oxygen delivery and utilization during acute dynamic exercise effects of polycystic ovary syndrome

156 Pages·2017·1.76 MB·English

Department of Sports and Exercise Medicine
Clinicum
Faculty of Medicine
University of Helsinki
Helsinki, Finland

OXYGEN DELIVERY AND UTILIZATION DURING
ACUTE DYNAMIC EXERCISE
EFFECTS OF POLYCYSTIC OVARY SYNDROME, TYPE 1
DIABETES, AND EXERCISE TRAINING

Antti-Pekka Rissanen

ACADEMIC DISSERTATION

To be presented, with the permission of the Faculty of Medicine of the
University of Helsinki, for public examination in Auditorium PIII,
Porthania, City Centre Campus, University of Helsinki,
on May 20th 2017, at 10 o’clock in the morning.

Helsinki 2017
Supervised by Docent Juha Peltonen, Ph.D.
Department of Sports and Exercise Medicine
Clinicum
Faculty of Medicine
University of Helsinki
Helsinki, Finland
Clinic for Sports and Exercise Medicine
Foundation for Sports and Exercise Medicine
Helsinki, Finland
Professor Heikki Tikkanen, M.D., Ph.D.
Institute of Biomedicine
School of Medicine
University of Eastern Finland
Kuopio, Finland
Department of Sports and Exercise Medicine
Clinicum
Faculty of Medicine
University of Helsinki
Helsinki, Finland
Clinic for Sports and Exercise Medicine
Foundation for Sports and Exercise Medicine
Helsinki, Finland
Reviewed by Senior Research Fellow J. Chris Baldi, Ph.D.
Department of Medicine
Dunedin School of Medicine
University of Otago
Dunedin, New Zealand
Docent David E. Laaksonen, M.D., Ph.D., M.P.H.
Internal Medicine
Institute of Clinical Medicine
Kuopio University Hospital
Kuopio, Finland
Opponent Professor Robert Petrella, M.D., Ph.D.
Department of Family Medicine and Kinesiology
Schulich School of Medicine and Dentistry
Western University
London, Canada
Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis
ISBN 978-951-51-3177-5 (paperback) ISSN 2342-3161 (print)
ISBN 978-951-51-3178-2 (PDF) ISSN 2342-317X (online)
Cover artwork: Liia Rissanen
Press: Unigrafia Oy (Yliopistopaino Helsinki), Helsinki, Finland, 2017
http://ethesis.helsinki.fi
Man, he took his time in the sun
Had a dream to understand
A single grain of sand

- from the Nightwish masterpiece
The Greatest Show on Earth
(lyrics by Tuomas Holopainen)
CONTENTS
CONTENTS ..................................................................................................................... 4
LIST OF ORIGINAL PUBLICATIONS ........................................................................... 8
ABBREVIATIONS .......................................................................................................... 9
ABSTRACT ..................................................................................................................... 11
TIIVISTELMÄ (ABSTRACT IN FINNISH) ................................................................... 13

