Myocardial degeneration

Cardiac muscle is structurally similar to skeletal muscle and

is subject to the same anatomic types of degeneration. There
is, however, a greater liability for cardiac muscle to undergo
degeneration as a response to many nonspecific causes, probably
related to its continuous activity.
Diffuse nonspecific myocardial
degeneration occurs secondarily in a variety of systemic
diseases, especially infectious fevers, anemia, and toxemia.
Hydropic change, or vacuolar degeneration, of the myocardium
is characterized grossly by a dull gray appearance and
increased friability so that the myocardium is easily torn. On
cut surface, the muscle is smoother than normal, the outlines
of individual muscle bundles obscured.
Fatty change—the appearance of lipid vacuoles in myocyte
cytoplasm—is a more severe event than hydropic change, and
may be recognized grossly as uneven patches of pale yellow
myocardium. The process of fatty change is not uniform, and
it is sometimes possible to recognize, beneath the endocardium,
alternating bundles of fibers or strips of myocardium
more yellow than the remainder (“thrush-breast heart”). Both
hydropic change and fatty change are reversible forms of cellular
injury.
Atrophy of the heart occurs in chronic wasting diseases and
malnutrition. In some cases, the atrophy is accompanied by
dark pigmentation, and it is then called “brown atrophy.” It
should be recognized, however, that atrophy can occur without
pigmentation, and pigmentation can occur without atrophy.
Ruminants are principally affected by atrophy, brown or not,
and rarely does the atrophic heart produce clinical disturbance.
The epicardial fat may be gelatinous, the endocardium
wrinkled, and myocardium brown and friable. Histologically,
the muscle fibers are thin, the nuclei small and dark, and
masses of brown pigment granules are present within secondary
lysosomes at the nuclear poles. The pigment is lipofuscin
(“wear-and-tear pigment”), an oxidation product of unsaturated
lipids.
Xanthosis (xanthomatosis) refers to the abnormal lipofuscin
pigmentation of the myocardium and skeletal muscles seen in
cattle, particularly mature Ayrshire cows (see Vol. 1, Muscle
and tendon). Microscopically, lipofuscin is commonly seen at
the nuclear poles of cardiac myocytes in aged dogs and cats.
Mineralization occurs quite commonly in the myocardium,
and is to be expected whenever there is necrosis of fibers.
Calcium salts are selectively deposited in the Purkinje network
in organomercurial poisoning in cattle, in which the mineralization
is preceded by hyaline necrosis of the Purkinje fibers
and is followed by surrounding fibrosis.
Osteocartilaginous metaplasia of the right atrial myocardium
in sheep is a common incidental finding in adults, and
has been reported at a prevalence of ~10%. The foci of metaplasia
are often palpable grossly, but may only be detectable
by radiography or microscopy. Histologically, the myocardium
of the atrial free wall contains trabeculae of lamellar bone that
are bordered by cartilage and chondroid matrix (Fig. 1-36).
The metaplastic regions are not associated with the os cordis
at the heart base.

Myocardial necrosis*
Focal to massive myocardial necrosis, or residual scars thereof,
is a common lesion in postmortem material. The causes are quite varied and part of a number of disease
syndromes
described elsewhere in these volumes.
In infectious disease, the distinction between myocardial
necrosis and myocarditis with myofiber necrosis is somewhat
arbitrary—inflammatory cells will invade necrotic myocardium;
in acute myocarditis, inflammatory cells should be intimately
associated with necrotic myocardial cells, and adjacent
myocytes may appear normal. Necrosis predominates in
highly fatal foot-and-mouth disease in neonatal lambs, piglets,
and calves, whereas the residual lesions in older cattle qualify
as myocarditis with a significant inflammatory response. Fulminating
infection by canine distemper virus in young puppies
is purely degenerative, whereas parvoviral and herpesviral
infections in the same age group contain elements of an
inflammatory response. Of the bacterial diseases, and excepting
blackleg, Histophilus somni appears to be responsible for a
residual syndrome of sudden death in cattle with myocardial
necrosis or infarction, although in some cases myocardial
abscesses may be present.
Severe, often fatal, myocardial necrosis is typically part of
the important vitamin E and selenium-responsive syndromes
of nutritional myopathy of lambs, calves (Fig. 1-37A, B),
swine, and horses, and in mulberry heart disease of swine.
It may also be seen as part of equine rhabdomyolysis and
of capture myopathy and other exertional syndromes (see
Vol. 1, Muscle and tendon).
Deficiency disease, additional to those that respond to
vitamin E and selenium, may include myocardial necrosis. It
occurs, although not invariably, in thiamine deficiency in carnivores,
always as a single acute episode. Falling disease of
cattle in Australia and Florida is a syndrome of sudden death
believed to result from prolonged copper deficiency. Myocardial
scars accompany acute lesions, suggesting repetitive episodes
and resembling the lesions of fluoroacetate poisoning in
cattle eating the gidgee plant, Acacia georginae, which is to be
distinguished from the nontoxic Acacia cambadgei (gidyea,
gidgee). In cats, taurine deficiency causes myocardial failure.
Toxic myocardial degeneration is common, and although
some examples are accompanied by degeneration of skeletal
muscle, they are described here. Injectable saccharated iron
compounds, by virtue of the capacity of iron to generate free
radicals in ferric/ferrous translations, cause fatal myocardial necrosis in piglets. Monensin, an ionophore
that is widely used
as a coccidiostat and growth promotant in ruminants, may
contaminate compounded feeds for simple-stomached animals
and is cardiotoxic for horses and pigs (see Vol. 1, Muscle and
tendon for details of poisoning in other species). Also, ruminants
fed dried poultry litter containing the ionophores.

