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Biomedical subjects

W R Hiatt

Publications and source records attributed to W R Hiatt.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effect of intravenous L-carnitine on carnitine homeostasis and fuel metabolism during exercise in humans.

This study was undertaken to challenge the hypothesis that short-term administration of carnitine during exercise can modify skeletal muscle carnitine homeostasis and fuel metabolism in normal humans. With a randomized, blinded, crossover design, subjects received carnitine or placebo at the start of a bicycle ergometer exercise session. During the 2 hours after intravenous administration of 185 mumol/kg carnitine, carnitine kinetics could be described with a central compartment volume of distribution of 200 ml/kg, a total clearance from this compartment of 1.9 ml/min/kg, and a renal clearance of 1.3 ml/min/kg. Carnitine administration had no effect on muscle total carnitine content or the workload-dependent accumulation of acylcarnitines in skeletal muscle. Carnitine had no effect on the respiratory exchange ratio, muscle lactate accumulation, plasma lactate concentration, muscle glycogen utilization, or plasma beta-hydroxybutyrate concentration during exercise. Thus the skeletal muscle carnitine pool is segregated from dramatic changes in the plasma carnitine pool, and short-term administration of carnitine has no significant effect on fuel metabolism during exercise in humans.

Adult↗
PubMed1994

Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response.

BACKGROUND: In patients with intermittent claudication, a supervised walking exercise program increases peak exercise performance and community-based functional status. Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment. However, the potential benefits of training modalities other than walking exercise, such as strength training, have not been critically evaluated in this patient population. The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance. METHODS AND RESULTS: Twenty-nine patients with disabling claudication were randomized to 12 weeks of supervised walking exercise on a treadmill (3 h/wk at a work intensity sufficient to produce claudication), strength training (3 h/wk of resistive training of five muscle groups of each leg), or a nonexercising control group. Graded treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance. After 12 weeks, patients in the treadmill training program had a 74 +/- 58% increase in peak walking time as well as improvements in peak oxygen consumption (VO2) and the onset of claudication pain. Patients in the strength-trained group had a 36 +/- 48% increase in peak walking time but no change in peak VO2 or claudication onset time. Control subjects had no changes in any of these measures over the 12-week period. After the first 12 weeks, patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training. This resulted in an additional 49 +/- 53% increase in peak walking time (total of 128 +/- 99% increase over the 24 weeks). After the initial 12 weeks, patients in the strength-trained group began 12 weeks of supervised treadmill training, and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise. The combined strength and treadmill training program and treadmill training after 12 weeks of strength training resulted in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone. CONCLUSIONS: A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication, with continued improvement over 24 weeks of training. In contrast, 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise. Finally, strength training, whether sequential or concomitant, did not augment the response to a walking exercise program.

Aged↗
PubMed1993

Simultaneous inhibition of two tomato fruit cell wall hydrolases, pectinmethylesterase and polygalacturonase, with antisense gene constructs.

The cloning and sequencing of two cDNAs representing pectinmethylesterase (PME) RNAs from tomato fruit is reported. The clones were used to construct chimeric antisense PME genes designed for high-level constitutive expression in plants. A full-length antisense PME gene construct, in conjunction with a chimeric antisense polygalacturonase gene, was introduced into tomato plants via Agrobacterium-mediated transformation. Simultaneous and significant reduction in the mRNA and protein levels of these normally highly abundant cell wall hydrolases of the pectin degradation pathway were observed in ripe fruit of transformants. Thus, antisense gene constructs in plants can be used to block multiple steps in metabolic pathways simultaneously.

