volume and cardiac output. Uncertainty exists regarding the role of altered catecholamine sensitivity in producing these changes in man. In 6 highly trained men, noninvasive methods were used to serially assess the effect of cessation of training on the resting HR, BP and left ventricular contractile function in response to constant epinephrine infusion. Plasma epinephrine concentration during infusion did not vary with inactivity and was similar to that attained with strenuous exercise. Two subjects showed an increase in chronotropic sensitivity to epinephrine and 4 showed no consistent change. Despite a significant decline in exercise capacity and no apparent change in cardiac loading conditions, there was no persistent effect of inactivity on BP or left ventricular function as assessed by echocardiography and systolic time intervals. Therefore, an alteration in sensitivity to epinephrine is unlikely to account for the hemodynamic adaptations to endurance exercise training in healthy men.

Adaptation, Physiological↗

PubMed1984

Identification of an 82,000-dalton protein responsible for K+/H+ antiport in rat liver mitochondria.

Under highly selective conditions, pretreatment of rat liver mitochondria with N,N'-dicyclohexylcarbodiimide (DCCD) results in 95% inhibition of K+/H+ antiport. This inhibition is irreversible. The K+/H+ antiporter is reversibly inhibited by physiological (Mg2+ and H+) and pharmacological (quinine and propranolol) inhibitors. Each of these inhibitors protects the K+/H+ antiporter against inhibition by DCCD. DCCD is without effect on Na+/H+ antiport under all conditions tested, confirming our contention that rat liver mitochondria possess two different alkali cation/proton antiporters (Nakashima, R. A., and Garlid, K. D. (1982) J. Biol. Chem. 257, 9252-9254). The selective nature of irreversible inhibition by DCCD has enabled us to label and identify the protein responsible for K+/H+ antiport. This protein, the first cation antiporter so identified, migrates on sodium dodecyl sulfate-polyacrylamide gels with a molecular weight of 82,000.

Animals↗

PubMed1984

Effect of prolonged intense endurance training on systolic time intervals in patients with coronary artery disease.

We studied the effect of exercise training (ET) on systolic time intervals (STI) in 13 patients with coronary artery disease (CAD). All patients trained for at least 10 months. They exercised three times/week at 50% to 70% of maximal oxygen uptake (VO2max) for the initial 3 months and at least four times/week for approximately 50 minutes at 70% to 90% of VO2max thereafter. A significant training effect was documented by an increase in VO2max from 26.0 +/- 4.3 to 37.2 +/- 5.8 ml/kg/min (p less than 0.01), a lower heart rate (HR) at rest, and a lower blood pressure and HR during submaximal work. The indices of total electromechanical systole (QS2I) and left ventricular ejection time (LVETI) did not change. However, pre-ejection period index (PEPI) decreased from 137 +/- 9 msec to 129 +/- 9 msec (p less than 0.01). PEP/LVET decreased from 0.373 +/- 0.028 to 0.342 +/- 0.032 (p less than 0.01). Left ventricular end-diastolic dimension and posterior wall thickness, measured echocardiographically, were increased after training. We conclude that exercise training may improve myocardial performance in some patients with CAD.

Adult↗

PubMed1984

Effects of stopping exercise training on epinephrine-induced lipolysis in humans.

It has been reported that in rats endurance exercise training enhances the sensitivity of adipose tissue to the lipolytic action of catecholamines. The purpose of this study was to determine whether endurance training has a similar effect on the lipolytic response to epinephrine in humans. Four days after cessation of training, a constant infusion of epinephrine resulted in a significantly smaller increase in serum free fatty acids (0.57 +/- 0.40 vs. 1.06 +/- 0.30 mM; P less than 0.01) and blood glycerol (0.07 +/- 0.01 vs. 0.12 +/- 0.03 mM; P less than 0.01) and a greater rise in blood lactate (1.24 +/- 0.51 vs. 0.69 +/- 0.44 mM; P less than 0.01) above preinfusion levels than when the subjects were training. No further change in these responses occurred after 2 mo of inactivity. Plasma glucose and glucagon responses to epinephrine remained constant throughout the study. Plasma insulin concentrations before and during epinephrine infusion were higher than in the trained state only after 2 mo of inactivity. These findings suggest that epinephrine-induced lipolysis is enhanced in endurance-exercise-trained individuals but that this adaptation is lost very rapidly after cessation of exercise.

Adipose Tissue↗

PubMed1984

Effects of intense exercise training on plasma catecholamines in coronary patients.