Plants that contain cardiac glycosides of both the bufadienolide

and cardenolide types are of worldwide distribution.
Poisoning by bufadienolide cardiac glycoside–containing
plants is the most important plant-associated poisoning of
livestock in southern Africa, and may be acute or chronic.
Acute poisoning is caused by plants of the family Iridaceae
(“tulip”), for instance, Homeria pallida (the cape tulip), H.
miniata, Moraea polystachya, M. bipartita; family Liliaceae
(“slangkop”), for instance, Urginea sanguinea; and family Santalaceae,
for instance, Thesium lineatum (“witstorm”). As well,
several species of Bryophyllum (synonym Kalanchoe) that
occur in Madagascar and have been introduced to southern
and eastern Africa, and Australia, for instance, B. tubiflorum
and B. pinnatum, contain bufadienolides (bryotoxins A, B, C,
or bryophyllins).
In acute poisoning, death occurs within a few hours of
ingesting the plant. Affected animals have cardiovascular
(tachycardia, arrhythmia, heart block), gastrointestinal, respiratory,
and neuromuscular signs. Some cases may live for a few
days and have scattered foci of myocardial necrosis, but usually
a diagnosis must be based on demonstrated access to the plant,
the observed clinical syndrome, and the presence of recognizable
plant parts in the ingesta. The cardiac glycosides are
inhibitors of the sodium-potassium ATPase pump, which is
responsible for maintaining membrane ion concentrations and
the membrane potential of cardiac muscle fibers.

The gross and microscopic appearance of myocardial

necrosis is dependent on the interval between the initial insult
and death. Gross changes of necrosis are not readily apparent
until 12 hours after injury. By 18 to 24 hours, the affected
area, in which calcium salts may be deposited, is paler and
gray-brown (Fig. 1-39). The overlying serous membrane is
usually normal. Myocardial degeneration, mineralization, and
necrosis are most common in the subendocardial myocardium.
This area undergoes the greatest intramyocardial tension
during systole and is the most likely to be ischemic. However,
proliferative or thrombotic lesions completely occluding
vessels in these areas are rarely observed even with careful
technique. The common small foci of myocardial necrosis may
not be visible from the serous surface, and perhaps may be
recognizable only microscopically. The necrosis resulting
from infarction will, if sufficiently large, involve the serosal
surfaces and produce fibrinohemorrhagic thickening of the
pericardium that may neatly overlie and indicate the infarcted area. In cases dying within 24 hours, the
pericardial reaction
may be the only indication grossly of infarction, the necrotic
muscle at this stage not being clearly altered or merely pale.
The necrotic area becomes more sharply defined by hyperemia
by the second to fourth days. By the tenth day, there is
beginning replacement of the necrotic zone by fibrous
ingrowth. Replacement fibrosis is well established by the end
of the sixth week. A substantial, often transmural loss of myocardium
and replacement by fibrous tissue may lead to the
development of aneurysms of the ventricular wall.
Microscopically, lesions are not usually detectable for the
first 6-12 hours. However, ultrastructural changes are observed
within 1 hour. Recognition as early as 2 hours may be possible
using special stains, such as hematoxylin-basic fuchsin-picric
acid. Necrosis becomes apparent by routine stains after 12
hours (Figs. 1-40, 1-41). Subsequently, neutrophils infiltrate the affected area, and the nuclei of the
myocytes become
pyknotic. At this stage, macrophages are evident. Granulation
tissue appears at the periphery of the lesion toward the end
of the first week and usually predominates by the end of the
sixth week.
There are variations in the microscopic appearance of
myocyte necrosis, and some attempt has been made to associate
the differing microscopic patterns with particular causes,
but these associations are not definitive. The first variant is
coagulative necrosis characterized by cellular swelling, nuclear
hyperchromasia, early loss of striations, and a “granular”
appearance of the myocyte. This type of change is observed
primarily in ischemic states. Coagulative myocytolysis is typified
by the presence of thick, irregular, eosinophilic bands,
with an accompanying loss of striations and lightly staining
granular areas in myocytes. The bands are hypercontracted
sarcomeres (“contraction bands”) (see Fig. 1-41) and the light
granular areas are mitochondria. Evidence from experimental
models suggests that the alteration is the result of the excessive
release of endogenous catecholamines. However, this change
may be observed in normal myocardium if it is fixed immediately
after death. Colliquative myocytolysis appears as a loss
of striations, and homogeneous, weakly eosinophilic cytoplasm.
The ultrastructural appearance is characterized by
intracellular edema, with disintegration of fibrils and other
organelles. Waviness of myocardial fibers is claimed by some to
be one of the earliest changes observed in myocardial infarction
in humans. The affected fibers are not necrotic, but are
thinner and undulating in appearance. It is thought that the
waviness is due to irreversible stretching followed by compression
of ischemic fibers by the surrounding viable myocardium.
Attenuated wavy fibers (<6 μm diameter, wavy appearance)
have been noted to be common in the myocardium of dogs
with dilated cardiomyopathy.
Anichkov (Anitschkow) cells, also known as “caterpillar
cells,” have been observed in myocarditis and a variety of naturally
occurring and experimentally induced myocardial necroses.
They are also seen in rheumatic fever in humans in
association with Aschoff bodies. Anichkov cells appear as large
mononuclear cells in which the nuclear chromatin is present
in an undulating wavy ribbon with slender processes radiating
from it (Fig. 1-42). The origin of these cells is in dispute. Suggestions
include a fibroblastic, pericytic, endothelial, or myocytic
origin. Depending on the theory accepted, the function
is either that of a macrophage or an abortive attempt at
cardiac myocyte regeneration.
A few of the more interesting examples of myocardial
degeneration and necrosis follow.