Circulating Cardiac Troponins in Small Animals

INTRODUCTION The cardiac troponins I, T, and C (cTnI, cTnT, and cTnC) are thin filament-associated regulatory proteins of the heart muscle. They are crucial to the interaction between actin and myosin and occur at regular intervals of 38 nm along the tropomyosin molecule. Cardiac troponin I ("I" for inhibition) is uniquely expressed in the myocardium and is a potent inhibitor of the process of actin-myosin cross-bridge formation. The molecular weight is 24.000 D. Cardiac troponin I has been investigated extensively in people and has been found to be a very sensitive serum marker of physical or metabolic myocardial injury, myocardial ischemia, or necrosis with a cardiac specificity of 100%. Cardiac troponin T ("T" for tropomyosin binding) has a molecular weight of 37.000 D and binds the troponin complex to tropomyosin. The cardiac specificity of serum cTnT is less than 100% because it may be re-expressed in skeletal muscle during regeneration processes after trauma and may also be elevated in renal disease or acute pulmonary thromboembolism. Cardiac troponin C ("C" for calcium) binds to calcium and starts, therefore, the crossbridge cycle. However, it has not gained any diagnostic significance yet. As with cTnI, approximately 95% of cTnT in man and dogs is myofibril bound and about 5% is cytosolically dissolved. Mechanisms for an elevation in circulating cardiac troponins include an increase of myocyte membrane permeability (initial release of the cytosolic troponin pool) or cell necrosis (release of myofibrilbound troponins). Four to six hours after acute myocardial cell injury, the cardiac troponin concentration in blood increases in a biphasic pattern. A rather low initial elevation is followed by a more pronounced release of structurally bound cardiac troponins depending on severity of the lesion. Plasma half-life of cardiac troponins is approximately two hours, and elimination mainly occurs via the reticuloendothelial system (cTnI and cTnT) and renal loss (cTnT). Troponins from cardiac muscle and slow-and fast-twitch skeletal muscle are products of different genes with unique amino acid sequences. Thus, recently developed monoclonal antibodies to cTnI have no and to cTnT only minor cross-reactivity with skeletal muscle isoforms. Cardiac troponins are phylogenetically highly preserved proteins with a more than 95% total structural agreement between mammals. Therefore, established human serologic tests for troponin analysis may be used reliably in pets as well. In normal dogs and cats, serum cTnT is less than 0.1 ng/ml and serum cTnI is less than 0.5 ng/ml. The cut-off level of serum cardiac troponins to separate significant from non-significant myocardial cell injury in people is 0.1 ng/ml for cTnT and 2.0 ng/ml for cTnI. Myocardial cell injury, manifested anatomically as inflammation (endomyocarditis, myocarditis, perimyocarditis), acute degeneration, apoptosis, or necrosis or hemodynamically as transient or permanent cardiac contractile dysfunction, is a frequent consequence of physical myocardial trauma (cardiac contusion), cardiomyopathy, metabolic (diabetes mellitus, renal insufficiency, pancreatitis) or toxic myocardial damage (anthracyclines, catecholamines, bacterial endotoxins, tumor necrosis factor), myocardial ischemia (tachycardiainduced, pathologic hypertrophy with small vessel disease, arterosclerosis) or infarction. Diagnostic sensitivity of electrocardiography (ECG) or echocardiography to diagnose minor myocardial injury is poor. However, early diagnosis of myocardial injury may be important from a therapeutic and prognostic perspective.