The goals of our clinical research are

• to establish the most effective exercise prescription in health and disease
• to understand the mechanisms in which exercise/physical activity prevents and treats modern chronic disease

The current diseases of interest include hypertension, diabetes, and obesity.

The measurement of endothelial function is a new direction for our laboratory. We are applying this measurement of artery health to the postprandial period for the purpose of studying the effects of physical activity on the postprandial endothelial dysfunction.

Ryan Harris (2007 Graduate) is measuring endothelial function in a subject

In 2005, our research focus reached a new level with the incorporation of the measurement of Brachial Artery Flow-Mediated Dilation (FMD). In the past, our disease outcomes were classic risk factors for atherosclerotic cardiovascular disease; i.e. cholesterol, blood pressure, and/or blood sugar. With our new technology, we can now observe the nature of a single layer of cells in the artery, the endothelium. The endothelium is the site where atherosclerotic cardiovascular disease begins. The endothelium is responsible for maintaining vascular functions that protect the artery from disease. Life-style factors, such as diet or smoking, insult the endothelium compromising its ability to protect the artery, leading to heart disease, stroke, and peripheral vascular disease.

A simple illustration of the measurement of endothelial function using the flow-mediated dilation of the brachial artery is below.

Although the focus of our research is in the postprandial endothelial function and exercise, our graduate students are actively involved in supplemental endothelial function studies.

• Ryan Harris (2007 Graduate) published our first manuscript on the effects of repetitive reactive hyperemia on flow-mediated dilation in Vascular Medicine last year. He found that repetitive measurements of flow-mediated dilation did not affect the outcome. For us, this is good news. The future of our work in endothelial function requires repetitive measurements following exercise.
• Jaume Padilla (Doctoral Candidate) investigated the technique to measure flow mediated dilation. He compared the traditional reactive hyperemia technique to a hand-grip method to cause hyperemia. He found that the two techniques did not produce the same results; the traditional reactive hyperemic technique was the more accurate and valid technique. He has published this study in Clinical Science

• Ryan Harris (2007 Graduate) established the reproducibility of brachial artery FMD following exercise. He found FMD to be reproducible; quite important for researchers working on exercise related studies. This study has been published in Ultrasound, Medicine and Biology.
• Both Ryan and Jaume observed the shear stress of blood flow during the recovery from exercise and found shear stress not only to be intensity dependent, but last for two hours post-exercise. This finding is important in that the shear stress created by the blood flow may be one of the mechanisms to improve arterial health with exercise. This manuscript has been published in Vascular Medicine.
• The Team wrote our first review article on the efficacy of measuring brachial artery FMD in the acute exercise model. This article has been published in Cardiovascular Ultrasound.

Brachial artery response to high-fat meal alone (square and dotted line), a low-fat meal alone (square and dotted line) and high-fat meal combined with physical activity (triangle and solid line). * Indicates significant difference (P=0.005) from pre-meal; # Indicates significant difference (P=0.001) from 4 h post-high-fat meal

When combining both groups, a significant inverse relationship was found between postprandial plasma SOD activity and the attenuation of FMD following the high-fat meal (r= -0.674; p= 0.008).

We are currently investigating the oxidative stress between the two groups.

On those same lines, we investigated the SOD activity response to a high-fat meal in healthy active adults.

Sixteen adults (5 men and 11 women; age 27.8 ±1.5 yrs; BMI= 23.4±0.50 kg/m2) were fed a high-fat meal. SOD activity was assessed at baseline (before the meal) and four hours after the meal. We found a significant increase in SOD activity following the high-fat meal (pre=8.16±0.19 to post=9.25±0.25 U/mL (p=0.044).

The applications of these two studies support exercise and physical activity to protect the artery from the detrimental effects of a high-fat meal. We believe exercise and physical activity work through antioxidant mechanisms.

To apply our theories on the antioxidant capacities of exercise and physical activity in overweight and obesity, we have compared the brachial artery FMD response to a single session of exercise in sedentary and active overweight men. We know that sedentary overweight men exhibit excessive oxidative stress to a single session of exercise. We also know that physical activity helps prevent cardiovascular disease in overweight men, despite the excess weight. Again, we believe, it's the antioxidant defenses that are increased in overweight active men that protect the artery.

So, we also observed the inflammatory response to the single session of exercise and it's effect on arterial health as measured by brachial artery FMD.

Subjects exercised at intensities of 25%, 50%, and 75% on a treadmill. FMD and bloods were measured before and one hour after exercise.

Active overweight men exhibited a significant increase (p=0.034) in brachial artery FMD following physical activity, whereas sedentary overweight adults exhibited a significant decrease (p=0.010). We definitely have a found a significant difference in the arterial response to exercise between sedentary and active overweight men. We know we cannot attribute this difference to the inflammatory response as we found no differences in IL-6 or TNF-alpha.

We believe this difference is due to oxidative stress and the antioxidant defense associated with habitual exercise or physical activity. We are observing the oxidative stress now.

