A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys

James D. Wilkinson, Ralph Callicott, William F. Salminen, Satinder K Sandhu, James Greenhaw, Angel Paredes, Kelly Davis, Yvonne Jones, Merle G. Paule, William Slikker, Paolo Rusconi, Jason Czachor, Amy Bodien, Joslyn A. Westphal, Danielle D. Dauphin, Steven E. Lipshultz

Research output: Contribution to journalArticle

Abstract

Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing. Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose–response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P =.0006). Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.

Original languageEnglish (US)
JournalPediatric Research
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Methylphenidate
Macaca mulatta
Clinical Pathology
Myoglobin
Electrocardiography
Biomarkers
Serum
Biopsy
Animal Models
Control Groups

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys. / Wilkinson, James D.; Callicott, Ralph; Salminen, William F.; Sandhu, Satinder K; Greenhaw, James; Paredes, Angel; Davis, Kelly; Jones, Yvonne; Paule, Merle G.; Slikker, William; Rusconi, Paolo; Czachor, Jason; Bodien, Amy; Westphal, Joslyn A.; Dauphin, Danielle D.; Lipshultz, Steven E.

In: Pediatric Research, 01.01.2018.

Research output: Contribution to journalArticle

Wilkinson, JD, Callicott, R, Salminen, WF, Sandhu, SK, Greenhaw, J, Paredes, A, Davis, K, Jones, Y, Paule, MG, Slikker, W, Rusconi, P, Czachor, J, Bodien, A, Westphal, JA, Dauphin, DD & Lipshultz, SE 2018, 'A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys', Pediatric Research. https://doi.org/10.1038/s41390-018-0256-9
Wilkinson, James D. ; Callicott, Ralph ; Salminen, William F. ; Sandhu, Satinder K ; Greenhaw, James ; Paredes, Angel ; Davis, Kelly ; Jones, Yvonne ; Paule, Merle G. ; Slikker, William ; Rusconi, Paolo ; Czachor, Jason ; Bodien, Amy ; Westphal, Joslyn A. ; Dauphin, Danielle D. ; Lipshultz, Steven E. / A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys. In: Pediatric Research. 2018.
@article{441f98013b904cf1803f126872d6e956,
title = "A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys",
abstract = "Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing. Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose–response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P =.0006). Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.",
author = "Wilkinson, {James D.} and Ralph Callicott and Salminen, {William F.} and Sandhu, {Satinder K} and James Greenhaw and Angel Paredes and Kelly Davis and Yvonne Jones and Paule, {Merle G.} and William Slikker and Paolo Rusconi and Jason Czachor and Amy Bodien and Westphal, {Joslyn A.} and Dauphin, {Danielle D.} and Lipshultz, {Steven E.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1038/s41390-018-0256-9",
language = "English (US)",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys

AU - Wilkinson, James D.

AU - Callicott, Ralph

AU - Salminen, William F.

AU - Sandhu, Satinder K

AU - Greenhaw, James

AU - Paredes, Angel

AU - Davis, Kelly

AU - Jones, Yvonne

AU - Paule, Merle G.

AU - Slikker, William

AU - Rusconi, Paolo

AU - Czachor, Jason

AU - Bodien, Amy

AU - Westphal, Joslyn A.

AU - Dauphin, Danielle D.

AU - Lipshultz, Steven E.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing. Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose–response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P =.0006). Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.

AB - Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing. Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose–response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P =.0006). Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.

UR - http://www.scopus.com/inward/record.url?scp=85060190533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060190533&partnerID=8YFLogxK

U2 - 10.1038/s41390-018-0256-9

DO - 10.1038/s41390-018-0256-9

M3 - Article

C2 - 30555154

AN - SCOPUS:85060190533

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

ER -