physiological alterations in equine muscle metabolism

188 Pages·2008·7.24 MB·English

Assessment of (patho)physiological alterations in
equine muscle metabolism

Cornélie Martine Westermann
2008
Westermann, Cornélie Martine
Assessment of (patho)physiological alterations in equine muscle metabolism

Dissertation Utrecht University, Faculty of Veterinary Medicine
(with summary in English and Dutch)

ISBN 978-90-393-4754-6

Copyright © C.M. Westermann
Omslag: Lisanne van der Voort, afdeling Multimedia and C.M.Westermann
Lay-out: H. Otter, afdeling Multimedia
Druk: Drukkerij Ridderprint, Ridderkerk

Paranimfen: Annet Spaans en Willem Westermann
Assessment of (patho)physiological alterations in
equine muscle metabolism

Bepaling van (patho)fysiologische veranderingen in het
spiermetabolisme van het paard

(met een samenvatting in het Nederlands)

Proefschrift

ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof. dr. J.C. Stoof,
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen op
donderdag 20 maart 2008
des middags te 2.30 uur

door

Cornélie Martine Westermann

geboren op 7 juli 1968 te Voorschoten
Promotor: Prof. dr. A. Barneveld

Co-promotoren: Dr. J.H. van der Kolk
Dr. L. Dorland

Dit proefschrift werd mede mogelijk gemaakt met financiële steun van de firma Sigma-Tau
te Utrecht, de Universiteitskliniek Paard (Faculteit Diergeneeskunde, Universiteit Utrecht),
Euregio Laboratory Services , Boehringer Ingelheim, Merial BV, Pfizer,
AUV dierenartsencoöperatie, Centropa, IDEXX, Virbac Nederland BV en GD Deventer.
Voor Jerre

Contents

Chapter 1 General introduction 1

Chapter 2 Equine metabolic myopathies with emphasis on the diagnostic
approach; Comparison with human myopathies, a review 9

Chapter 3 Equine biochemical Multiple Acyl-CoA Dehydrogenase Deficiency
(MADD) as a cause of rhabdomyolysis 35

Chapter 4 Acquired Multiple Acyl-CoA Dehydrogenase Deficiency in
10 horses with atypical myopathy 53

Chapter 5 Creatine metabolism, carbohydrate metabolism, purine
metabolism and oxidative phosphorylation in healthy horses and
horses suffering from atypical myopathy 73

Chapter 6 The influence of exercise, training and intensified training on
plasma concentrations of amino acids in Standardbreds 91

Chapter 7 Plasma acylcarnitine and fatty acid profile during exercise
and training in Standardbreds. 107

Chapter 8 The effect of oral tocopherol acetate administration on equine
glucose metabolism, peripheral insulin sensitivity,
and antioxidant status 123

Chapter 9 Discussion 139

Summary 151

Samenvatting 155

Samenvatting voor niet ingewijden 159

Dankwoord 163

Curriculum Vitae 167

List of Publications 169

Coloured illustrations 173

Chapter 1

General introduction
Chapter 1

The horse has had a special place in the life of man for many centuries. Its strength, agility
and ability to learn and trust have contributed to the life of humans by assisting in warfare,
agriculture, business, travel and recreation.
Skeletal muscle is critical for a horse’s mobility. Depending on nutritional status, breed and
build around 44 to 53% of the horse's body weight consists of muscle 1. The muscular
system is closely associated with cardiovascular, pulmonary and endocrine systems, and
disorders of the neuromuscular system have dramatic effects on health and performance of
the horse.
It is therefore of the utmost importance to obtain as much information about the anatomy,
physiology, pathophysiology and diseases of muscle as possible. This thesis aims to make a
contribution to the knowledge base in this area.
In this chapter, muscle metabolism as well as physiological and pathological changes
within muscle will be described. In addition, possible therapeutic options for alterations in
muscle metabolism will be discussed. Finally, the structure and scope of the thesis will be
presented.

Muscle metabolism

Muscle contraction depends on energy provided by adenosine triphosphate (ATP). The
concentration of ATP in the muscle fiber is sufficient to maintain full contraction for only
one to two seconds at most. After this, ATP is split to form adenosine diphosphate (ADP),
which is rephosphorylated to form new ATP within a fraction of a second. There are
several sources of energy for this rephosphorylation (Figure 1) 2.
The first source of energy used is phosphocreatine, which carries a high-energy phosphate
bond similar to the bonds of ATP. The total amount of phosphocreatine in the muscle fibre
is limited, allowing a maximum muscle contraction of five to eight seconds. The reaction is
phosphocreatine + ADP ↔ creatine + ATP 2.
ADP may also be rephosphorylated to ATP through the myokinase reaction, which leads to
increased adenosine monophosphate (AMP) production (2 ADP↔ ATP + AMP). AMP is
deaminated into inosine monophosphate (IMP) and ammonia (NH ). Further deamination
3
leads to purine synthesis 3,4.
The second important source of energy is glycogen. The enzymatic breakdown to glucose
(glycogenolysis) and subsequently to pyruvate (glycolysis) and lactic acid liberates energy
that is used to reconstitute both ATP and phosphocreatine. This glycogenolysis and
glycolysis can occur both in the presence (aerobic) and absence (anaerobic) of oxygen.
Anaerobic glycogenolysis and glycolysis can sustain maximum muscle contraction for
about one minute due to accumulation of its many end products 2.
2