This study has been published in Obesity Research.

Our recent publications in endothelial function include:

1. Padilla, J., R.A. Harris, L.D. Rink, and J.P. Wallace. Characterization of the brachial artery sheer stress following walking exercise. Vascular Medicine, 13:105-111, 2008.
2. Harris, R.A., J. Padilla K.P. Hanlon, L.D. Rink, J.P. Wallace. Reproducibility of the Flow-Mediated Dilation Response to Acute Exercise in Overweight Men, Ultrasound and Medicine and Biology, 16:578–584, 2008.
3. Harris, R.A., Padilla, J., Hanlon, K.P., Rink, L.D., J.P Wallace. The Flow-Mediated Dilation Response to Acute Exercise in Overweight Active and Inactive Men, Obesity Research, 16:578–584, 2008.
4. Padilla, J., R.A. Harris, and J.P. Wallace. Can the measurement of brachial artery flow-mediated dilation be applied to the acute exercise model? Cardiovascular Ultrasound, 5:45-52, 2007.
5. Padilla, J., R.A. Harris, A.D. Fly, L.D. Rink, and J.P. Wallace. The effect of acute exercise on endothelial function following a high-fat meal, European Journal of Applied Physiology, 98:256-262, 2006.
6. Padilla, J., R.A. Harris, A.D. Fly, L.D. Rink, and J.P. Wallace, A comparison between active and reactive hyperemia-induced brachial artery vasodilation, Clinical Science, 110:387-392, 2006.
7. Harris, R.A., J. Padilla, and J.P. Wallace. Variability of flow-mediated dilation measurements with repetitive reactive hyperemia, Vascular Medicine, 11:1-6, 2006.
8. Harris, RA, J Padilla, JP Wallace, The Effect of Repetitive Reactive Hyperemia on Brachial Artery Flow Mediated Dilation Measurements, Medicine & Science in Sports & Exercise, 37(5) Supplement:S221-S222, 2005
9. Padilla, J., R. Harris, JP Wallace, The Variation of Flow Mediated Dilation During Morning Hours, Medicine & Science in Sports & Exercise, 37(5) Supplement:S221, 2005.

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Our most recent efforts in hypertension have been to compare exercise to physical activity in the nonpharmalogical treatment of hypertension.

Using ambulatory blood pressure monitoring (pictured to the right), we are able to measure blood pressure for 24 hours. We obtain a total of 100 blood pressures, measuring it every 15 min during the day and every 30 min during sleep.

Illustrated above is a typical blood pressure pattern of an adult with hypertension. The systolic blood pressure is illustrated in red; the diastolic in yellow; and the normal pressures in green. Normal blood pressure should be below 140/90 mm Hg during the waking hours and below120/80 mm Hg during the sleeping hours.

With this technology we have observed the value of the time of day to exercise on the blood pressure reduction. We have also identified adults with nocturnal high blood pressure. The tracing above is an adult with normal nocturnal blood pressure.

Jaume Padilla, as a masters student from the University of Leuven, completed a study in which he measured the ambulatory blood pressures during life-style physical activity. His subjects wore the ambulatory monitor while doing yard work and house work. We found that simple life-style activities such as mowing the lawn, etc. lowered blood pressure quite effectively in both prehypertension and hypertension. His work was published in Medicine and Science in Sports and Exercise.

Our most recent articles in exercise and hypertension are:

1. Park, S., L.D. Rink, and J.P. Wallace. Accumulation of physical activity: blood pressure reduction between 10-min walking sessions. Journal of Human Hypertension, 22:475-482, 2008.
2. Wallace, J.P. and A. Fly. Lifestyle: Sound Medicine for high blood pressure. ACSM’s Health & Fitness Journal, 12(2):8-15, 2008.
3. Park, S. D.L. Rink and J.P. Wallace. The accumulation of physical activity leads to a greater blood pressure reduction than a single continuous session in prehypertension, Journal of Hypertension 24:1761-1770, 2006.
4. Lehmkuhl, L.A.A., S. Park, D. Zakutansky, D. Tanner, J. Stager, C.A. Jastremski and J.P. Wallace, Reproducibility of postexercise ambulatory blood pressure in Stage I hypertension. Journal of Human Hypertension 19:589-595, 2005.
5. Wallace, J.P., S. Park, D.W. Zakutansky, L.A.A. Lehmkuhl, and C.A. Jastremski, Time of day to monitor ambulatory blood pressure affects the outcome. Blood Pressure Monitoring 10:43-50, 2005
6. Park, S., C.A. Jastremski, and J.P. Wallace, Time of day for exercise on blood pressure reduction in dipping and nondipping hypertension, Journal of Human Hypertension 19:597-605, 2005.
7. Padilla, J., J.P. Wallace, and S. Park, Accumulation of physical activity reduces blood pressure in pre- and hypertension, Medicine and Science in Sports and Exercise, 37:1264-1275, 2005.
8. Wallace, J.P., Exercise in Hypertension: A Clinical Review. Sports Medicine, 33(8):585-598, 2003.
9. Wallace, J.P., P.G. Bogle, B.A. King, J.B. Krasnoff, and C.A. Jastremski, The magnitude and duration of ambulatory blood pressure reduction following acute exercise. Journal of Human Hypertension,13:361-366, 1999.

