Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs

Anastasia S. Mihailidou, Rosemarie Einstein, Desmond P. Richardson, Peter Gray, Michael P. Jones, Stephen N. Hunyor

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Study objective - The aim of the study was to evaluate the effect of chronic digoxin therapy on cardiac sensitivity to isoprenaline.Design - Responses to isoprenaline were examined in both conscious and anaesthetised dogs pretreated with digoxin, and compared with conscious or anaesthetised controls with no digoxin pretreatment. Isoprenaline infusion (0.001-0.1 μg·kg-1·min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero.Subjects - Mongrel dogs of either sex (15-25 kg) were used in the experiments, done under anaesthetic. They were divided into three groups (n=6 per group): group A were controls; groups B and C were pretreated with digoxin 500-750 μg.d-1, for 14 d (B) and 7 d (C). For the experiments in conscious animals, six mongrel dogs (25-30 kg) and two greyhounds (25-30 kg) were used; group D (n=6) were treated with digoxin for 20-40 d; group E (n=2) were treated for 7 d.Measurements and results - Heart rate, blood pressure and myocardial contractility (dP/dt: integrated isometric tension) were measured during isoprenaline infusion. Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal. When the pretreatment period was reduced to 7 d there was no change in any of the responses to isoprenaline. In conscious dogs there was also a significant increase in inotropic sensitivity to isoprenaline after digoxin withdrawal, but this was not so marked as in anaesthetised dogs. In conscious dogs chronotropic sensitivity to isoprenaline was also increased.Conclusions - It is possible that the inotropic effect maintained during the 2 weeks of digoxin treatment may cause substantial withdrawal of sympathetic tone to the heart, with a consequent increase in β adrenoceptor number or sensitivity, which could be detected a week after digoxin withdrawal.

LanguageEnglish
Pages222-226
Number of pages5
JournalCardiovascular Research
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 1990
Externally publishedYes

Fingerprint

Digoxin
Isoproterenol
Dogs
Adrenergic Receptors
Anesthetics
Heart Rate
Blood Pressure

Keywords

  • β adrenoceptor
  • Anaesthetised
  • Chronotropic
  • Conscious
  • Digoxin
  • Dog
  • Inotropic
  • Isoprenaline

Cite this

Mihailidou, Anastasia S. ; Einstein, Rosemarie ; Richardson, Desmond P. ; Gray, Peter ; Jones, Michael P. ; Hunyor, Stephen N. / Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs. In: Cardiovascular Research. 1990 ; Vol. 24, No. 3. pp. 222-226.
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abstract = "Study objective - The aim of the study was to evaluate the effect of chronic digoxin therapy on cardiac sensitivity to isoprenaline.Design - Responses to isoprenaline were examined in both conscious and anaesthetised dogs pretreated with digoxin, and compared with conscious or anaesthetised controls with no digoxin pretreatment. Isoprenaline infusion (0.001-0.1 μg·kg-1·min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero.Subjects - Mongrel dogs of either sex (15-25 kg) were used in the experiments, done under anaesthetic. They were divided into three groups (n=6 per group): group A were controls; groups B and C were pretreated with digoxin 500-750 μg.d-1, for 14 d (B) and 7 d (C). For the experiments in conscious animals, six mongrel dogs (25-30 kg) and two greyhounds (25-30 kg) were used; group D (n=6) were treated with digoxin for 20-40 d; group E (n=2) were treated for 7 d.Measurements and results - Heart rate, blood pressure and myocardial contractility (dP/dt: integrated isometric tension) were measured during isoprenaline infusion. Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal. When the pretreatment period was reduced to 7 d there was no change in any of the responses to isoprenaline. In conscious dogs there was also a significant increase in inotropic sensitivity to isoprenaline after digoxin withdrawal, but this was not so marked as in anaesthetised dogs. In conscious dogs chronotropic sensitivity to isoprenaline was also increased.Conclusions - It is possible that the inotropic effect maintained during the 2 weeks of digoxin treatment may cause substantial withdrawal of sympathetic tone to the heart, with a consequent increase in β adrenoceptor number or sensitivity, which could be detected a week after digoxin withdrawal.",
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Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs. / Mihailidou, Anastasia S.; Einstein, Rosemarie; Richardson, Desmond P.; Gray, Peter; Jones, Michael P.; Hunyor, Stephen N.

