Short-term increase of serum troponin I and serum heart-type fatty acid-binding protein (H-FABP) in dogs following administration of formoterol

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2010-07, Vol.62 (4), p.343-352
• Main Authors: Strauss, Volker, Wöhrmann, Thomas, Frank, Ilona, Hübel, Ulrich, Luft, Jörg, Bode, Gerd, Germann, Paul-Georg
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; Animals; Biological and medical sciences; Biomarkers - blood; Circadian Rhythm; CK isoenzymes; Delayed-Action Preparations; Dog; Dogs; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines - administration & dosage; Ethanolamines - adverse effects; Fatty Acid-Binding Proteins - blood; Female; Formoterol; Formoterol Fumarate; Glucocorticoid; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Heart-type fatty acid-binding protein; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Myocardial Ischemia - blood; Myocardial Ischemia - chemically induced; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Time Factors; Troponin I; Troponin I - blood
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2009.05.006

In this paper, changes in serum levels of the cardiac biomarkers troponin I and the heart-type fatty acid-binding protein (H-FABP) following administration of a long-acting β 2-sympathicomimeticum (long-acting beta-agonist, LABA) to dogs were measured. We measured troponin I in dogs in a 4-week repeated-dose study with inhalative administration of formoterol (13 μg/kg d) and a glucocorticoid/formoterol combination (143/16 μg/kg d). The medians of troponin I increased within 3 days in both groups, far beyond the cut-off level (0.1 μg/L), but returned to baseline levels on study day 9. The increase was more pronounced in the formoterol-only group (3.29 μg/L) compared to the glucocorticoid/formoterol combination group (1.32 μg/L). In a second study, we measured serum troponin I as well as serum H-FABP levels in several samples over 7 days in dogs, receiving a single inhalative dose of a glucocorticoid/formoterol combination (120/12 μg/kg d). The median of the troponin I concentration increased above the cut-off level within 2 h and that of H-FABP within 4 h. The medians of both parameters were temporarily above the cut-off levels even on study day 7. Both studies were conducted according to national animal welfare guidelines. To our knowledge, this is the first report that shows a corresponding increase of troponin I and H-FABP in dogs treated with formoterol. Both parameters are more sensitive in detecting a drug-induced cardiac injury compared to total LDH, total CK as well as CK MB activity. However, it is recommended to take at least three blood samples per day to assess a temporary increase of troponin I.