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Biomedical subjects

W R Hiatt

Publications and source records attributed to W R Hiatt.

At least 55 records · Page 3Linked to original sources
PubMed1998

Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.

Persons with type II diabetes mellitus (DM), even without cardiovascular complications have a decreased maximal oxygen consumption (VO2 max) and submaximal oxygen consumption (VO2) during graded exercise compared with healthy controls. We evaluated the hypothesis that change in the rate of VO2 in response to the onset of constant-load exercise (measured by VO2-uptake kinetics) was slowed in persons with type II DM. Ten premenopausal women with uncomplicated type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had a VO2 max test. On two separate occasions, subjects performed 7-min bouts of constant-load bicycle exercise at workloads below and above the lactate threshold to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of heart rate rise). VO2 max was reduced in subjects with type II DM compared with both lean and overweight controls (P < 0.05). Subjects with type II DM had slower VO2 and heart rate kinetics than did controls at constant workloads below the lactate threshold. The data suggest a notable abnormality in the cardiopulmonary response at the onset of exercise in people with type II DM. The findings may reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.

Adult↗
PubMed1997

Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease.

Supervised, hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease. However, it has been suggested that unsupervised, home-based exercise programs, which have been relatively little evaluated, would be equally efficacious as compared with hospital-based programs. The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise performance more than a home-based program. Of 20 consecutively enrolled patients with claudication, 10 were randomly placed into a supervised, hospital-based program and 10 into an unsupervised, home-based program for a three-month period. Exercise performance was evaluated by treadmill testing using a graded protocol. In addition, functional status was evaluated by the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study SF-20 questionnaire (MOS). Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit. Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with the program. Patients in the hospital-based group improved peak walking time by 137%, pain-free walking time by 150%, and peak oxygen consumption by 19% (all P < 0.05). Patients reported an improved walking distance and speed according to WIQ data (both P < 0.05). In addition, the MOS physical functioning score in the hospital-based group improved by 20 percentage points (P < 0.05). In contrast, patients in the home-based program did not improve exercise performance measured on the treadmill. Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home-based program (P < 0.05). The ability to walk distances was the only questionnaire measure that improved in persons who received the home-based program (P < 0.05). Preliminary results suggest that a supervised, hospital-based program is more effective for improving treadmill exercise performance than an unsupervised, home-based program.

Ambulatory Care↗
PubMed1997

Exercise testing and exercise rehabilitation for patients with peripheral arterial disease: status in 1997.

Intermittent claudication is a common manifestation of peripheral arterial occlusive disease (PAOD). Patients with claudication are limited in terms of work, housework and leisure activities so that functional status is very impaired. Therefore, the goals for treatment should focus on improving the functional impairment as well as on modifying risk factors. Evaluation of the functional status is of critical importance before beginning any therapy so that any resultant changes can be assessed. A validated graded treadmill protocol and validated questionnaires are used for this purpose. Three questionnaires that are currently used include the Walking Impairment Questionnaire, the PAOD Physical Activity Recall and the Medical Outcomes Study SF-36. Exercise rehabilitation is a method that has been particularly efficacious for treating the functional impairment associated with intermittent claudication. Exercise rehabilitation has been shown to improve pain-free treadmill walking distance by 44% to 300% and absolute walking distance by 25% to 442%. In addition, improvements have also been reported (using questionnaire data) in the ability to walk distances and speeds, in amount of habitual physical activity and in physical functioning. Thus, exercise rehabilitation has caused improvements not only in exercise capacity but also in community-based functional status. Because of the benefits of this treatment, in addition to the low associated morbidity, exercise therapy is recommended as an important treatment option for people with intermittent claudication due to PAOD.

Animals↗
PubMed1997

Current and future drug therapies for claudication.

The primary objectives of claudication treatment are to reduce cardiovascular mortality and improve walking ability. Patients with claudication have 60% mortality over 10 years, with most deaths due to myocardial infarction and stroke. Aggressive risk-factor modification is required in all these patients, particularly smoking cessation, lipid modification, and treatment of hypertension, diabetes and elevated homocysteine levels. Aspirin, ticlopidine and clopidogrel are all effective in reducing the risk of myocardial infarction, stroke and vascular death, and thus antiplatelet therapy should be considered in all claudicants. Patients with disabling claudication should be considered for therapies that relieve claudication pain and improve exercise performance, the most effective being exercise training and smoking cessation. Pentoxifylline, the only approved claudication drug in the United States, has modest efficacy in improving treadmill exercise performance. Other drugs shown to be of some benefit in patients with claudication include propionyl-L-carnitine, cilostazol and possibly prostaglandin derivatives. Several antiplatelet agents and angiogenic growth factors are also being evaluated for the treatment of claudication.