This paper reports the effect of 12 mo of intense endurance exercise training on the plasma catecholamine response to exercise in 11 male patients [aged 50 +/- 8 yr (mean +/- SD)] with coronary artery disease. A substantial adaptation to training was attained as evidenced by a 42% increase in maximum O2 uptake capacity. At rest, heart rate was lower after training, but resting blood pressure and plasma catecholamines were unchanged. At the same absolute work rate, plasma norepinephrine and epinephrine levels, rate pressure product, and ischemic S-T segment depression were all significantly lower after training. A higher plasma norepinephrine level was attained at maximal exercise after training (2,049 +/- 654 before vs. 3,408 +/- 1,454 pg/ml after, P less than 0.025); this was associated with a higher systolic blood pressure (175 +/- 25 before vs. 188 +/- 22 mmHg after, P less than 0.025) and a higher rate-pressure product (25.3 X 10(3) +/- 4.5 X 10(3) before vs. 27.6 X 10(3) +/- 5.2 X 10(3) after, P less than 0.025). Despite the higher plasma norepinephrine level and rate pressure product, S-T segment depression at maximal exercise was unchanged. These findings suggest that some patients with coronary arterial disease can attain a higher myocardial O2 requirement, without electrocardiographic evidence of increased ischemia, after prolonged strenuous exercise training.

Adaptation, Physiological↗

PubMed1984

Time course of loss of adaptations after stopping prolonged intense endurance training.

Seven endurance exercise-trained subjects were studied 12, 21, 56, and 84 days after cessation of training. Maximal O2 uptake (VO2 max) declined 7% (P less than 0.05) during the first 21 days of inactivity and stabilized after 56 days at a level 16% (P less than 0.05) below the initial trained value. After 84 days of detraining the experimental subjects still had a higher VO2 max than did eight sedentary control subjects who had never trained (50.8 vs. 43.3 ml X kg-1 X min-1), due primarily to a larger arterial-mixed venous O2 (a-vO2) difference. Stroke volume (SV) during exercise was high initially and declined during the early detraining period to a level not different from control. Skeletal muscle capillarization did not decline with inactivity and remained 50% above (P less than 0.05) sedentary control. Citrate synthase and succinate dehydrogenase activities in muscle declined with a half-time of 12 days and stabilized at levels 50% above sedentary control (P less than 0.05). The initial decline in VO2 max was related to a reduced SV and the later decline to a reduced a-vO2 difference. Muscle capillarization and oxidative enzyme activity remained above sedentary levels and this may help explain why a-vO2 difference and VO2 max after 84 days of detraining were still higher than in untrained subjects.

Adaptation, Physiological↗

PubMed1983

Effects of detraining on enzymes of energy metabolism in individual human muscle fibers.

Muscle biopsies were obtained from three cyclists and four runners at the end of 10-24 mo of intensive training and after intervals of detraining up to 12 wk. Control samples came from four untrained persons and four former athletes. Macro mixed fiber samples were assayed for lactate dehydrogenase, adenylate kinase, glycogen phosphorylase, citrate synthase, malate dehydrogenase, beta-hydroxyacyl-CoA dehydrogenase, succinate dehydrogenase, beta-hydroxybutyrate dehydrogenase, creatine kinase, hexokinase, 1-phosphofructokinase, fructosebisphosphatase, protein, and total creatine. In the case of three trained persons and two controls, the first six of the enzymes were also measured in individual fibers. Before detraining, enzymes of oxidative metabolism were substantially higher than in controls, and differences in levels between type I and type II fibers were smaller. During detraining, oxidative enzymes were decreased in both fiber types but the type II fibers did not fall to control levels even after 12 wk. Phosphorylase increased with detraining in both fiber types. The same is true for lactate dehydrogenase and adenylate kinase, except in the case of the type I fibers of one individual. Among the other six enzymes (measured in mixed fiber samples), only hexokinase was consistently affected (decreased) by detraining.

Adenylate Kinase↗

PubMed1983

Blood lactate threshold in some well-trained ischemic heart disease patients.

Six patients with ischemic heart disease who had exercised intensely for longer than 1 yr appeared to have a disproportionately high capacity for endurance exercise relative to VO2 max. They were compared with healthy runners of the same age (mean 55 yr) with similar training programs (6-12 km/day, 5 day/wk). The trained patients had a significantly (P less than 0.05) lower maximal cardiac output (-17%) and VO2 max (-18%, 37 vs. 45 ml . kg-1 . min-1). Despite their lower VO2 max, the trained patients were able to run 8 km at the same speed as the normal runners (approximately 189 m/min). The trained patients' ability to keep pace with the normal subjects was apparently due to a very high lactate threshold (LT) relative to VO2 max. The patients' LT (lactate 1 mM above base line) occurred at a treadmill running speed of 176 m/min, which elicited 100% of their VO2 max, compared with a LT at 178 m/min and 84% of VO2 max in the normal subjects (P less than 0.01). Our results show that some individuals with VO2 max limited by impaired cardiac function can undergo adaptations to training that enable them to maintain close to a metabolic steady state during exercise that elicits VO2 max.

Aged↗