Download Polyunsaturated fatty acids in canine heart disease

Polyunsaturated fatty acids
in canine heart disease
Executive summary: omega-3
in heart health in dogs
Ten percent of the dog population are currently estimated to
be affected by heart disease; ninety percent of which suffer
from mitral valve disease (MVD) or dilated cardiomyopathy
(DCM); both incurable and progressive diseases.
From the onset of both these conditions, there is a long
“preclinical” phase, during which the dogs have no clinical
signs of heart failure and appear to be healthy. During this
phase dogs of certain breeds have an increased risk of
cardiac arrhythmia.
Adaptive mechanisms in the vascular system and the heart
compensate for the reduction in cardiac output. These
compensatory mechanisms lead to cardiac remodeling and
may contribute to the worsening of cardiac function. Human
studies have indicated that inflammation and changes in
myocyte metabolism may play an important role in this part of
disease progression.
As there are no pharmaceutical drugs shown to be effective
during this phase, the vets may try to support the heart by
suggesting dietary changes and excercise.
In humans, there is good evidence that two of the omega-3
fatty acids, eicosapentanoic acid (EPA) and Docosahexaenoic
acid (DHA), can help support heart health. In dogs, there is
also some evidence that EPA and DHA, can help support
heart health. Mechanisms through which EPA and DHA
are believed to be of benefit involve reduction
of inflammation, support of myocyte metabolism and cell membrane stabilisation.
Cardiac disease in dogs
Dilated Cardiomyopathy (DCM)
Ten percent of dogs in the general population are estimated
to have heart disease. This is expected to rise as longevity is
increasing; with obese dogs and certain breeds being
particularly at risk.1
DCM is characterised by a gradual weakening and elongation
of the heart muscle cells. These changes cause gradual
dysfunction of the myocardium leading to a progressive
failure of the heart to pump blood efficiently. As in MVD, the
decrease in pump function leads to a stimulus of the
sympathetic nervous system and chronic activation of the
sympathetic nervous system followed by a gradual
enlargement of the heart.2
Of the affected population of dogs with heart disease,
ninety percent are diagnosed as either having mitral valve
disease (MVD) or dilated cardiomyopathy (DCM).1,2 Both
diseases are chronic and progressive with no curative
treatment at present.2
Mitral Valve Disease (MVD)
MVD is a disease characterised by an initial denudation of the
endothelium on the mitral valves leading to incompetence of
valves due to a gradual thickening caused by a build up of
collagenous material.3 In this environment, genes involved in
the inflammatory response are upregulated indicating that
there may be an inflammatory component to valve
deterioration.4 This is supported by recent research which has
demonstrated an increased level of inflammatory mediators.5
As the valves become incompetent the decreased output
from the heart leads to stimulation of the sympathetic nervous
system, which increases the heart rate and contractility, and
increases water retention in the kidneys to expand plasma
volume.2 Over a period of time the compensatory mechanisms
contribute to a gradual enlargement of the heart; recognised
macroscopically as cardiac remodeling.2
The compensatory mechanisms may allow the patient to
remain free of clinical symptoms and is therefore unpredictable.2
The time from diagnosis of disease to development of clinical
signs of the disease is often several years.6 These signs appear
when the compensatory mechanisms are no longer able to
maintain proper blood circulation.2
Dogs with DCM can remain free of clinical signs of disease for
many years. But it has been shown that in certain breeds,
some dogs have an increased risk of sudden death due to
cardiac arrhythmia.7
Once the DCM dog has clinical symptoms of the disease,
disease progression is rapid and some studies have shown
that more than half of dogs die within the first year after onset
of clinical symptoms.8
Role of inflammation in
decompensated cardiac disease
What are polyunsaturated
fatty acids?
Inflammation is believed to be a significant factor in
progression of human chronic heart failure.9 This inflammation
is characterised by an increase in pro-inflammatory cytokines
such as TNFα, IL1 and IL6, believed to be produced by cells
such as myocytes in response to cellular stimulation (including
cell damage).9 In experimental models of heart failure,
increased activation of TNFα, has been linked to increased
inflammation, decreased contractility of cardiac tissue and
increased rate of remodeling.10 Elevated levels of proinflammatory cytokines have been found to be associated
with an increased risk of cachexia.11
Polyunsaturated fatty acids (PUFAs) are essential elements of the
cell membrane important for regulation of cellular function.
