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Limited Additional Release of Cardiac Troponin I and T in Isoproterenol-Treated Beagle Dogs with Cardiac Injury

Johnson & Johnson Pharmaceutical, Research & Development L.L.C., Global Preclinical Development, Raritan, NJ

^aAddress correspondence to this author at: Johnson & Johnson Pharmaceutical Research & Development L.L.C., Global Preclinical Development, PO Box 300, 1001 Route 202 North, Raritan, NJ 08869.

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To the Editor:

Many studies have shown that determination of the blood concentrations of cardiac troponin I and T (cTnI and cTnT) offers higher clinical sensitivity and specificity for the diagnosis of cardiac injury than do the standard cardiac protein markers such as creatine kinase (CK) (1)(2). However, the release of cardiac troponins into the blood stream of laboratory animals in response to cardiac insults such as drugs is still not well defined. It was our objective to examine the release of cardiac troponins together with CK by repeat dosing in isoproterenol (ISO)-treated beagle dogs, a routinely used animal model in preclinical studies.

ISO is a sympathomimetic agent and ß-adrenergic receptor agonist that causes acute cardiac injury at high doses (3). In the present study, 1 male and 1 female beagle dog (9 months old) were given a 1 mg/kg subcutaneous injection of ISO on each of 2 consecutive days. Abnormal pathologic alterations, including severe coagulative necrosis, were observed in both animals. Blood was collected from the jugular vein into collection tubes (Beckon Dickinson) containing EDTA for the analysis of cardiac troponins and into the same type tubes with no additive for CK. The blood concentration of cTnI was measured by a modified Access® AccuTnI^TM immunoassay (Beckman-Coulter) performed manually on 96-well plates according to the manufacturer’s recommended experimental conditions. cTnT was determined by an ELISA containing a biotinylated monoclonal . . . [Full Text of this Article]