Muscarinic receptor modulation of basal and beta-adrenergic stimulated function of the failing human left ventricle.

Newton, Gary E.; Parker, Andrea B.; Landzberg, Joel S.; Colucci, Wilson S.; Parker, John D.

doi:10.1172/jci119101

Cited by 50 publications

(23 citation statements)

References 36 publications

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“…The administration of dobutamine by the intravenous or intracoronary route is a well-established method of assessing ␤-adrenergic responsiveness in humans. 11,20,22 In this study, the vitamin C-mediated augmentation of the dobutamine response was similar in magnitude to that observed with parasympathetic blockade in humans with normal ventricular function 11 as well as nitric oxide synthase blockade in patients with CHF. 20 In the experimental group, it is unlikely that the inotropic response to the second dobutamine infusion was potentiated by the previous dobutamine infusion, because no significant difference in the dP/dt response was observed between successive dobutamine infusions in the control group.…”

Section: Discussionsupporting

confidence: 79%

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

Mak

Newton

2001

Circulation

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Background-We studied the effect of an antioxidant, the intracoronary infusion of vitamin C, on basal and dobutamine-stimulated left ventricular (LV) contractility. Methods and Results-Nineteen patients with normal ventricular function participated in this study. A micromanometertipped catheter was inserted into the LV. In the experimental group (nϭ10), an infusion catheter was positioned in the left main coronary artery. LV peak ϩdP/dt (LV ϩdP/dt) was measured in response to the intravenous infusion of dobutamine before (Dob) and during (Dobϩvit C) the intracoronary infusion of vitamin C. The intracoronary infusion of vitamin C had no effect on basal LV ϩdP/dt or any other hemodynamic parameter. The infusion of vitamin C augmented the LV ϩdP/dt response to dobutamine by 22Ϯ4% (Dob, 1680Ϯ76 mm Hg/s; Dobϩvit C, 1814Ϯ97 mm Hg/s, PϽ0.01). In the control group (nϭ9), LV ϩdP/dt was measured in response to sequential infusions of dobutamine (Dob, Dob-2) given at the same time intervals as in the experimental group but without the intracoronary infusion of vitamin C. In contrast to the experimental group, no difference in LV ϩdP/dt was observed between the 2 infusions of dobutamine (Dob, 1706Ϯ131 mm Hg/s; Dob-2, 1709Ϯ138 mm Hg/s, PϭNS). Conclusions-The administration of the antioxidant vitamin C augments the inotropic response to dobutamine in humans.This suggests that redox environment contributes to the adrenergic regulation of ventricular contractility.

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Section: Discussionsupporting

confidence: 79%

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

Mak

Newton

2001

Circulation

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“…The absence of an atropine effect on cardiac sympathetic activity in subjects with CHF is consistent with previous observations that have documented that heart failure represents a state of parasympathetic withdrawal. 5,6,18 This is known to occur at the level of the sinus node, 27 and our laboratory has recently confirmed decreased parasympathetic input to the failing human left ventricle. 18 These observations, taken together, suggest that abnormalities in cardiac parasympathetic tone may be one factor that contributes to the increase in cardiac sympathetic activity seen in the setting of CHF.…”

Section: Azevedo and Parker Muscarinic Control Of Cardiac Sympatheticmentioning

confidence: 69%

“…This does not appear to be the case, because in a previous report we have demonstrated that the same estimated intracoronary concentration of atropine completely inhibited the hemodynamic effects of acetylcholine. 18 Because this concentration of acetylcholine also caused potent inhibitory effect on cardiac sympathetic activity in the CHF group, we believe that the dose of atropine used was adequate to provide blockade of myocardial muscarinic receptors.…”

Section: Azevedo and Parker Muscarinic Control Of Cardiac Sympatheticmentioning

confidence: 94%

“…The sequence of infusions was as follows: 1) D 5 W was infused intracoronary at the rate of 1.25 mL/min, 2) atropine was infused at a rate of 12 g/min. 18 We did not attempt to recontrol for the results of atropine because this drug has a half-life Ͼ2 hours. 19 All drugs were infused into the left main coronary artery via a 7F Judkins catheter using a Harvard infusion pump.…”

Section: ϫ5mentioning

confidence: 99%

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Parasympathetic Control of Cardiac Sympathetic Activity

Azevêdo

Parker

1999

Circulation

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Background-Muscarinic receptors on adrenergic nerve terminals attenuate norepinephrine release. The role of these receptors in the modulation of cardiac norepinephrine release in humans remains uncertain. Methods and Results-Twelve patients with normal left ventricular (LV) function and 18 with congestive heart failure (CHF) were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) in response to intracoronary acetylcholine (ACh, 5ϫ10 Ϫ5 Mol), and in response to intracoronary atropine (12 g/min). ACh did not affect CANESP in the group of subjects with normal LV function, but it caused a significant reduction in those with CHF [197 (150 to 302) Conclusions-Therefore, in the setting of heart failure and sympathetic activation, muscarinic receptor stimulation decreases CANESP, an effect not observed in patients with preserved LV function. Blockade of muscarinic receptors with atropine increased CANESP in patients with normal LV function, suggesting that cardiac parasympathetic tone has inhibitory effects on cardiac sympathetic activity. This basal inhibition was not observed in CHF patients in response to atropine. The lack of basal parasympathetic inhibition of cardiac sympathetic activity may play a role in the pathogenesis of cardiac sympathetic activation in heart failure. (Circulation. 1999;100:274-279.)

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“…Congestive heart failure (HF), a disease with high mortality and increasing prevalence, 1 is characterized by autonomic imbalance, including decreased parasympathetic tone, 2,3 hyperactive sympathetic tone 4,5 and impaired baroreflex control of sympathetic activity. 6,7 Pharmacotherapy attempting to restore the autonomic imbalance with drugs such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and aldosterone receptor antagonists have been shown to improve survival among HF patients and are recommended for HF patients with reduced ejection fraction.…”

Section: Introductionmentioning

confidence: 99%

Interventional and Device-Based Autonomic Modulation in Heart Failure

Shen¹,

Zipes²

2015

Heart Failure Clinics

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Abstract/SummaryHeart failure is an increasingly prevalent disease with high mortality and public health burden. It is associated with autonomic imbalance characterized by sympathetic hyperactivity and parasympathetic hypoactivity. Evolving novel interventional and device-based therapy has sought to restore autonomic balance by neuromodulation.Results of preclinical animal studies and early clinical trials have demonstrated its safety and efficacy in heart failure. In this review article, we will discuss specific neuromodulatory treatment modalities individually-spinal cord stimulation, vagus nerve stimulation, baroreceptor activation therapy and renal sympathetic nerve denervation. Key Points (3-5)• Heart failure (HF) is a disease categorized by sympathetic hyperactivity, parasympathetic withdrawal and impaired baroreflex control of sympathetic activation.• Several measures of autonomic modulation either by implanted devices or interventions seek to restore the autonomic balance in HF and improve outcomes. These measures include spinal cord stimulation, vagus nerve 3 stimulation, baroreceptor activation therapy and renal sympathetic nerve denervation.• Preclinical work and the majority of early clinical trials demonstrate the benefits of these modalities in HF. Additional larger, well-designed, outcome-based clinical trials are warranted to verify the results and determine whether these evolving, innovative neuromodulation approaches can be recommended to the growing population of HF patients.4

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Muscarinic receptor modulation of basal and beta-adrenergic stimulated function of the failing human left ventricle.

Cited by 50 publications

References 36 publications

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

Parasympathetic Control of Cardiac Sympathetic Activity

Interventional and Device-Based Autonomic Modulation in Heart Failure

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