Enzyme Inhibitors↗
PubMed1996

Exercise training improves functional status in patients with peripheral arterial disease.

PURPOSE: In patients with intermittent claudication (IC) a structured walking exercise program improves exercise performance. However, few studies have evaluated the effects of exercise training on functional status during daily activities. We hypothesized that a supervised exercise training program would improve functional status in patients with IC, with 24 weeks of training more beneficial than 12 weeks. A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status. METHODS: Twenty-nine men with disabling IC were randomized to 12 weeks of either supervised treadmill training (3 hr/wk at a work intensity sufficient to produce claudication), strength training (3 hr/wk of resistive training of six muscle groups of each leg), or to a nonexercising control group. Functional status was assessed by questionnaires characterizing walking ability (Walking Impairment Questionnaire, WIQ), habitual physical activity level (Physical Activity Recall, PAR), and physical, social, and role functioning, well-being, and overall health (Medical Outcomes Study SF-20, MOS). Patients alos had their activity levels monitored with an activity monitor (Vitalog). RESULTS: After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk, the MOS physical functioning score by 24 percentage points, and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr (all p < 0.05). No changes were seen in WIQ scores. After 12 additional weeks of treadmill training improvements initially observed in the PAR, MOS, and Vitalog scores were maintained, and in addition the ability to walk distances (WIQ) improved by 31 percentage points, and the IC severity score had improved by 29 percentage points (both p < 0.05). After 12 weeks of strength training patients improved their WIQ walking speed, stair climbing scores, and MOS well-being scores with no other changes in functional status. Subjects in the control group did not improve functional status by any measure. Twelve weeks of treadmill training after the strength training program maintained WIQ walking speed scores, and activity level defined by Vitalog improved. Twelve weeks of combined treadmill and strength training after the control period had no effect on functional status. CONCLUSIONS: A supervised treadmill training program improved functional status during daily activities, with 24 weeks more effective than 12. In addition, treadmill training alone was more effective in improving functional status in patients with IC than strength training or combinations of the training modalities.

Aged↗
PubMed1996

Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease.

Patients with symptomatic peripheral arterial occlusive disease have a claudication-limited peak exercise performance that is improved with exercise training. The effects of training on skeletal muscle metabolism were evaluated in 26 patients with claudication, randomized into a 12-wk program of treadmill training (enhances muscle metabolic activity in normal subjects), strength training (stimulates muscle hypertrophy in normal subjects), or a nonexercising control group. Gastrocnemius muscle biopsies were performed at rest and before and after training. After 12 wk, only treadmill training improved peak exercise performance and peak oxygen consumption. Treadmill training did not alter type I or type II fiber area and did not increase citrate synthase activity but was associated with an increase in the percentage of denervated fibers (from 7.6 +/- 5.4 to 15.6 +/- 7.5%, P < 0.05). Improvement in exercise performance with treadmill training was associated with a correlative decrease in the plasma (r = -0.67) and muscle (r = -0.59) short-chain acylcarnitine concentrations (intermediates of oxidative metabolism). Patients in the strength and control groups had no changes in muscle histology or carnitine metabolism, but strength-trained subjects had a decrease in citrate synthase activity. Thus treadmill training increased peak exercise performance, but this benefit was associated with skeletal muscle denervation and the absence of a "classic" mitochondrial training response (increase in citrate synthase activity). The present study confirms the relationship between skeletal muscle acylcarnitine content and function in peripheral arterial occlusive disease, demonstrating that the response to treadmill training was associated with parallel improvements in intermediary metabolism.

Aged↗
PubMed1995

Quantification of carnitine, acetylcarnitine, and total carnitine in tissues by high-performance liquid chromatography: the effect of exercise on carnitine homeostasis in man.

A method for the quantitative determination of carnitine, acetylcarnitine, and total carnitine in tissue was developed for application to clinical research and diagnosis. Human skeletal muscle and heart specimens (10-20 mg) were homogenized in 1 ml of water. Aliquots of the resulting homogenates (50 microliters) were extracted with 1.0 ml of acetonitrile:methanol (3:1) and the carnitine-related compounds were isolated using columns containing 300 mg of silica gel. Samples were then derivatized with 4'-bromophenacyl trifluoromethanesulfonate for spectrophotometric detection or 2-(2,3-naphthalimino)ethyl trifluoromethanesulfonate for fluorescence detection and quantified by high-performance liquid chromatography. Fluorometric detection of 2-(2,3-naphthalimino)ethyl ester derivatives afforded a 500-fold increase in sensitivity when compared to derivatization with 4'-bromophenacyl trifluoromethanesulfonate. This methodology permitted detection of acetylcarnitine in dilute human muscle homogenates at quantities of 790 fmol of acetylcarnitine injected. The method was applied to a series of human skeletal muscle biopsy samples obtained from subjects performing exercise at high work loads. The method permitted quantification of carnitine, acetylcarnitine, and total carnitine (sum of carnitine and all acylcarnitines) and demonstrated the specific redistribution of the carnitine pool from carnitine to acetylcarnitine with exercise above the lactate threshold. This HPLC method is facile, and provides a sensitive and specific approach for use in human biopsy specimens.

