Tolerance to dobutamine after a 72 hour continuous infusion

Unverferth, Donald V.; Blanford, Marvin F.; Kates, Robert E.; Leier, Carl V.

doi:10.1016/0002-9343(80)90387-3

Cited by 232 publications

(44 citation statements)

References 16 publications

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“…This exercise-mimicking phenomenon is the basis upon which dobutamine may be used as a pharmacological stress agent for diagnostic perfusion imaging, 10 but conversely, it may limit its utility in clinical conditions in which induction of ischemia is potentially harmful. Tolerance can develop after just a few days of therapy, 11 and malignant ventricular arrhythmias can be observed at any dose.…”

mentioning

confidence: 99%

Inotropes and Vasopressors

2008

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mentioning

confidence: 99%

Inotropes and Vasopressors

2008

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“…It is not known whether a selective stimulatory effect on the B1AR subtype or partial intrinsic activity is responsible for the weak desensitization in vivo. In contrast, tolerance to dobutamine easily develops in cardiac tissue in vivo (14). In several studies dealing with PAR desensitization, norepinephrine is used for chronic treatment (15 -18).…”

mentioning

confidence: 99%

Desensitization and Selective Down-Regulation of Rat Cardiac β1-Adrenoceptors by Prolonged In Vivo Infusion of T-0509, a β1-Adrenoceptor Full Agonist

Sato¹,

Adachi‐Akahane²,

Prados

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-We studied the effects of prolonged infusion of a selective ~1-adrenoceptor (f3,AR) fullhydrochloride], with regard to its inotropic effect in vivo and cardiac (3AR density. The results were compared with those for isoproterenol. Continuous infusion of isoproterenol at doses of 2.5-40 ,ug/kg/hr, s.c. for 6 days shifted the dose-response curves of isoproterenol (i.v.) for LVdP/dtmx to the right and increased the ED50 values up to fourfold. Isoproterenol infusion at 40 pg/kg/hr reduced the density of both r3,-and ~2ARs by 36010 and 43070 respectively, in left ventricular membranes. Following 6-day infusion of T-0509 at doses sufficient to induce a positive inotropic effect (5-40 rig/kg/hr), the ED50 value of T-0509 (i.v.) for LVdP/dtmax was also increased up to fourfold. In contrast to isoproterenol, infusion of T-0509 caused selective down-regulation of (3,ARs by 30% without changing the number of hARs. These results indicate that long-term application of a selective /31AR full agonist causes desensitization to its inotropy in vivo, with subtype-selective down-regulation of ~1ARs in cardiac ventricles.

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“…22,23 As β 1 -AR downregulation is secondary to prolonged exposure to the agonist, tolerance development with decrease in the hemodynamic response to dobutamine has been described after days of continuous dobutamine infusion. 24 Dobutamine has a milder effect on β 2 -ARs, which cause vascular smooth muscle relaxation. This effect is partially counterbalanced by α-1 AR stimulation so that dobutamine net effects on the peripheral vessels are of mild vasodilation or neutral.…”

Section: Dobutaminementioning

confidence: 99%

Old and New Intravenous Inotropic Agents in the Treatment of Advanced Heart Failure

Metra

Bettari

Carubelli

et al. 2011

Progress in Cardiovascular Diseases

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Inotropic agents are administered to improve cardiac output and peripheral perfusion in patients with systolic dysfunction and low cardiac output. However, there is evidence of increased mortality and adverse effects associated with current inotropic agents. These adverse outcomes may be ascribed to patient selection, increased myocardial energy expenditure and oxygen consumption, or to specific mechanisms of action. Both sympathomimetic amines and type III phosphodiesterase inhibitors act through an increase in intracellular cyclic adenosine monophoshate and free calcium concentrations, mechanisms that increase oxygen consumption and favor arrhythmias. Concomitant peripheral vasodilation with some agents (phosphodiesterase inhibitors and levosimendan) may also lower coronary perfusion pressure and favor myocardial damage. New agents with different mechanisms of action might have a better benefit to risk ratio and allow an improvement in tissue and end-organ perfusion with less untoward effects. We have summarized the characteristics of the main inotropic agents for heart failure treatment, the data from randomized controlled trials, and future perspectives for this class of drugs. (Prog Cardiovasc Dis 2011;54:97-106)

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Tolerance to dobutamine after a 72 hour continuous infusion

Cited by 232 publications

References 16 publications

Inotropes and Vasopressors

Inotropes and Vasopressors

Desensitization and Selective Down-Regulation of Rat Cardiac β1-Adrenoceptors by Prolonged In Vivo Infusion of T-0509, a β1-Adrenoceptor Full Agonist

Old and New Intravenous Inotropic Agents in the Treatment of Advanced Heart Failure

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