Amino Acid Sequence↗
PubMed1993

Chronic changes in skeletal muscle histology and function in peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is associated with an impairment in exercise performance and muscle function that is not fully explained by the reduced leg blood flow during exercise. This study characterized the effects of PAD on muscle function, histology, and metabolism. METHODS AND RESULTS: Twenty-six patients with PAD and six age-matched control subjects were studied. Ten of the PAD patients had unilateral disease, which permitted paired comparisons between their diseased and nonsymptomatic legs. All PAD patients had a lower peak treadmill walking time and peak oxygen consumption than controls. Vascular disease (diseased leg in unilateral patients and the most severely diseased leg in bilateral patients) was associated with decreased calf muscle strength compared with control values. In patients with unilateral disease, the diseased legs had a greater percentage of angular fibers (indicating chronic denervation) and a decreased type II fiber cross-sectional area (expressed as percent of total fiber area) compared with the nonsymptomatic, or control, legs. In diseased legs, gastrocnemius muscle strength was correlated with the total calf cross-sectional area (r = 0.78, p < 0.05) and type II fiber cross-sectional area (r = 0.63, p < 0.05). Activities of citrate synthase, phosphofructokinase, and lactate dehydrogenase in all 26 PAD patients (most diseased leg) did not differ from control values. Despite a wide range in citrate synthase activity in PAD patients, activity of this enzyme was not correlated with muscle strength or treadmill exercise performance. CONCLUSIONS: In patients with PAD, gastrocnemius muscle weakness is associated with muscle fiber denervation and a decreased type II fiber cross-sectional area. In contrast, the PAD patients displayed substantial heterogeneity in muscle enzyme activities that was not associated with exercise performance. Denervation and type II fiber atrophy may contribute to the muscle dysfunction in patients with PAD and further confirm that the pathophysiology of chronic PAD extends beyond arterial obstruction.

Arteries↗
PubMed1993

Functional benefits of peripheral vascular bypass surgery for patients with intermittent claudication.

Many patients with peripheral arterial disease (PAD) undergo peripheral bypass surgery to relieve the symptom of intermittent claudication. However, measurement of graft patency alone, assessed by change in ankle blood pressure, may not adequately reflect the improvement in functional status following the operation. Fourteen patients with moderately severe intermittent claudication were evaluated before and after bypass surgery to asses changes in hemodynamics (by resting ankle-brachial indices-ABIs), exercise performance (by a graded treadmill protocol), and community-based walking ability (by a questionnaire that characterizes self-reported walking speed and distance). Six weeks after surgery, resting ABIs improved in surgical patients (from 0.56 +/- 0.09 to 0.93 +/- 0.16, P < 0.05). Peak treadmill walking time improved from 6.2 +/- 5.9 to 11.8 +/- 7.1 min (90%), peak oxygen consumption from 15.5 +/- 6.5 to 19.1 +/- 8.5 mL/kg/min (23%), and pain-free walking time from 1.5 +/- 0.4 to 6.0 5.5 min (290%). Questionnaire scores for walking distance improved by 203% and for walking speed by 130% (all P < 0.05). After twelve weeks, improvements other than pain-free walking time were maintained. Changes in peak treadmill performance or questionnaire scores were not correlated with the initial ABI, changes in ABI six or twelve weeks after surgery, or the type or extent of bypass surgery. The results demonstrate that surgical treatment of PAD, indicated for the relief of intermittent claudication, improves exercise performance and self-reported community-based walking ability. The change in functional status of the patient is an important outcome of surgery that cannot be predicted from routine noninvasive testing alone and should be measured directly.

Aged↗
PubMed1993

Special populations in cardiovascular rehabilitation. Peripheral arterial disease, non-insulin-dependent diabetes mellitus, and heart failure.

Exercise rehabilitation has traditionally been part of the management of patients with coronary artery disease, particularly in the recovery period from a myocardial infarction or after coronary artery bypass surgery. The benefits of exercise training and formal rehabilitation programs are not limited to patients with coronary artery disease, and special populations described in this article should be considered for rehabilitation services. Patients with PAD are frequently severely limited by claudication pain. Exercise rehabilitation is an effective means to improve exercise performance without the use of drugs or operation. In patients with NIDDM, an exercise program not only improves exercise performance (which is impaired as compared with age-matched controls) but also improves glucose metabolism and insulin sensitivity. Patients with left ventricular dysfunction have a severely limited peak exercise performance. In these patients, an exercise program can be conducted safely in a supervised setting and will result in a significant improvement in peak oxygen consumption.

Arterial Occlusive Diseases↗
PubMed1992

Carnitine metabolism during exercise in patients on chronic hemodialysis.

