The central theme of our proposal is to understand mechanisms of exercise intolerance in Chronic Heart Failure (CHF) and to ultimately use this information to help guide rehabilitation and medical management of this growing population. This is of importance because, the incidence of CHF increases 50-fold between the ages of 40 and 60 years and the disease is the nation's most rapidly growing cardiovascular disorder.
Two specific aims focused on heart and lung interactions will be addressed. First, we will test the hypothesis that breathing during exercise influences cardiac function. We will test this by, a) examining the influence of transient and sustained increases in lung volume on cardiac function during exercise using continuous positive airway pressure, expiratory threshold loading and voluntary maneuvers, b) determining the effects of intra-thoracic pressure changes on cardiac output via loading and unloading the respiratory muscles using proportional assist ventilation during exercise, c) examine if a muscle chemosensitive reflex may stimulate ventilation in CHF greater than in controls by using post-exercise leg ischemia, and d) determining if the respiratory muscles """"""""steal"""""""" blood flow from locomotor muscles during exercise by unloading respiratory muscles and measuring leg blood flow. Second, we will examine a neurohumoral basis for structural changes in the pulmonary system and altered exercise tolerance in CHF by examining a polymorphism of a key regulatory enzyme, angiotensin-converting enzyme (ACE, which exists in 2 forms, insertion-Il and deletion-DD alleles). We will test this by, a) determining if the activated renin-angiotensin system in CHF enhances ACE genotype related differences in pulmonary and cardiovascular function relative to controls, b) determining if the altered pulmonary function in the DD genotype of CHF patients is related to alterations in pulmonary vascular tone and permeability and independent of cardiac function c) examining if complete blockade of angiotensin-Il (A-Il) with A-Il receptor blockers will abolish genotype differences in the CHF subjects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071478-02
Application #
6612953
Study Section
Special Emphasis Panel (ZRG1-ALTX-1 (01))
Program Officer
Varghese, Jamie
Project Start
2002-07-10
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$429,941
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Sajgalik, Pavol; Kremen, Vaclav; Fabian, Vratislav et al. (2018) Noninvasive Blood Pressure Monitor Designed for Patients With Heart Failure Supported with Continuous-Flow Left Ventricular Assist Devices. ASAIO J :
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Van Iterson, Erik H; Olson, Thomas P; Borlaug, Barry A et al. (2017) Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction. Med Sci Sports Exerc 49:1758-1768
Van Iterson, Erik H; Snyder, Eric M; Johnson, Bruce D (2017) The Influence of 17 Hours of Normobaric Hypoxia on Parallel Adjustments in Exhaled Nitric Oxide and Airway Function in Lowland Healthy Adults. High Alt Med Biol 18:1-10
Coffman, Kirsten E; Chase, Steven C; Taylor, Bryan J et al. (2017) The blood transfer conductance for nitric oxide: Infinite vs. finite ?NO. Respir Physiol Neurobiol 241:45-52
Van Iterson, Erik H; Johnson, Bruce D; Borlaug, Barry A et al. (2017) Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure. Eur J Heart Fail 19:1675-1685

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