Track topics on Twitter Track topics that are important to you
The purpose of this study is to examine the effect of dopamine infusion and dopamine-2 receptor blockade on pulmonary capillary blood volume, diffusion, and the hemodynamic variables of pulmonary artery pressure, cardiac output, and pulmonary vascular resistance during exercise. Secondarily, this study will examine the effect of dopamine infusion and dopamine-2 receptor blockade on exercise tolerance.
1. Study Objectives
The primary objective of this study is to examine the effect of dopamine infusion and dopamine-2 receptor blockade on pulmonary capillary blood volume, diffusion, and the hemodynamic variables of pulmonary artery pressure, cardiac output, and pulmonary vascular resistance during exercise. Secondarily, this study will examine the effect of dopamine infusion and dopamine-2 receptor blockade on exercise tolerance.
To meet the increased oxygen demand required for exercise, pulmonary diffusing capacity (DLCO) must increase in order to avoid a drop in arterial oxygenation and early exercise termination. Enhanced DLCO during exercise is achieved by expanding pulmonary capillary blood volume (Vc) and diffusing membrane capacity (Dm) through recruitment and distention of the pulmonary capillaries, effectively increasing the surface area for diffusion. Recruitment and distention of the pulmonary capillaries decreases pulmonary vascular resistance (PVR), increasing pulmonary blood flow (Q) while limiting the rise in pulmonary artery pressure (PAP) with exercise.
In health, pharmacological interventions are not believed to affect PAP during exercise. However, dopamine, a pulmonary vasodilator, may help to regulate PAP during exercise. Specifically, dopamine appears important for a normal cardiovascular exercise response, as Metoclopramide (pulmonary dopamine-2-receptor antagonist) decreases maximal Q and exercise tolerance (1). These results suggest that dopamine may modulate Vc during exercise via pulmonary smooth muscle regulation, subsequently affecting PVR, PAP, Q and exercise tolerance. However, how dopamine regulates DLCO, Vc, Q, and exercise tolerance is unknown.
Purpose: The purpose of this study is to examine the effect of a dopamine agonist and a dopamine-2-receptor antagonist on DLCO, Vc, PAP, PVR, Q, and exercise tolerance.
Hypothesis: It is hypothesized that dopamine will increase Vc, leading to a reduction in PVR and a corresponding decrease in PAP. This response will allow an increase in DLCO, Q, and exercise tolerance relative to control. Conversely, Metoclopramide (dopamine-2-receptor antagonist) will attenuate the increase in Vc as well as the reduction in PVR, leading to an increase in PAP. In this condition, DLCO, Q, and exercise tolerance will be reduced.
Study Overview: This study will utilize a randomized, double-blind crossover design where healthy subjects will have measurements performed at rest and 2 workloads (60% and 85% of previously determined VO2peak) with either intravenous dopamine (2µg/kg/min), dopamine receptor blockade (20mg oral Metoclopramide), or placebo (order randomized). Data will be collected across 5 different days over a 2-3 week period. Day 1: Pulmonary function and graded exercise testing to exhaustion. Day 2-4: Vc determination at rest and exercise with either intravenous dopamine, dopamine receptor blockade, or placebo (order randomized). Following a brief period of rest, time to exhaustion trials at 85% of VO2peak will be performed to characterize exercise tolerance. Day 5: Evaluation of PAP via cardiac ultrasound at rest and during exercise with either intravenous dopamine, dopamine receptor blockade, or placebo (order randomized).
Pulmonary Function & Cardiopulmonary Exercise Test: Subjects will undergo a graded exercise test to volitional exhaustion to characterize aerobic fitness (VO2peak) and a standard pulmonary function test to characterize lung function parameters.
DLCO and Vc measurement during exercise: DLCO and Vc will be measured using the multiple oxygen tension DLCO breath-hold method (2) at rest and during cycling exercise at 60% and 85% of VO2peak. Over different three days, participants will be randomized to each of the following conditions: 1) dopamine (2 μg/kg/min intravenous) and a placebo pill, 2) metoclopramide (20 mg oral) and intravenous saline, or 3) intravenous saline and a placebo pill. During each workload, subjects will perform a DLCO breath-hold maneuver for six seconds, repeated three times during exercise at differing oxygen tensions (0.21, 0.40, 0.60; workload and oxygen tension randomized) allowing for calculation of Vc and Dm. Trials will be spread over several days to ensure no CO buildup. DLCO will be corrected for hemoglobin, and we have considerable experience in performing these tests.