In: Cardiovascular Research, Vol. 24, No. 3, 03.1990, p. 222-226.

Research output: Contribution to journalReview articleResearchpeer-review

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T1 - Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs

AU - Mihailidou, Anastasia S.

AU - Einstein, Rosemarie

AU - Richardson, Desmond P.

AU - Gray, Peter

AU - Jones, Michael P.

AU - Hunyor, Stephen N.

PY - 1990/3

Y1 - 1990/3

N2 - Study objective - The aim of the study was to evaluate the effect of chronic digoxin therapy on cardiac sensitivity to isoprenaline.Design - Responses to isoprenaline were examined in both conscious and anaesthetised dogs pretreated with digoxin, and compared with conscious or anaesthetised controls with no digoxin pretreatment. Isoprenaline infusion (0.001-0.1 μg·kg-1·min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero.Subjects - Mongrel dogs of either sex (15-25 kg) were used in the experiments, done under anaesthetic. They were divided into three groups (n=6 per group): group A were controls; groups B and C were pretreated with digoxin 500-750 μg.d-1, for 14 d (B) and 7 d (C). For the experiments in conscious animals, six mongrel dogs (25-30 kg) and two greyhounds (25-30 kg) were used; group D (n=6) were treated with digoxin for 20-40 d; group E (n=2) were treated for 7 d.Measurements and results - Heart rate, blood pressure and myocardial contractility (dP/dt: integrated isometric tension) were measured during isoprenaline infusion. Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal. When the pretreatment period was reduced to 7 d there was no change in any of the responses to isoprenaline. In conscious dogs there was also a significant increase in inotropic sensitivity to isoprenaline after digoxin withdrawal, but this was not so marked as in anaesthetised dogs. In conscious dogs chronotropic sensitivity to isoprenaline was also increased.Conclusions - It is possible that the inotropic effect maintained during the 2 weeks of digoxin treatment may cause substantial withdrawal of sympathetic tone to the heart, with a consequent increase in β adrenoceptor number or sensitivity, which could be detected a week after digoxin withdrawal.

AB - Study objective - The aim of the study was to evaluate the effect of chronic digoxin therapy on cardiac sensitivity to isoprenaline.Design - Responses to isoprenaline were examined in both conscious and anaesthetised dogs pretreated with digoxin, and compared with conscious or anaesthetised controls with no digoxin pretreatment. Isoprenaline infusion (0.001-0.1 μg·kg-1·min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero.Subjects - Mongrel dogs of either sex (15-25 kg) were used in the experiments, done under anaesthetic. They were divided into three groups (n=6 per group): group A were controls; groups B and C were pretreated with digoxin 500-750 μg.d-1, for 14 d (B) and 7 d (C). For the experiments in conscious animals, six mongrel dogs (25-30 kg) and two greyhounds (25-30 kg) were used; group D (n=6) were treated with digoxin for 20-40 d; group E (n=2) were treated for 7 d.Measurements and results - Heart rate, blood pressure and myocardial contractility (dP/dt: integrated isometric tension) were measured during isoprenaline infusion. Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal. When the pretreatment period was reduced to 7 d there was no change in any of the responses to isoprenaline. In conscious dogs there was also a significant increase in inotropic sensitivity to isoprenaline after digoxin withdrawal, but this was not so marked as in anaesthetised dogs. In conscious dogs chronotropic sensitivity to isoprenaline was also increased.Conclusions - It is possible that the inotropic effect maintained during the 2 weeks of digoxin treatment may cause substantial withdrawal of sympathetic tone to the heart, with a consequent increase in β adrenoceptor number or sensitivity, which could be detected a week after digoxin withdrawal.

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KW - Anaesthetised

KW - Chronotropic

KW - Conscious

KW - Digoxin

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KW - Isoprenaline

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