TABLE OF CONTENTS
PART 1: INTRODUCTION
10
1. Cardiac diseases and poor performance of cardiac origin in horses
10
1.1. Cardiac murmurs
10
1.1.1. Innocent murmur
11
1.1.2. Functional murmurs
11
1.1.3. Valvular regurgitation
11
1.1.3.1. Mitral insufficiency
11
1.1.3.2. Aortic insufficiency
12
1.1.3.3. Tricuspid insufficiency
13
1.1.3.4. Pulmonary insufficiency
15
1.1.4. Ventricular Septal Defect
1.2. Rhythm disturbances
1.2.1. Atrial Fibrillation
1.3. Myocardial disease
2. Physical basics of myocardial performance
2.1. Inotropy
15
16
16
17
19
20
2.1.1. Effect of changed inotropy on the pressure-volume diagram
20
2.1.2. Measurement of inotropy
21
2.1.3. Factors regulating inotropy
21
2.2. Preload
22
2.2.1. Effect of changes in preload on the pressure-volume diagram
23
2.2.2. Measurement of preload
23
2.2.3. Factors regulating preload
23
2.3. Afterload
23
2.3.1. Effect of changes in afterload on the pressure-volume diagram
24
2.3.2. Measurement of afterload
25
2.3.3. Factors regulating afterload
25
2.4. Interactions between inotropy, preload and afterload
3. Diagnostic aids in equine cardiology
3.1. Electrocardiography (ECG)
3.1.1. Recording ECG
25
27
27
27
3.1.2. Interpretation of ECG
27
3.1.3. The ECG-derived Heart score
28
3.1.4. Radiotelemetry
29
3.1.5. Long-term ECG monitoring
29
3.2. Radioimaging
30
3.3. Phonocardiography
30
3.4. Biochemical markers of cardiac damage
31
3.5. Blood pressure monitoring
32
3.6. Cardiac Catheterisation
33
3.6.1. Cardiac output measurement by the Fick method
33
3.6.2. Cardiac output measurement by indicator dilution methods
34
3.6.2.1. Cardiac output measurement by dye dilution method
35
3.6.2.2. Cardiac output measurement by thermodilution method
36
3.6.3. Measurement of intracardiac pressures and pressure changes
38
3.6.4. Pulmonary capillary wedge pressure
38
3.6.5. Oxygen tension measurements
39
3.7. Echocardiography
39
3.7.1. Physical basics of diagnostic ultrasound
39
3.7.2. Clinical indications for performing an echocardiogram
42
3.7.3. Evaluation of cardiac structures by B- and M-mode echocardiography
42
3.7.3.1. Evaluation of the cardiac chambers and walls
43
3.7.3.2. Evaluation of cardiac valves
43
3.7.3.3. Evaluation of the pericardium
44
3.7.4. Evaluation of cardiac function by B- and M-mode echocardiography
44
3.7.4.1. Indices of systolic cardiac function
44
3.7.4.2. Indices of global cardiac function
45
3.7.5. Evaluation of cardiac function by Doppler echocardiography
46
3.7.5.1. Evaluation of transvalvular flows
47
3.7.5.2. Measurement of diastolic cardiac function by Doppler
47
echocardiography
3.7.5.3. Doppler-derived pressure gradients
48
3.7.5.4. Evaluation of cardiac function by Doppler echocardiography
48
3.7.6. Contrast echocardiography
50
3.7.7. Echocardiographic heart score
50
3.7.8. Doppler tissue imaging
51
3.7.9. Exercise stress echocardiography
51
4. Stress echocardiography in humans
53
4.1. Indications of stress echocardiography
53
4.2. Pathophysiology of ischemic disease detected by stress echocardiography
53
4.3. Ischemic stressors in stress echocardiography
53
4.3.1. Treadmill exercise stress test
54
4.3.2. Bicycle exercise stress test
54
4.3.3. Dobutamine stress test
54
4.3.4. Dipiridamole stress test
55
4.3.5. Electrical Pacing stress test
55
4.4. The stress test protocol
55
4.5. Interpretation of stress echocardiography
56
4.6. Accuracy of stress echocardiography for the detection of coronary artery disease
56
5. Dobutamine and atropine as modifying agents of cardiac function
5.1. Dobutamine
58
58
5.1.1. Pharmacology and pharmacokinetics of dobutamine
58
5.1.2. Mechanism of action of dobutamine
58
5.1.3. Chronotropic effect of dobutamine
59
5.1.4. Dromotropic effect of dobutamine
60
5.1.5. Lusitropic effect of dobutamine
60
5.1.6. Therapeutic use of dobutamine in human and veterinary medicine
60
5.2. Atropine
61
5.2.1. Pharmacokinetics of atropine
61
5.2.2. Atropine’s action on the heart
62
5.2.3. Atropine’s action on other organs
62
5.2.4. Therapeutic use of atropine in human and veterinary medicine
62
5.3. Combined effects of atropine and dobutamine
63
PART 2: RESEARCH OBJECTIVES
65
PART 3: SYNOPSIS OF EXPERIMENTS
67
1. Comparison of the effects of high-dose dobutamine and atropine/low-dose
67
dobutamine on cardiac output as an indicator of global left ventricular function
(Study 1)
2. Effect of atropine/low-dose dobutamine stress test on left ventricular
73
echocardiographic B- and M- mode parameters in healthy horses (Study 2)
3. Comparison of exercise to pharmacological stress echocardiography in
78
healthy horses (Study 3)
4. Effect of atropine/low-dose dobutamine stress test on major determinants
84
of myocardial performance in healthy horses (Study 4)
5. Cardiac power output measurement using a dobutamine stress test in
90
healthy horses (Study 5)
PART 4: GENERAL DISCUSSION, CONCLUSIONS, PERSPECTIVES
95
PART 5: REFERENCES
100
PART 6: SCIENTIFIC PAPERS
130
1. Atropine reduces dobutamine-induced side effects in ponies
131
undergoing a pharmacological stress protocol
Sandersen C., Detilleux J., Delguste C., Pierard P., van Loon G., Amory H.
Equine Vet. J., 2005, 37, 128-132.
2. Effect of Atropine-Dobutamine Stress Test on Left Ventricular
145
Echocardiographic Parameters in Untrained Warmblood Horses
Sandersen C.F., Detilleux J., de Moffarts B., van Loon G., Amory H.
Journal of Veterinary Internal Medicine 2006, 20, 575-580.
3. Exercise and pharmacological stress echocardiography in healthy horses
Sandersen C., Detilleux J., Art T., Amory H.
Equine Exercise Physiology 7 (Equine Vet. J. Suppl.), 2006, 36, 159-162.
159
4. Afterload and contractility during dobutamine stress test in healthy horses
172
Sandersen C., Detilleux J., Amory H.
In preparation
5. Cardiac power output during dobutamine stress test in healthy horses
186
Sandersen C., McEntee K., Detilleux J., Amory H.
Submitted for publication
6. Stress echocardiography in horses – a review
203
Sandersen C. and Amory H.
Pferdeheilkunde 2006, 22, 609-617.
PART 7: SUMMARY
224
PART 8: RÉSUMÉ
229
PART 9: INDEX OF ABBREVIATIONS
236