Our experience with exercising adults with diabetes led us to investigate the efficacy of exercise in treating diabetic neuropathy.

Diabetic neuropathy is a complication of diabetes where the nerve becomes deficient in conducting impulses. Neuropathy affects both the sympathetic and peripheral nerves. Neuropathy of the peripheral nerves compromises sensation (such as touch) and motor control (such as gait). Neuropathy of the sympathetic nerves affects anything having to do with autonomic control. In terms of exercise, autonomic neuropathy affects the heart rate, blood pressure, blood flow distribution response to exercise. It also affects the ability to sense angina and hypoglycemia.

Several adults with diabetes who exercised in our programs reported they could feel their feet again and wanted to go dancing. Apparently there was something about the exercise that was changing their neuropathy. We believed it was the improvement in blood flow associated with exercise. So, we set out to do a series of studies to investigate the influence of exercise on blood flow and nerve function.

Franz Jones (Master's student 2006) and Don Zakutansky (doctoral graduate 2006) conducted an experiment which altered blood flow of the calf and observed the nerve function during the different levels of blood flow.

The conditions of blood flow variability are:

• ischemia
• reactive hyperemia
• exercise

Our most recent publications are:

1. Zakutansky, D.W., K Kitano, J.P. Wallace, and D.M. Koceja, H-Reflex and motor responses to acute ischemia in apparently healthy individuals, Journal of Clinical Neurophysiology 22:210-215, 2005
2. Zakutansky, DW, Kitano, K, Park,SJ, Koceja, DM, Wallace, JP. Sensory and Motor Responses to Acute Ischemia in Healthy Individuals, Medicine and Science in Sport and Exercise 36(5) Supplement:S165, May 2004
3. Zakutansky, D.W. and J.P. Wallace, Relationships among physical activity, limb blood flow, and autonomic neuropathy tests in adults with diabetes, Medicine and Science in Sports and Exercise, 33:S21, 2001
4. King, B.A., J.P. Wallace, and R.A. Kaplan. The relationship between VO2max and autonomic neuropathy. Medicine and Science in Sport and Exercise 29 (Suppl 5): S90, 1997.

Our obesity research began in 1992 when Dr. Wayne Miller joined our research team. Dr. Miller created the Non-Diet Diet and integrated it into our Weight Loss Clinic, administered through the Adult Fitness Program.

One of our current research directions in obesity is directed at the influences of diet and exercise on endothelial health.

In addition, we are also working through a behavioral approach to healthy diet and exercise with Drs. Susan Middlestadt and Alyce Fly in Applied Health Sciences. Dr. Middlestadt, a social behaviorists, is leading the team to find out the success factors to healthy eating and exercise/physical activity.

Publications from our obesity research:

1. Wallace, J.P., Obesity, in American College of Sports Medicine: Exercise Management for Persons with Chronic Diseases and Disabilities, Human Kinetics Publishers, Champaign, 2002.
2. Miller, W.C., T. Swenson, and J.P. Wallace, Derivation of prediction equations for residual volume in overweight men and women. Medicine and Science in Sport and Exercise, 30:322-327, 1998.
3. Miller, W.C., M.G. Niederpruem, J.P. Wallace, and A.K. Lindeman, Dietary fat, sugar, and fiber predict body fat content. Journal of the American Dietetic Association 94:612-615, 1994.
4. Wallace, J.P., P.K. Bogle, K. Murray and C.A. Jastremski, Variation in anthropometric dimensions for estimating upper and lower body obesity. American Journal of Human Biology 6:699-709, 1994.
5. Miller, W.C., J.P. Wallace, and K. E. Eggert, Predicting max HR and HR-V02 relationship for exercise prescription in obesity. Medicine and Science in Sport and Exercise 25:1077-1081, 1993.
6. Miller, W.C., J.P. Wallace, A.K. Lindeman and C. Jastremski, Successful weight loss in a self-taught, self-administered program. International Journal of Sports Medicine 14:401-405, 1993.
7. Miller, W.C., J.P. Wallace, K.E. Eggert and A.K. Lindeman, Cardiovascular risk reduction in self-taught, self-administered weight-loss program called the Non-Diet Diet. Medicine, Exercise, Nutrition, and Health 2:218-223, 1993.
8. Miller, W.C., A.K. Lindeman, J.P. Wallace, and M. Niederpruem, Diet composition, caloric intake, and exercise in relation to body fatness, American Journal of Clinical Nutrition 52:426 430, 1990.
   
   

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