1 INTRODUCTION ......................................................................................................16

2 REVIEW OF THE LITERATURE ............................................................................ 18
2.1 OXYGEN DELIVERY AND UTILIZATION DURING ACUTE DYNAMIC
EXERCISE ......................................................................................................... 18
2.1.1 SYSTEMIC OXYGEN DELIVERY DURING ACUTE DYNAMIC
EXERCISE .................................................................................................. 20
2.1.1.1 Pulmonary function ......................................................................... 20
2.1.1.2 Cardiac pump function .................................................................... 21
Cardiac cycle ................................................................................... 21
Cardiac pump function during acute dynamic exercise .............. 22
Methods to quantify cardiac pump function ................................ 25
2.1.1.3 Blood oxygen carrying capacity ...................................................... 28
2.1.2 PERIPHERAL OXYGEN DELIVERY, EXTRACTION, AND UTILIZATION
DURING ACUTE DYNAMIC EXERCISE .................................................. 29
2.1.2.1 Overview of blood flow distribution and regulation at the whole-
body level ........................................................................................ 29
2.1.2.2 Skeletal muscle blood flow and oxygen extraction and utilization 31
Skeletal muscle blood flow ............................................................. 31
Skeletal muscle oxygen extraction and utilization ....................... 34
2.1.2.3 Cerebral blood flow and oxygen extraction and utilization ........... 35
2.1.2.4 Near-infrared spectroscopy (NIRS) as a method to evaluate tissue-
specific (im)balance between oxygen delivery and utilization ...... 36
2.1.3 PEAK OXYGEN UPTAKE (V̇ O2peak) .......................................................... 40
2.1.3.1 V̇ O2peak as a concept ........................................................................ 40
2.1.3.2 V̇ O2peak as an integrated model ....................................................... 41
2.1.3.3 V̇ O2peak as a predictor of cardiovascular disease and mortality ..... 44
4
2.1.4 EFFECTS OF ENDURANCE TRAINING ON OXYGEN DELIVERY AND
UTILIZATION DURING ACUTE DYNAMIC EXERCISE ......................... 46
2.1.4.1 Effects of endurance training on systemic oxygen delivery ........... 46
2.1.4.2 Effects of endurance training on skeletal muscle blood flow and
oxygen extraction and utilization .................................................. 47
2.1.4.3 Endurance training effects in the context of Fick’s theories ......... 49
2.2 POLYCYSTIC OVARY SYNDROME (PCOS) .................................................... 50
2.2.1 DEFINITION AND EPIDEMIOLOGY ...................................................... 50
2.2.2 PATHOGENESIS ...................................................................................... 50
2.2.3 CLINICAL MANIFESTATIONS ................................................................. 51
2.2.4 PCOS AND EXERCISE ............................................................................. 52
2.2.4.1 Oxygen delivery and utilization during acute dynamic exercise in
PCOS............................................................................................... 52
2.2.4.2 Effects of exercise training in PCOS .............................................. 53
2.3 TYPE 1 DIABETES ............................................................................................ 53
2.3.1 DEFINITION AND EPIDEMIOLOGY ...................................................... 53
2.3.2 PATHOGENESIS ...................................................................................... 54
2.3.3 CLINICAL MANIFESTATIONS ................................................................ 55
2.3.3.1 Microvascular complications ......................................................... 56
2.3.3.2 Macrovascular complications ........................................................ 56
2.3.3.3 Diabetic cardiomyopathy ............................................................... 57
2.3.4 TYPE 1 DIABETES AND EXERCISE ........................................................ 58
2.3.4.1 Oxygen delivery and utilization during acute dynamic exercise in
type 1 diabetes ................................................................................ 58
2.3.4.2 Effects of exercise training in type 1 diabetes .................................61

3 AIMS OF THE STUDY ............................................................................................. 65

4 SUBJECTS AND STUDY DESIGN ........................................................................... 66
4.1 STUDY I ............................................................................................................. 66
4.2 STUDY II ........................................................................................................... 66
4.3 STUDY III .......................................................................................................... 67
4.4 STUDY IV .......................................................................................................... 68
4.5 ETHICAL APPROVAL ....................................................................................... 70

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5 METHODS ................................................................................................................ 71
5.1 CLINICAL EVALUATION AND EXPERIMENTS .............................................. 71
5.1.1 MEDICAL EXAMINATION ........................................................................ 71
5.1.2 PRE-EXERCISE EXPERIMENTS .............................................................. 71
5.1.2.1 Anthropometry ................................................................................. 71
5.1.2.2 Flow-volume spirometry ................................................................. 71
5.1.2.3 Leisure-time physical activity (LTPA)............................................. 71
5.1.3 BLOOD SAMPLES ..................................................................................... 72
5.1.4 BLOOD OXYGEN CARRYING CAPACITY ............................................... 72
5.1.5 CARDIOPULMONARY EXERCISE TEST (CPET) ................................... 73
5.1.5.1 CPET protocols ................................................................................ 73
5.1.5.2 Systemic oxygen delivery ................................................................ 74
Pulmonary function ....................................................................... 74
Cardiac pump function.................................................................. 74
Scaling of cardiopulmonary data ................................................. 75
5.1.5.3 Peripheral oxygen delivery, extraction, and utilization ................. 75
NIRS experiments .......................................................................... 75
Systemic arterial-venous oxygen difference .................................77
5.2 EXERCISE TRAINING INTERVENTION (STUDY IV) ....................................77
5.3 STATISTICAL ANALYSES ................................................................................ 78
5.3.1 STUDY I ..................................................................................................... 78
5.3.2 STUDY II ................................................................................................... 78
5.3.3 STUDY III .................................................................................................. 79
5.3.4 STUDY IV .................................................................................................. 79
5.3.5 STATISTICAL POWER CALCULATION (STUDIES II-IV)...................... 80

