Comparative cardiovascular toxicity in dogs given inotropic agents by continuous intravenous infusion

George Sandusky, J. R. Means, G. C. Todd

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A comparative study of the toxicity of the inotropic amines isoproterenol hydrochloride (IP), 1-norepinephrine bitatrate (NE), dopamine hydrochloride (DP), and dobutamine hydrochloride (DB) was conducted in beagle dogs (2/sex/dose group). All drugs were administered at doses that produced maximal contractile tension in dog myocardium. Doses, continuously infused for 96 hr, were 0.625, 1.25, and 2.5 μg/kg/min IP, 2.5 and 5 μg/kg/min NE, and 25, 50, and 100 μg/kg/min DP and DB. Three of 4 dogs that received 5 μg/kg/min NE and one of 4 given 100 μg/kg/min DP died. Pronounced tachycardia (mean peak rate increases from baseline of 88-104 beats/min) was observed at all doses of IP. DB produced a transient moderate tachycardia (mean peak rate increases from baseline of 25-27 beats/min) at 25 and 50 μg/kgμin and pronounced tachycardia (mean peak rate increases from baseline of 74 beats/min) at 100 μg/kg/min. Moderate bradycardia occurred at both doses of NE and at 25 and 50 μg/kg/min DP (mean peak rate decreases from baseline of 42-46 and 22-38 beats/min, respectively). At high doses the 4 inotropes produced focal to multifocal myocardial necrosis located mainly in left ventricle and segmental medial necrosis of the coronary arteries, mainly in small intramural muscular branches. Segmental medial hemorrhage was also seen following administration of high doses of NE and DP. An additional intramural coronary arterial lesion produced by all of the inotropes consisted of a mild periadventitial cellular infiltrate and fibroplasia. The results indicated that NE and DP produced the most severe cardiovascular lesions, followed by IP which produced lesions of more moderate severity. DB produced only slight lesions in comparison to the other 3 inotropic amines.

Original languageEnglish (US)
Pages (from-to)268-278
Number of pages11
JournalToxicologic Pathology
Volume18
Issue number2
StatePublished - 1990
Externally publishedYes

Fingerprint

Intravenous Infusions
Toxicity
Dopamine
Dobutamine
Dogs
Isoproterenol
Tachycardia
Amines
Necrosis
Bradycardia
Heart Ventricles
Coronary Vessels
Myocardium
Norepinephrine
Hemorrhage
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Comparative cardiovascular toxicity in dogs given inotropic agents by continuous intravenous infusion. / Sandusky, George; Means, J. R.; Todd, G. C.

In: Toxicologic Pathology, Vol. 18, No. 2, 1990, p. 268-278.

Research output: Contribution to journalArticle

@article{cbeb53e79cec4432b0a1621f5d194bd9,
title = "Comparative cardiovascular toxicity in dogs given inotropic agents by continuous intravenous infusion",
abstract = "A comparative study of the toxicity of the inotropic amines isoproterenol hydrochloride (IP), 1-norepinephrine bitatrate (NE), dopamine hydrochloride (DP), and dobutamine hydrochloride (DB) was conducted in beagle dogs (2/sex/dose group). All drugs were administered at doses that produced maximal contractile tension in dog myocardium. Doses, continuously infused for 96 hr, were 0.625, 1.25, and 2.5 μg/kg/min IP, 2.5 and 5 μg/kg/min NE, and 25, 50, and 100 μg/kg/min DP and DB. Three of 4 dogs that received 5 μg/kg/min NE and one of 4 given 100 μg/kg/min DP died. Pronounced tachycardia (mean peak rate increases from baseline of 88-104 beats/min) was observed at all doses of IP. DB produced a transient moderate tachycardia (mean peak rate increases from baseline of 25-27 beats/min) at 25 and 50 μg/kgμin and pronounced tachycardia (mean peak rate increases from baseline of 74 beats/min) at 100 μg/kg/min. Moderate bradycardia occurred at both doses of NE and at 25 and 50 μg/kg/min DP (mean peak rate decreases from baseline of 42-46 and 22-38 beats/min, respectively). At high doses the 4 inotropes produced focal to multifocal myocardial necrosis located mainly in left ventricle and segmental medial necrosis of the coronary arteries, mainly in small intramural muscular branches. Segmental medial hemorrhage was also seen following administration of high doses of NE and DP. An additional intramural coronary arterial lesion produced by all of the inotropes consisted of a mild periadventitial cellular infiltrate and fibroplasia. The results indicated that NE and DP produced the most severe cardiovascular lesions, followed by IP which produced lesions of more moderate severity. DB produced only slight lesions in comparison to the other 3 inotropic amines.",
author = "George Sandusky and Means, {J. R.} and Todd, {G. C.}",
year = "1990",
language = "English (US)",
volume = "18",
pages = "268--278",
journal = "Toxicologic Pathology",
issn = "0192-6233",
publisher = "SAGE Publications Inc.",
number = "2",

}

TY - JOUR

T1 - Comparative cardiovascular toxicity in dogs given inotropic agents by continuous intravenous infusion

AU - Sandusky, George

AU - Means, J. R.