Patients on hemodialysis (HD) have impaired exercise performance. Carnitine homeostasis is also abnormal in this population. As carnitine is an important cofactor for muscle energy metabolism, exercise performance and skeletal muscle carnitine metabolism were characterized in eight HD patients, and in five age-matched controls. Each patient underwent graded bicycle exercise testing to define maximal performance, and prolonged exercise at 70% of their peak work capacity. Muscle (vastus lateralis) total carnitine content (carnitine plus all acylcarnitines) at rest was lower in HD patients than in controls (2320 +/- 1190 vs. 3800 +/- 940 nmol/g, P less than 0.05). In patients on HD, muscle carnitine content was inversely correlated to time on HD (r = -0.74, P less than 0.05), and positively correlated to peak exercise performance (r = 0.77, P less than 0.05). In patients on HD, 8 +/- 7% of the muscle carnitine pool at rest was short-chain acylcarnitines (similar to the distribution in controls), but 32 +/- 5% of the plasma carnitine pool consisted of short-chain acylcarnitines. With high-intensity exercise in patients on HD, muscle short-chain acylcarnitine content increased from 130 +/- 130 to 1380 +/- 820 nmol/g (P less than 0.01). The change in muscle short-chain acylcarnitine content with exercise was correlated with the increase in muscle lactate content (r = 0.88, P less than 0.01). In summary, patients on HD had a lower muscle total carnitine content than control subjects which was correlated to exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The role of hemodynamics and duplex ultrasound in the diagnosis of peripheral arterial disease.

Recent reports have suggested that duplex ultrasound should replace hemodynamic measurements and the use of the ankle-to-arm systolic blood pressure ratio in evaluating patients with peripheral arterial disease. Measurement of peripheral hemodynamics in patients with peripheral arterial disease is well established and can be used for screening populations at risk for peripheral arterial disease; the finding of an abnormal ankle-to-arm ratio is associated with a high risk of cardiovascular morbidity and mortality. With the ankle-to-arm ratio, the diagnosis of vascular disease can be established in symptomatic patients and initial treatment plans can be formulated. In contrast, duplex ultrasound provides accurate information on vessel morphology and changes in blood-flow velocity in specific areas of stenosis. The test is noninvasive, and in some situations the duplex instrument may be superior to an angiogram in detecting patent distal vessels. Because it is more expensive and time-intensive than measuring peripheral pressures, duplex ultrasound should be used in selected patients in whom the knowledge of actual vessel morphology is critical to the patient's treatment.

Ankle↗
PubMed1992

Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease.

Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Contemporary treatment of venous lower limb ulcers.

The postphlebitic syndrome is a significant management problem that affects a large number of patients. Primary prophylaxis of deep-vein thrombophlebitis would reduce the risk of developing the postphlebitic syndrome and should be considered in high-risk patients. Patients who have had a phlebitis should be monitored with noninvasive tests of the deep venous circulation for the development of venous valve incompetence. Patients with venous hypertension should be placed in compression stockings to prevent the postphlebitic syndrome. In patients who progress to venous ulceration, several aggressive measures must be undertaken. Systemic treatment includes management of obesity, edema, immobility, poor nutrition, and comorbid illnesses. Some patients may require a short hospitalization of bed rest, lower limb elevation, and daily dressings and wound care. Outpatient therapy requires sustained compression of 35 to 40 mmHg at the ankle for many months to allow the ulcer to heal. The standard bandage material is Unna's boots, which is applied every one to two weeks by a trained nurse. Cadexomer iodide is an effective local treatment that helps debride the ulcer and accelerate healing. Finally, pentoxifylline therapy has also been shown to significantly improve the healing of venous ulcers.

Bandages↗
PubMed1992

Muscle denervation in peripheral arterial disease.

Muscle function is often severely impaired in peripheral arterial disease (PAD), but the effects of repeated ischemic events upon nerve and muscle are incompletely characterized. We performed comprehensive electrophysiologic studies and skeletal muscle histologic analysis in six patients with unilateral PAD and five control subjects matched for age and activity level. In the PAD patients, all ischemic legs showed both electrophysiologic and histologic evidence of chronic partial denervation-reinnervation restricted to distal muscles. Two of the PAD patients had evidence of milder distal denervation in the nonischemic legs. Two of the controls had denervation in at least one leg, but in each case electrophysiologic findings were pathognomonic of L-5 and S-1 radiculopathies. All other control legs and nonischemic legs were normal. These results suggest that recurrent ischemia associated with PAD may cause muscle denervation, which may be one of the mechanisms responsible for decreased exercise performance in these patients.

Action Potentials↗
PubMed1991

Short-term effects of estrogen and progestin on blood pressure of normotensive postmenopausal women.