6 RESULTS .................................................................................................................. 81
6.1 DESCRIPTIVE CHARACTERISTICS AND BLOOD OXYGEN CARRYING
CAPACITY .......................................................................................................... 81
6.1.1 STUDY I ...................................................................................................... 81
6.1.2 STUDY II .................................................................................................... 81
6.1.3 STUDY III .................................................................................................. 83
6.1.4 STUDY IV ................................................................................................... 83
6.2 OXYGEN DELIVERY AND UTILIZATION DURING ACUTE DYNAMIC
EXERCISE ......................................................................................................... 85
6.2.1 RESPONSES TO CPET IN HEALTHY MEN (STUDY I) .......................... 85
6
6.2.2 RESPONSES TO CPET IN WOMEN WITH VERSUS WITHOUT PCOS
(STUDY II) ................................................................................................. 89
6.2.3 RESPONSES TO CPET IN MEN WITH VERSUS WITHOUT TYPE 1
DIABETES (STUDY III) ............................................................................. 90
6.2.4 EFFECTS OF EXERCISE TRAINING ON RESPONSES TO CPET IN
MEN WITH VERSUS WITHOUT TYPE 1 DIABETES (STUDY IV) ......... 94
6.3 STATISTICAL POWER ..................................................................................... 97

7 DISCUSSION ............................................................................................................ 99
7.1 LOCAL TISSUE-SPECIFIC IMBALANCE BETWEEN OXYGEN DELIVERY
AND UTILIZATION AS PART OF WHOLE-BODY RESPONSE TO ACUTE
DYNAMIC EXERCISE (STUDY I) ..................................................................... 99
7.2 ALTERATIONS IN PERIPHERAL RATHER THAN SYSTEMIC
ADJUSTMENTS TO ACUTE DYNAMIC EXERCISE IN PCOS (STUDY II) .. 102
7.3 BOTH SYSTEMIC AND PERIPHERAL CARDIOVASCULAR IMPAIRMENTS
ARE MANIFESTED DURING ACUTE DYNAMIC EXERCISE IN TYPE 1
DIABETES (STUDY III) .................................................................................. 107
7.4 EFFECTS OF LONG-TERM EXERCISE TRAINING ON RESPONSES TO
ACUTE DYNAMIC EXERCISE AND GLYCEMIC CONTROL IN TYPE 1
DIABETES (STUDY IV) .................................................................................... 111
7.5 METHODOLOGICAL STRENGTHS AND LIMITATIONS ............................. 114

8 SUMMARY AND CONCLUSIONS .......................................................................... 116

9 FUTURE PERSPECTIVES ...................................................................................... 118

ACKNOWLEDGMENTS .............................................................................................. 119
APPENDICES .............................................................................................................. 121
REFERENCES ............................................................................................................ 122
ORIGINAL PUBLICATIONS ....................................................................................... 156

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LIST OF ORIGINAL PUBLICATIONS
This thesis is based on the following original publications:

I Rissanen AP, Tikkanen HO, Koponen AS, Aho JM, Hägglund H, Lindholm
H, Peltonen JE. Alveolar gas exchange and tissue oxygenation during
incremental treadmill exercise, and their associations with blood O2
carrying capacity. Front Physiol. 2012;3:265.

II Rissanen AP, Koskela-Koivisto T, Hägglund H, Koponen AS, Aho JM,
Pöyhönen-Alho M, Tiitinen A, Tikkanen HO, Peltonen JE. Altered
cardiorespiratory response to exercise in overweight and obese women
with polycystic ovary syndrome. Physiol Rep. 2016;4(4):e12719.

III Rissanen AP, Tikkanen HO, Koponen AS, Aho JM, Peltonen JE. Central
and peripheral cardiovascular impairments limit V̇ O2peak in type 1
diabetes. Med Sci Sports Exerc. 2015;47(2):223-230.