Pulmonary Artery Systolic Pressure (PASP), PVR, and Q: Doppler echocardiography (PASP) will be used as a non-invasive estimate of PAP in all dopamine conditions. PASP will be evaluated at rest and during exercise, and this method has been used successfully by our group and others in previous investigations(3,4). Total PVR will be evaluated by dividing PASP by Q at any given workload. Q will be evaluated using the Physioflow® Impedance Cardiography (Manatec® Biomedical). When compared to direct Fick methods, impedance cardiography provides an accurate determination of Q at rest and during exercise.
Hemoglobin: Since DLCO will be corrected for hemoglobin concentration, a small sample of blood will be collected via finger prick at rest and during exercise and analyzed for hemoglobin concentration using a hand-held Hemoglobin measurement device (HemoCue 201+, HemoCue AB, Angelholm, Sweden).
Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Basic Science
Dopamine, Metoclopramide, Placebos, Rest, Exercise - 60%, Exercise - 85%
Clinical Physiology Research Laboratory
Not yet recruiting
University of Alberta
Published on BioPortfolio: 2016-11-18T12:53:22-0500
Metoclopramide is a dopamine antagonist frequently used for the treatment of nausea, vomiting, and migraine headaches in Emergency Departments (EDs). However, little research has focused o...
Uremic etiology Restless legs syndrome (RLS) has been associated with poorer quality of life (QoL) compared to RLS-free counterparts mainly due to sleep deprivation factors. Exercise train...
Parkinson's disease is caused by a reduction of dopamine causing motor deficits. The investigators are studying how exercise can help PD patients by increasing dopamine release in an area ...
Pulmonary hypertension (PH) at rest is a risk factor for death in patients with sickle-cell anemia (SCA). Exercise echocardiography (EE) can detect latent PH. We sought to investigate the ...
The purpose of this research study is to understand how different kinds of exercise affect the human body and the health of the heart and lungs. For example, some people like to exercise c...
Cognitive function is reported to improve by moderate aerobic exercise. However, the effects of intermittent exercise with rest between the moderate-intensity exercise are unclear. Therefore, this stu...
Measurement of oxyhemoglobin (OHb) changes in the cerebral cortex using near-infrared spectroscopy (NIRS) shows that its levels increase during moderate-intensity exercise and persists after exercise....
The aim of the present study was to evaluate the differences in salivary proteome at rest and in response to an acute exercise in men and women. For this, unstimulated whole saliva samples in rest and...
During a traditional set configuration of resistance exercise (TRD), characterized by a continuous completion of repetitions, a decrease in power output tends to occur throughout a set of repetitions....
An elevation in cardiac troponin T (cTnT), as a highly specific biomarker of cardiomyocyte damage, after moderate-intensity continuous exercise (MCE) has been described. The exercise-induced cTnT resp...
Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate.
The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an EXERCISE TEST.
Tapering-off physical activity from vigorous to light, to gradually return the body to pre-exercise condition and metabolic state.
Asthma attacks following a period of exercise. Usually the induced attack is short-lived and regresses spontaneously. The magnitude of postexertional airway obstruction is strongly influenced by the environment in which exercise is performed (i.e. inhalation of cold air during physical exertion markedly augments the severity of the airway obstruction; conversely, warm humid air blunts or abolishes it).
Alternating sets of exercise that work out different muscle groups and that also alternate between aerobic and anaerobic exercises, which, when combined together, offer an overall program to improve strength, stamina, balance, or functioning.
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Vascular relates to blood vessels (Oxford Medical Dictionary) and can be used to describe the supply of blood, a disease affecting the blood vessels or molecules associated with these structures. For example, <!--LGfEGNT2Lhm-->atherosclerosis ...