There are not many studies investigating effect of
inflammation in dogs with heart disease, however one study
found a negative correlation between the levels of proinflammatory cytokine IL1 and survival time.12
In the normal heart, myocytes efficiently metabolise fatty acids
to meet their energy requirements.2 In the heart affected by
chronic heart failure, myocytes are believed to undergo
complex changes in the metabolic pathways, which reduce
their ability to produce energy efficiently.11 Such changes have
been found to be associated with myocyte damage and
increased apoptosis and there is some evidence that this may
play a role in the remodeling process of the heart.13
Thus, there is a growing body of evidence that reducing
inflammation could therefore be an important step in
maintaining heart health.
The two types most often mentioned in relation to health are:
• Omega-3 fatty acids
• Omega-6 fatty acids
Of these PUFAs, increased intake of two omega-3 types,
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
has been found to be related to reduction in incidence of
cardiovascular events in humans14 and to an increase in
survival in dogs with heart failure.15
Dietary sources of EPA and DHA
Mammals are not able to synthesise the omega-3 PUFAs
and they therefore depend upon a sufficient consumption
of these fatty acids from the diet in order to meet their
physiological requirements.16
The concentrations of the omega-3 PUFAs EPA and DHA in the
human and dog diet are usually very low. Diets that are low in
EPA and DHA can be improved by supplementation.
Replacement of AA by EPA/DHA
EPA/DHA
AA
Increasing the amount of EPA and DHA in the diet
increases their concentration in the cell membrane
as they readily displace the omega-6 fatty acid
arachidonic acid (AA)
Effects of EPA and DHA
in heart health
In humans, there is good evidence that two of the omega-3
fatty acids, EPA and DHA, can help support heart health.14 This
evidence has been implemented in guidelines for
management of heart health in humans to the extent that
daily omega-3 supplementation is now recommended.
There are indications that the observed reduction in the
incidence of cardiovascular events in humans may be the
sum of many effects of EPA and DHA, some of which might
also be relevant in canine heart disease. These include the
ability to reduce the production of pro-inflammatory
cytokines, TNFα and IL1 in patients with heart failure,17 the
ability to modulate the excitability of myocytes through the
direct interactions with membrane ion channels and the
ability to attenuate pressure overload-induced remodeling,
and contractile dysfunction.19
Reduction of inflammation
When myocytes are damaged the fatty acids in the cell
membrane are released as precursors for inflammatory
mediators. The type of inflammatory mediator which is
produced depends upon the type of fatty acids from which
it originates.
Those inflammatory mediators which are produced from EPA
and DHA are less inflammatory than those mediators, which
are produced from other types of fatty acids. This is supported
by studies that demonstrate that increasing the dietary intake
of EPA and DHA may reduce the concentration of proinflammatory mediators.12,20
Heart cells (Myocytes)
EPA and DHA
Other fatty acid
Cell injury
No supplementation with EPA/DHA
Supplementation with EPA/DHA
Each myocardial cell membrane
is made up of thousands of fatty
acids
When the cell is injured, signaling
increases. The type of response to
the signal will depend on the ratio
of the different types of fatty acid
Release of
inflammatory mediators
Release of less
inflammatory mediators
Initiates and drives
inflammation
No increase
of inflammation
Increases rate of cardiac
disease progression
Does not contribute to further
disease progression
Other supportive effects of EPA
and DHA supplementation in
heart disease
Support of myocyte metabolism
EPA and DHA are believed to support myocyte metabolic
efficiency through up-regulation of the expression of lipid
metabolism genes.19 Increased intake of EPA and DHA has
been associated with decreased cachexia score and increased
survival in two studies in dogs with heart failure.15
Decreasing risk of arrhythmia
In dogs, EPA and DHA have been linked to decrease of
ventricular fibrillation after induced cardiac arrhythmia in
experimental models22 and to reduction of arrhythmia in
boxer dogs with arrhythmogenic right ventricular
cardiomyopathy in a clinical study.23
Support of canine heart health with EPA and DHA
There are currently no pharmaceutical drugs that have been
proven to be beneficial in the preclinical phase of heart
disease. Therefore, vets may support the heart during this
phase by suggesting dietary changes and exercise. There is
some documentation that increasing EPA and DHA intake in
dogs with heart disease may support compromised hearts.
Supplementing dogs with heart disease with EPA and DHA
may be one of the management options for support of
heart health.
Tryck Bohlins 2010-05
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Boehringer Ingelheim Vetmedica
DK Strødamvej 52, 2100 Køpenhamn Ø, +45 39 15 88 88
S
Box 467, 201 24 Malmö, +46 40 23 34 00
N Postboks 155, 1376 Billingstad, +47 66 85 05 70
www.bivet-ca.nu
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