Characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys

Minomo, Hirofumi; Torikai, Yusuke; Furukawa, Tomohiro; Uchino, Hiroshi; Kadokura, Hidetomi; Nakama, Kazuhiro; Maeda, Hiroshi; Kamenosono, Takeshi; Sukamoto, Takayuki; Fukuzaki, Koichiro; Nagata, Ryoichi

doi:10.2131/jts.34.589

Cited by 9 publications

(6 citation statements)

References 12 publications

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“…However, with a larger insult and/or ongoing cardiomyocyte necrosis, increases in cTnI can be much greater in magnitude than those seen associated with chair restraint and can be sustained past 24 HPD. This was recently demonstrated in a study where monkeys were administered isoproterenol, and vasopressin and cTnI concentrations peaked at 4 to 6 hr after a single dose and remained increased 3 to 4 days after dosing (Minomo et al 2009). At the highest dose of isoproterenol used, peak mean cTnI values were ∼10 ng/ml, utilizing an ELISA.…”

Section: Discussionmentioning

confidence: 71%

“…remained increased 3 to 4 days after dosing (Minomo et al 2009). At the highest dose of isoproterenol used, peak mean cTnI values were *10 ng/ml, utilizing an ELISA.…”

Section: Discussionmentioning

confidence: 97%

“…In 2012, cTnI was qualified by the FDA as a marker of cardiac necrosis in rats and dogs for use in preclinical studies (Woodcock 2012). At the time the qualification document was submitted in late 2008, there were limited published studies demonstrating the use of this biomarker in nonhuman primates (NHP) studies, although more recently, additional publications have become available (Dunn et al 2012; Minomo et al 2009; Schultze et al 2015; Takeuchi et al 2008; Zabka, Irwin, and Albassam 2009). Based on the paucity of published information on the use of this biomarker in NHP at the time of submission, cTnI was not officially qualified for use in NHP.…”

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confidence: 99%

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Assessment of Cardiac Troponin I Responses in Nonhuman Primates during Restraint, Blood Collection, and Dosing in Preclinical Safety Studies

et al. 2016

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Limited information has been published on the use of cardiac troponin I (cTnI) as a biomarker of cardiac injury in monkeys. The purpose of these studies was to characterize the cTnI response seen in cynomolgus macaques during routine dosing and blood collection procedures typically used in preclinical safety studies and to better understand the pathogenesis of this response. We measured cTnI using two different methods, the Siemens Immulite cTnI assay and the more sensitive Siemens Troponin I-Ultra assay. We were able to demonstrate that after oral, subcutaneous, or intravenous dosing of common vehicles, as well as serial chair restraint for venipuncture blood collection, that minimal to mild transient increases in cTnI could be detected in monkeys with both assays. cTnI values typically peaked at 2, 3, 4, or 6 hr after sham dosing and returned to baseline at 22 or 24 hr. In addition, marked increases in heart rate (HR) and blood pressure (BP) occurred in monkeys during the restraint procedures, which likely initiated the cTnI release in these animals. Monkeys that were very well acclimated to the chairing procedures and had vascular access ports for blood sampling did not have marked increases in HRs and BP or increases in cTnI.

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Section: Discussionmentioning

confidence: 71%

“…remained increased 3 to 4 days after dosing (Minomo et al 2009). At the highest dose of isoproterenol used, peak mean cTnI values were *10 ng/ml, utilizing an ELISA.…”

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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Assessment of Cardiac Troponin I Responses in Nonhuman Primates during Restraint, Blood Collection, and Dosing in Preclinical Safety Studies

et al. 2016

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“…The cTnI has been studied very little in wild animal medicine. Some studies have evaluated the value of cTnI as a cardiac biomarker in non‐human primates; however, this is the first report of cTnI as a cardiac biomarker in Alouatta sp .…”

Section: Discussionmentioning

confidence: 99%

Bacterial endocarditis and increased cardiac troponin I levels in a brown howler monkey (Alouatta guariba clamitans) with an interventricular septal defect

Zafalon-Silva

Soares²,

Pavarini

et al. 2018

J of Medical Primatology

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“…Serum cTnI is a sensitive marker of myocardial injury in all species, including the cynomolgus monkey (Apple et al 2008; Minomo et al 2009). At the onset of myocardial necrosis in the monkey, cTnI is rapidly released into the blood in an amount and duration that depends on the size of the affected tissue (Minomo et al 2009). Persistent high concentrations of serum cTnI are the result of continued leaching of cTnI from the remains of necrotic cells (Hickman et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Myocardial Mononuclear Cell Infiltrates Are Not Associated with Increased Serum Cardiac Troponin I in Cynomolgus Monkeys

et al. 2012

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Myocardial mononuclear cell infiltrate is a spontaneous cardiac finding commonly identified in laboratory cynomolgus monkeys. The infiltrates are predominantly composed of macrophages with lesser lymphocytes and are not typically associated with histologically detectable cardiomyocyte degeneration. These infiltrates are of concern because they confound interpretation of test article-related histopathology findings in nonclinical safety toxicology studies. The interpretation of safety studies would be simplified by a biomarker that could identify myocardial infiltrates prior to animal placement on study. We hypothesized that monkeys with myocardial mononuclear cell infiltrates could be identified before necropsy using an ultrasensitive immunoassay for cardiac troponin I (cTnI). Serum cTnI concentrations in monkeys with myocardial infiltrates were not higher than those in monkeys without infiltrates at any of the sampling times before and on the day of necropsy. Increased serum cTnI levels are not suitable for screening monkeys with myocardial mononuclear cell infiltrates before placement in the study.

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Characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys

Cited by 9 publications

References 12 publications

Assessment of Cardiac Troponin I Responses in Nonhuman Primates during Restraint, Blood Collection, and Dosing in Preclinical Safety Studies

Assessment of Cardiac Troponin I Responses in Nonhuman Primates during Restraint, Blood Collection, and Dosing in Preclinical Safety Studies

Bacterial endocarditis and increased cardiac troponin I levels in a brown howler monkey (Alouatta guariba clamitans) with an interventricular septal defect

Myocardial Mononuclear Cell Infiltrates Are Not Associated with Increased Serum Cardiac Troponin I in Cynomolgus Monkeys

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