AU - Todd, G. C.

PY - 1990

Y1 - 1990

N2 - A comparative study of the toxicity of the inotropic amines isoproterenol hydrochloride (IP), 1-norepinephrine bitatrate (NE), dopamine hydrochloride (DP), and dobutamine hydrochloride (DB) was conducted in beagle dogs (2/sex/dose group). All drugs were administered at doses that produced maximal contractile tension in dog myocardium. Doses, continuously infused for 96 hr, were 0.625, 1.25, and 2.5 μg/kg/min IP, 2.5 and 5 μg/kg/min NE, and 25, 50, and 100 μg/kg/min DP and DB. Three of 4 dogs that received 5 μg/kg/min NE and one of 4 given 100 μg/kg/min DP died. Pronounced tachycardia (mean peak rate increases from baseline of 88-104 beats/min) was observed at all doses of IP. DB produced a transient moderate tachycardia (mean peak rate increases from baseline of 25-27 beats/min) at 25 and 50 μg/kgμin and pronounced tachycardia (mean peak rate increases from baseline of 74 beats/min) at 100 μg/kg/min. Moderate bradycardia occurred at both doses of NE and at 25 and 50 μg/kg/min DP (mean peak rate decreases from baseline of 42-46 and 22-38 beats/min, respectively). At high doses the 4 inotropes produced focal to multifocal myocardial necrosis located mainly in left ventricle and segmental medial necrosis of the coronary arteries, mainly in small intramural muscular branches. Segmental medial hemorrhage was also seen following administration of high doses of NE and DP. An additional intramural coronary arterial lesion produced by all of the inotropes consisted of a mild periadventitial cellular infiltrate and fibroplasia. The results indicated that NE and DP produced the most severe cardiovascular lesions, followed by IP which produced lesions of more moderate severity. DB produced only slight lesions in comparison to the other 3 inotropic amines.

AB - A comparative study of the toxicity of the inotropic amines isoproterenol hydrochloride (IP), 1-norepinephrine bitatrate (NE), dopamine hydrochloride (DP), and dobutamine hydrochloride (DB) was conducted in beagle dogs (2/sex/dose group). All drugs were administered at doses that produced maximal contractile tension in dog myocardium. Doses, continuously infused for 96 hr, were 0.625, 1.25, and 2.5 μg/kg/min IP, 2.5 and 5 μg/kg/min NE, and 25, 50, and 100 μg/kg/min DP and DB. Three of 4 dogs that received 5 μg/kg/min NE and one of 4 given 100 μg/kg/min DP died. Pronounced tachycardia (mean peak rate increases from baseline of 88-104 beats/min) was observed at all doses of IP. DB produced a transient moderate tachycardia (mean peak rate increases from baseline of 25-27 beats/min) at 25 and 50 μg/kgμin and pronounced tachycardia (mean peak rate increases from baseline of 74 beats/min) at 100 μg/kg/min. Moderate bradycardia occurred at both doses of NE and at 25 and 50 μg/kg/min DP (mean peak rate decreases from baseline of 42-46 and 22-38 beats/min, respectively). At high doses the 4 inotropes produced focal to multifocal myocardial necrosis located mainly in left ventricle and segmental medial necrosis of the coronary arteries, mainly in small intramural muscular branches. Segmental medial hemorrhage was also seen following administration of high doses of NE and DP. An additional intramural coronary arterial lesion produced by all of the inotropes consisted of a mild periadventitial cellular infiltrate and fibroplasia. The results indicated that NE and DP produced the most severe cardiovascular lesions, followed by IP which produced lesions of more moderate severity. DB produced only slight lesions in comparison to the other 3 inotropic amines.

UR - http://www.scopus.com/inward/record.url?scp=0025161215&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025161215&partnerID=8YFLogxK

M3 - Article

VL - 18

SP - 268

EP - 278

JO - Toxicologic Pathology

JF - Toxicologic Pathology

SN - 0192-6233

IS - 2

ER -