Acetophenones↗
PubMed1995

Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study.

BACKGROUND: The ankle/brachial systolic blood pressure index (ABI), a noninvasive measure of peripheral arterial disease (PAD), is widely used in epidemiological studies. However, the normal ranges of the ABI in healthy populations and ABI criteria for the diagnosis of PAD in large population studies have not been critically evaluated. METHODS AND RESULTS: The San Luis Valley Diabetes Study (SLVDS) was designed to evaluate the prevalence and complications of non-insulin-dependent diabetes mellitus (NIDDM) in a biethnic population. The present study was conducted as part of the SLVDS to assess the prevalence of vascular disease in 1280 nondiabetic control subjects and 430 patients with NIDDM. The ABI criteria for PAD were developed in 403 healthy individuals with a low risk for cardiovascular disease. In these low-risk subjects, the average resting ABI value was 0.07 lower in women than in men. In both sexes, the dorsalis pedis ABI was 0.04 lower than in the posterior tibial artery, and the left leg ABI was 0.02 lower than the right leg ABI (all differences, P < .05). In the low-risk subjects, ABI values were lower after exercise than at rest and had similar differences by sex and leg as observed at rest. Using specific abnormal cutoff points for the ABI, we evaluated three criteria for PAD in the overall population: two abnormal vessels in the same leg at rest (both dorsalis pedis and posterior tibial arteries), one abnormal vessel per leg at rest, and an ABI abnormality only after exercise. Subjects classified with PAD by the two-vessel criterion had a higher frequency of claudication and the physical finding of an absent pulse compared with subjects without PAD or patients with PAD defined by the one-vessel or exercise criterion. Use of the two-vessel criterion identified an increased risk of PAD with increasing age, NIDDM, smoking, hypertension, and elevated cholesterol levels. In contrast, the one-vessel PAD criterion was associated only with increasing age and smoking, and exercise-diagnosed PAD was not associated with any cardiovascular risk factor except for male sex. CONCLUSIONS: In low-risk subjects, the normal distribution and lower abnormal cutoff point values of the ABI differed by type of test, sex, ankle vessel, and leg. When these specific abnormal cutoff points were applied to the SLVDS population, the two-vessel abnormal criterion described patients with typical clinical characteristics of PAD and the expected associations of PAD with cardiovascular risk factors. These clinical characteristics and cardiovascular risk factor associations were less evident with PAD diagnosed by the one-vessel or exercise criterion. Therefore, an abnormal dorsalis pedis and posterior tibial ABI in the same leg at rest should be used for the diagnosis of PAD in epidemiological studies.

Adult↗
PubMed1995

Progression of neuropathy in peripheral arterial disease.

Atherosclerotic peripheral arterial disease (PAD) can cause muscle denervation, but whether it is associated with more severe peripheral nerve disease is not clear. Equally unclear is the effect of exercise training on the neuromuscular aspects of this disease. We performed serial electrophysiologic studies (nerve conduction studies and quantitative electromyography) and muscle strength assessment on 16 patients with moderately severe PAD. Seven of the patients were assigned to a natural history (control) group and 9 to an exercise training group. Over study periods ranging from 3 to 23 months, 6 of 7 patients in the control group and 8 of 9 patients in the exercise training group showed progression of multifocal neuropathic disease in their ischemic legs. For equivalent lengths of time, the degree of neuropathic progression was not significantly different between the control and exercise training groups. There was a significant decline in muscle strength for the control group but not for the exercise training group. These results demonstrate that PAD can be associated with the development of a multifocal predominantly motor neuropathy, which is most likely ischemic in etiology. Furthermore, exercise training does not pose an additional risk for the development of neuropathy in patients with moderately severe PAD.

Aged↗
PubMed1995

Exercise rehabilitation for patients with peripheral arterial disease.