IV Rissanen AP, Tikkanen HO, Koponen AS, Aho JM, Peltonen JE. One-year
individualized exercise training intervention enhances cardiorespiratory
fitness but not muscle deoxygenation or glycemic control in adults with
type 1 diabetes. Submitted.

The publications are referred to in the text by their Roman numerals and have been
reprinted with permission of their copyright holders. In addition to the original
publications, some unpublished data are presented.
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ABBREVIATIONS

ANS-EXE Autonomic Nervous System and EXErcise in gestational diabetes
ARTEMIS Innovation to Reduce Cardiovascular Complications of Diabetes at the
Intersection of Discovery, Prevention and Knowledge Exchange
AT anaerobic threshold
ATP adenosine triphosphate
(a-v)O2 arterial-venous oxygen difference
BMI body mass index
BV blood volume
CaO2 arterial oxygen content
C(a-v)O2 systemic arterial-venous oxygen difference
CO carbon monoxide
CO2 carbon dioxide
CPET cardiopulmonary exercise test
CPO cardiac power output
CPOi cardiac power output index
CTI contractility index (= dZ/dtmax)
CvO2 mixed venous oxygen content
CVP central venous pressure
DPF differential pathlength factor
dZ/dt rate of variation of thoracic impedance
dZ/dtmax largest rate of variation of thoracic impedance during systole (= CTI)
EDGE Exercise, Diet and GEnes in T1D
EDV end-diastolic volume
EDVi end-diastolic volume index
EF ejection fraction
EIAH exercise-induced arterial hypoxemia
ES standardized effect size
FEV1 forced expiratory volume in one second
FFM fat-free mass
FinnDiane Finnish Diabetic Nephropathy Study
FVC forced vital capacity
Hb hemoglobin
[Hb] hemoglobin concentration
HbA1c glycosylated hemoglobin A1c
[HbCO] carboxyhemoglobin concentration
HHb deoxygenated hemoglobin
∆[HHb] relative concentration change in deoxygenated hemoglobin
%∆[HHb] normalized relative concentration change in deoxygenated hemoglobin
HOMA-IR homeostasis model assessment of insulin resistance
HR heart rate
IR insulin resistance
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LTPA leisure-time physical activity
MAP mean arterial blood pressure
MET metabolic equivalent (= resting pulmonary oxygen uptake)
NIP near-infrared spectroscopy inflection point
NIPTissueAT/RC NIP observed in (leg muscle, arm muscle, or cerebral) tissue and being
closest to anaerobic threshold or respiratory compensation point
NIRS near-infrared spectroscopy
NO nitric oxide
O2 oxygen
O2Hb oxygenated hemoglobin
∆[O2Hb] relative concentration change in oxygenated hemoglobin
O2 pulse pulmonary oxygen uptake / heart rate
O2 pulsei oxygen pulse index
PaCO2 partial pressure of arterial carbon dioxide
PaO2 partial pressure of arterial oxygen
PCOS polycystic ovary syndrome
PETCO2 end-tidal pressure of carbon dioxide of respired gases
PvO2 partial pressure of muscle venous oxygen
Q̇ cardiac output
Q̇ i cardiac output index
Q̇ VL local microvascular blood flow in the vastus lateralis muscle
RC respiratory compensation point
RER respiratory exchange ratio
SD standard deviation
SHBG sex hormone-binding globulin
SpO2 arterial oxygen saturation
SV stroke volume
SVcal stroke volume during a PhysioFlow calibration procedure
SVi stroke volume index
SVR systemic vascular resistance
SVRi systemic vascular resistance index
tHb total hemoglobin
∆[tHb] relative concentration change in total hemoglobin
tHb-mass total hemoglobin mass
TSI tissue saturation index
V̇ A alveolar ventilation
V̇ CO2 pulmonary carbon dioxide output
V̇ E minute ventilation
V̇ O2 pulmonary oxygen uptake
V̇ O2max maximal pulmonary oxygen uptake
V̇ O2peak peak pulmonary oxygen uptake
WEBWOMEX WEll-Being of WOMen during pregnancy: focus on individualized
EXercise training
Zmax highest thoracic impedance during systole
Zmin lowest thoracic impedance during systole

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