Blood pressure rises in women with increasing age, possibly related to the decrease in production of female hormones that accompanies menopause. Although estrogen or progestin administration alone consistently does not lower blood pressure in postmenopausal women, possible interactions of these two hormones in affecting blood pressure are not well understood. We studied 12 surgically postmenopausal, normotensive women, aged 51 +/- 2 years (SEM). Treatment for each subject consisted of 1 week each of placebo, estrogen (conjugated equine estrogens, 2.5 mg/day), progestin (medroxyprogesterone acetate, 60 mg/day), and combined estrogen and progestin, given in varied order. At the end of each week, auscultatory blood pressures were measured while patients were seated. Neither estrogen nor progestin alone either increased or decreased blood pressure significantly, whereas combined estrogen and progestin lowered systolic, diastolic, and mean blood pressures 6 to 7 mm Hg (P less than .05). Treatment order was unrelated to the change in blood pressure values. The authors suggest that administering progestin with estrogen may be more effective in lowering blood pressure than either hormone alone in postmenopausal women.

Blood Pressure↗
PubMed1991

Exercise physiology in cardiovascular diseases.

Exercise testing protocols and training regimens are well established for patients recovering from myocardial infarction or coronary artery bypass surgery. However, exercise rehabilitation programs for patients with peripheral arterial disease or left ventricular dysfunction with congestive heart failure have not been well developed. Several recent reports have established reproducible exercise testing protocols with objective measures of performance for patients with peripheral arterial disease and congestive heart failure. Using these testing methods to define changes in exercise capacity, exercise training programs have been shown to result in a significant increase in exercise performance and community-based quality of life. The mechanism of improvement appears to involve peripheral adaptations in skeletal muscle metabolism rather than increases in cardiac output or peripheral blood flow.

Coronary Disease↗
PubMed1991

Developmental analysis of elongation factor-1 alpha expression in transgenic tobacco.

The developmental regulation of the translational elongation factor EF-1 alpha has been analyzed in tobacco. A gene fusion was constructed consisting of the 5' and 3' regions of the tomato genomic clone LeEF-A from the EF-1 alpha gene family and the beta-glucuronidase coding region. Analysis of the transgenic plants containing this chimeric gene demonstrated that the tomato LeEF-A flanking sequences were sufficient to confer expression patterns similar to those of the endogenous tobacco EF-1 alpha gene. The patterns of beta-glucuronidase activity in this system indicated that during plant growth and development EF-1 alpha is regulated with increased expression corresponding to regions of high protein synthesis, including meristems, rapidly growing tissues, and developing gametophytes. In addition, EF-1 alpha expression responds rapidly to changes in growth patterns induced by hormone treatment. Our results are in agreement with studies in animals indicating that EF-1 alpha expression may be rate limiting for protein synthesis and demonstrate that the analysis of EF-1 alpha is of value for studying interrelationships between protein synthesis and developmental control.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1991

Isolation, sequence, and expression in Escherichia coli of the Pseudomonas sp. strain ACP gene encoding 1-aminocyclopropane-1-carboxylate deaminase.

Pseudomonas sp. strain ACP is capable of growth on 1-aminocyclopropane-1-carboxylate (ACC) as a nitrogen source owing to induction of the enzyme ACC deaminase and the subsequent conversion of ACC to alpha-ketobutyrate and ammonia (M. Honma, Agric. Biol. Chem. 49:567-571, 1985). The complete amino acid sequence of purified ACC deaminase was determined, and the sequence information was used to clone the ACC deaminase gene from a 6-kb EcoRI fragment of Pseudomonas sp. strain ACP DNA. DNA sequence analysis of an EcoRI-PstI subclone demonstrated an open reading frame (ORF) encoding a polypeptide with a deduced amino acid sequence identical to the protein sequence determined chemically and a predicted molecular mass of 36,674 Da. The ORF also contained an additional 72 bp of upstream sequence not predicted by the amino acid sequence. Escherichia coli minicells containing the 6-kb clone expressed a major polypeptide of the size expected for ACC deaminase which was reactive with ACC deaminase antiserum. Furthermore, a lacZ fusion with the ACC deaminase ORF resulted in the expression of active enzyme in E. coli. ACC is a key intermediate in the biosynthesis of ethylene in plants, and the use of the ACC deaminase gene to manipulate this pathway is discussed.

Amino Acid Sequence↗