Page 380 - Feline Cardiology

398 Section N: Endocrine Diseases Affecting the Heart

ventricular concentric hypertrophy, including systemic Hyperthyroid patients of many species commonly
hypertension, increased erythropoietin release, activa- have sinus tachycardia (Klein and Ojamaa 2001; Peterson
tion of the renin-angiotensin-aldosterone system, and 1982; Feldman and Nelson 2004). There are several factors
chronic sympathetic stimulation (Kittleson and Kienle that contribute to increases in heart rate and potentially
1998; Klein and Ojamaa 2001). to arrhythmogenesis in hyperthyroidism, including a
Increased systolic and diastolic function are the result greater density of beta-adrenergic receptors as noted
of several factors. An increase in myosin ATPase activity above, increased peripheral tissue demand, increased
occurs due to the binding of T3 to the α-myosin heavy myocardial oxygen consumption as found in cats with
chain (V1) gene’s regulatory region. Greater α-myosin experimentally induced hyperthyroidism (Skelton et al.
heavy chain (V1) activity increases systolic function 1970), atrial and ventricular enlargement, and actions on
because myosin ATPase serves the essential function of several membrane pumps and channels (see Figure 26.1).
hydrolysis of ATP to ADP and Pi, generating energy in
the process that fuels the power stroke of actin-myosin Causes of Hyperthyroidism
interaction (Opie 2004). Triiodothyronine also increases Although a causative relationship has not yet been
influx of calcium into the myocyte cytosol through proven between specific etiologies and naturally occur-
L-type sarcolemmal calcium channels and ryanodine ring feline hyperthyroidism, associations with goitro-
channels in the sarcoplasmic reticulum, both of genic substances have been found through epidemiologic
which are T3-responsive, and this increase in cytosolic investigations. One exhaustive environmental study
calcium increases inotropic function. Venoconstriction identified a threefold increase in risk of hyperthyroidism
is observed in hyperthyroidism, increasing return of in cats that used litter compared to those that did not.
blood to the heart and raising stroke volume according A proposed explanation is that litter-using cats tend to
to Starling’s law (Dillman 2002). An increase in beta- be indoor cats, and a previous study identified an elev-
adrenergic receptor density identified in hyperthyroid enfold greater risk of hyperthyroidism in indoor cats
hearts also can be expected to contribute to increased compared to outdoor cats (Scarlett et al. 1988), and thus
systolic function (Dillman 2002). Diastolic function is either are exposed to hyperthyroid-inducing substances
enhanced via T3-mediated phosphorylation (disinhibi- or simply are more closely cared for and thus more likely
tion) of phospholamban, the protein that otherwise to live to the age at which hyperthyroidism occurs and
blocks sarcoplasmic reticulum calcium ATPase (SERCa2, to have owners take note of clinical signs and seek vet-
the pump that evacuates intracytoplasmic calcium and erinary care.
thus initiates diastole) (Dillman 2002; Klein and Ojamaa For over 2 decades, the consumption of canned food
2001). Finally, T3 alters the function of various cardiac has been associated with a higher risk of hyperthyroid-
sodium and potassium channels, an interplay that con- ism in cats. Scarlett et al. (1988) and Feldman and
tributes to inotropy and lusitropy (see Figure 26.1). Nelson (2004) point out that the appearance of com-
These systolic and diastolic effects are mediated by T3 mercial canned cat food in North America the late 1960s
directly and not via the autonomic nervous system, as coincides with the emergence of hyperthyroidism in cats
Endocrine Diseases tolic or diastolic function, when a beta-blocking drug is sumed such food for several years would have begun to
beginning some 10 years later, when cats having con-
evidenced by the decrease in heart rate, but not in sys-
reach the age at which hyperthyroidism most commonly
administered to hyperthyroid patients (Klein 2008).
occurs. Several studies have identified an association
The vascular effects of thyroid hormone mainly lead
between diet and hyperthyroidism, with hyperthyroid-
to vasodilation, and thus emerges a paradox: despite the
direct vasodilatory effect of thyroid hormone (mediated
by direct action of T3 on vascular smooth muscle cells) ism being 2–3 times more likely to occur in cats eating
canned food (Kass et al. 1999), threefold more likely in
(Ojamaa et al. 1996), the most common blood pressure cats specifically eating canned food from pop-top cans
abnormality in hyperthyroid patients is systemic hyper- (Edinboro et al. 2004), fourfold more likely in cats in
tension. The explanation lies in the greater degrees of which baby food was part of the diet (Edinboro et al.
increased systolic function and blood volume increase, 2004), and a 1.9-fold to 2.4-fold increased risk in cats
which surpass the effect of arterial dilation. Hyperthyroid that specifically ate fish or liver and giblets flavors of
patients, through vasodilation, also have activation of food as opposed to 11 other flavor types (Martin et al.
the renin-angiotensin-aldosterone system, and thus a 2000). It is theorized that goitrogenic substances (sub-
larger circulating plasma volume that limits the blood stances which elicit greater synthesis and release of
pressure effects of vasodilation; increased erythropoie- thyroid hormones) may be concentrated in certain
tin synthesis in hyperthyroidism results in a larger ingredients within canned foods, such as fish, liver, and
overall blood volume. giblets, or that the cans themselves may be of a composi-