Intermittent claudication, resulting from PAD, impairs functional status. Reducing the disability result from the disease is therefore an important goal of treatment. To evaluate the efficacy of an intervention designed to improve functional status requires that appropriate outcome measures be developed to assess all treatments. Such outcome measures include graded treadmill testing and questionnaire assessment. These methodologies are important because they have a high degree of precision and accuracy and are practical and reproducible. Thus, functional status changes resulting from any intervention can be evaluated, and interventions can be compared with one another using the same methodologies. Currently, interventional therapies are often used to treat a portion of patients with claudication [49]. Such therapies restore blood flow and improve functional status, but with a high associated cost: morbidity and mortality. Pharmacological therapies currently are being developed, but the role of drugs in the overall management of claudication needs further study. Importantly, exercise therapy has been shown in numerous studies to be efficacious and very well tolerated by patients. Patients improve both their walking ability in the laboratory and their community-based functional status. Because of the efficacy of this treatment, in addition to the low associated morbidity, exercise therapy is recommended as a major treatment option for persons with intermittent claudication due to PAD.

Arteriosclerosis↗
PubMed1995

Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise.

Persons with non-insulin-dependent diabetes mellitus (NIDDM), in the absence of complications, have a decreased exercise performance compared with nondiabetic subjects. However, degree of impairment and factors associated with reduced exercise performance have not been fully characterized. Maximal exercise performance using a graded treadmill protocol was assessed in 10 sedentary persons with uncomplicated NIDDM (aged 51 +/- 7) and 10 healthy age- and activity-matched controls. Potential correlates of exercise performance measured included fasting and post-exercise glucose concentrations and fasting insulin concentration, hemoglobin A1C, hematocrit, and whole blood viscosity. At maximal exercise, diabetic persons had a 24% lower maximal walking time and 20% lower maximal VO2 than controls (both P < 0.05), while hemodynamic measures did not differ between groups. During graded exercise, at work loads below the maximal one, the relationship between VO2 and work load was significantly lower in persons with NIDDM than controls by an average of 16%. No correlations were found between peak exercise performance and any of the potential correlates of exercise performance measured. We conclude that persons with NIDDM have an impaired peak exercise performance not associated with degree of glycemic control. The reduced rate of increase in oxygen consumption during increasing submaximal work loads in NIDDM suggests that limitations in oxygen delivery may impair exercise performance in otherwise healthy persons with diabetes.

Age Factors↗
PubMed1995

Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise.

Persons with non-insulin-dependent diabetes mellitus (NIDDM), in the absence of complications, have a decreased exercise performance compared with nondiabetic subjects. However, degree of impairment and factors associated with reduced exercise performance have not been fully characterized. Maximal exercise performance using a graded treadmill protocol was assessed in 10 sedentary persons with uncomplicated NIDDM (aged 51 +/- 7) and 10 healthy age- and activity-matched controls. Potential correlates of exercise performance measured included fasting and post-exercise glucose concentrations and fasting insulin concentration, hemoglobin A1C, hematocrit, and whole blood viscosity. At maximal exercise, diabetic persons had a 24% lower maximal walking time and 20% lower maximal VO2 than controls (both P < 0.05), while hemodynamic measures did not differ between groups. During graded exercise, at work loads below the maximal one, the relationship between VO2 and work load was significantly lower in persons with NIDDM than controls by an average of 16%. No correlations were found between peak exercise performance and any of the potential correlates of exercise performance measured. We conclude that persons with NIDDM have an impaired peak exercise performance not associated with degree of glycemic control. The reduced rate of increase in oxygen consumption during increasing submaximal work loads in NIDDM suggests that limitations in oxygen delivery may impair exercise performance in otherwise healthy persons with diabetes.

Adult↗
PubMed1994

Carnitine metabolism during exercise.

Carnitine is an important cofactor for normal cellular metabolism. Optimal utilization of fuel substrates for ATP generation by skeletal muscle during exercise is dependent on adequate carnitine stores. During short periods of exercise the skeletal muscle carnitine pool is largely segregated from extracellular carnitine. In normal human subjects, only minimal changes in the muscle carnitine pool are observed during exercise at work loads below the lactate threshold. In contrast, at work-loads above the lactate threshold the muscle total carnitine is redistributed from carnitine to acetylcarnitine, with the acetylcarnitine content correlated with the muscle acetyl-CoA and lactate contents. In contrast, in patients with peripheral arterial disease, an accumulation of acylcarnitines is observed at all work loads. Patients with chronic renal failure who are on hemodialysis demonstrate a poor exercise capability which is correlated with a decrease in muscle carnitine content. Carnitine supplementation has been shown to improve exercise tolerance in both peripheral arterial disease and hemodialysis patients. Further work is needed to define the mechanism by which exogenous carnitine improves exercise performance in order to better define potential patient populations for therapy and to facilitate optimal dosing regimens.

Acetyl Coenzyme A↗