Page 74 - Feline Cardiology

70 Section B: Diagnostic Testing

B 12 concentrations than the healthy controls. However, this study validated a human ET-1 ELISA assay in the
it was unclear whether these changes were secondary or cat, it also demonstrated that ET-1 was unable to dis-
primary and further studies are warranted. A separate criminate asymptomatic cats from symptomatic cats
group of researchers found that plasma homocysteine with heart failure or arterial thromboembolism (Prosek
was significantly elevated in cats with CHF and ATE 2004a).
Diagnostic Testing homocysteine levels were elevated in the CHF (without that have been best studied in the cat and that are readily
At this time in veterinary cardiology, the biomarkers
compared to normal cats. However, although plasma
available for clinical use are the cardiac troponins and
ATE) group compared to normal cats, it was not signifi-
the natriuretic peptides. The remainder of this chapter
cantly different, nor was there a significant difference in
focuses on these biomarkers.
plasma homocysteine levels between the CHF groups
with and without ATE (Hohenhaus et al. 1999).
CARDIAC TROPONINS
ENDOTHELIN I
Cardiac troponin I and T are specific markers of myocyte
Endothelin (ET-1) is a powerful stimulant of vascular injury. Troponins (Tn) are regulatory proteins that are
smooth muscle contraction and proliferation as well as part of the contractile apparatus of skeletal and cardiac
myocardial fibrosis. It also potentiates other neurohor- muscle tissue. They are not present in smooth muscle
mones (Braunwald 2008). ET-1 is produced within tissue. With the proteins actin and tropomyosin, they
endothelial cells in response to various stimuli, includ- make up the thin filaments within the myofibrils that are
ing shear stress, hypoxia, and the presence of other cir- essential for the calcium-mediated regulation of muscle
culating vasoactive hormones such as angiotensin II and contraction. The troponin complex consists of three
vasopressin. Along with the RAAS system, ET-1 contrib- interacting and functionally distinct proteins (troponin
utes to pathologic cardiac remodeling by inducing car- I, T, and C). Each troponin protein has specific functions
diomyocyte hypertrophy and activation of cardiac that regulate muscle contraction (see Figure 11.1).
fibroblasts. After elevated plasma B-type natriuretic Troponin C binds calcium to initiate muscle contrac-
peptide levels, an increase in plasma levels of big endo- tion and is present in two isoforms. Homology between
thelin (the prohormone that is converted to ET-1) was the cardiac isoform and one of the skeletal muscle iso-
the most powerful predictor of mortality and hospital- forms reduces the cardiac specificity of TnC and there-
ization for heart failure in a human study (Braunwald fore limits its diagnostic usefulness in heart disease
2008). Moreover, ET-1 levels correlated with the severity (Schreier et al. 1990). Troponin T attaches the troponin
of heart failure class and degree of hemodynamic complex to tropomyosin and actin (Filatov 1999). In
impairment (Wei 1994), and elevated ET-1 was associ- human cardiac tissue four isoforms exist, but only one
ated with higher 1-year mortality in people with heart is characteristic of the adult heart. The other three
failure, suggesting that routine monitoring may provide cardiac isoforms are expressed in fetal tissue. The fetal
important prognostic information in people with mild isoforms may be reexpressed during heart failure or in
to moderate heart failure (Pousset et al. 1997). However, damaged skeletal muscle. Troponin I inhibits actomyo-
several ET-1 receptor antagonists have failed to show sin ATPase and prevents the structural interaction of
clinical benefit in more recent human trials (Rich and myosin with the actin–binding sites. The binding of
McLaughlin 2003). calcium to troponin C displaces troponin I and causes a
Several veterinary studies have identified that ET-1 conformational change in tropomyosin so that it no
may be a prognostic indicator of early mortality in dogs longer interferes with myosin/actin binding and muscle
with heart failure or severe pulmonary disease (O’Sullivan contraction can occur. Three isoforms exist for troponin
et al. 2007; Tessier-Vetzel et al. 2006). ET-1 was increased I. Two are present in skeletal muscle and the other is
in dogs with heart failure compared to normal dogs or present only in cardiac muscle. Unlike cardiac TnT,
dogs with asymptomatic heart disease, but it was not cardiac TnI is not expressed in fetal skeletal muscle
different between asymptomatic dogs and normal dogs during development, nor after damage and regeneration
(Prosek 2004b). One feline study evaluated ET-1 in in adult skeletal muscle (Bodor et al. 1995).
healthy control cats (n = 12), asymptomatic cats with Troponins are considered leakage markers. Damage to
various cardiomyopathies (n = 12) and symptomatic cardiac myocytes resulting in loss of membrane integrity
cats with heart failure (n = 15) or arterial thromboem- allows the release of cardiac Tn into the circulation.
bolism (n = 4) (Prosek 2004a). ET-1 was increased in Troponin release kinetics are consistent with two sepa-
asymptomatic cats compared to normal cats and in rate intracellular populations. After acute cardiac injury,
symptomatic cats compared to normal cats. Although the cytosolic pool is released resulting in an early rise in