Effects of acetylcholine on the ventricular specialized conducting system of neonatal and adult dogs.

Danilo, Peter; Rosen, Michael R.; Hordof, Allan J.

doi:10.1161/01.res.43.5.777

Cited by 38 publications

(8 citation statements)

References 15 publications

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“…First, in addition to the dominant cardiac cholinergic (muscarinic) M2 receptor found in the adult heart, M1 subtypes may be found in the neonatal heart (43). These neonatal receptors may serve different physiologic responses to acetylcholine stimulation (44). Second, parasympathetic activity can modulate sympathetic effects by inhibiting norepinephrine release and modulating the sympathetic system (45).…”

Section: Autonomic Function In Preterm Infantsmentioning

confidence: 99%

Cardiovascular Autonomic Regulation in Preterm Infants: The Effect of Atropine

et al. 2004

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To study cardiovascular autonomic control, we assessed the effect of atropine on heart rate (HR) and blood pressure (BP) variability in 12 preterm infants (range 26 -32 wk) before intubation for respiratory insufficiency. Spectral power analysis of R-R interval and systolic BP (SBP) series were estimated in a low-frequency (LF; 0.04 -0.15 Hz) and high-frequency (HF; 0.4 -1.5 Hz) band and evaluated for a 10-min period before and a 10-min period after atropine sulfate (0.01 mg/kg). Baroreceptor reflex (BR) functioning was estimated using transfer function analysis at LF (coherence, gain, and phase). Atropine resulted in a significant 12% increase in steady-state HR (p Ͻ 0.01) and unchanged SBP. For R-R interval series, the total spectral power decreased 6-fold (p Ͻ 0.01), which was predominantly due to a reduction in the LF band (16-fold; p Ͻ 0.01). In contrast, we observed a significant increase (25%; p Ͻ 0.05) in total spectral power of SBP series partly as a result of an increase in HF power. The LF power of SBP series was not altered. The median LF transfer gain (BR sensitivity) between SBP and R-R interval decreased from 4.2 to 1.4 ms/mm Hg (p Ͻ 0.01) after atropine. The LF phase relationship (BP leads R-R interval fluctuations bỹ 4 s) was not changed after atropine. In conclusion, even in preterm infants in distress, atropine modulates HR and BP variability, suggesting that BR-mediated parasympathetic control of heart rate is of significance for cardiovascular control at that age. The baroreceptor reflex (BR) is the most important regulatory mechanism in the short-term control of heart rate (HR) and blood pressure (BP). The BR buffers sudden changes in systemic BP by adapting HR and peripheral vascular resistance. These responses of HR and vascular resistance are mediated by the efferent parasympathetic and sympathetic limb of the BR. As both systems are involved, studies on the BR give information on autonomic cardiovascular regulation (1,2).Data about the ontogeny of the BR and functional maturation in the human infant are limited. This is partly caused by the limited experimental (pharmacologic or mechanical) possibilities to challenge the BR in neonates. Passive head-up tilt test has been applied to neonates to measure responses in BP, HR, and limb blood flow to body tilting. In preterm infants (26 -38 wk gestation), passive head-up tilt resulted in significant vasoconstriction of the lower limb with a slight fall in aortic BP and unchanged HR (3). The inadequate ability to maintain BP and the lack of tachycardia suggest that preterm infants lack the full integrated BR response as seen in adults. In term infants, however, a fall in systolic BP (SBP) was observed in conjunction with tachycardia and a fall in limb blood flow, suggesting the presence of active reflex vasoconstriction (4). In a recent study, BR maturation was studied longitudinally in preterm infants, using a beat-to-beat analysis of R-R interval series and noninvasively measured SBP (5). BR sensitivity (the R-R interval change in millisecon...

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Section: Autonomic Function In Preterm Infantsmentioning

confidence: 99%

Cardiovascular Autonomic Regulation in Preterm Infants: The Effect of Atropine

et al. 2004

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“…However, there are conflicting data regarding the importance of direct vagal effects in the ventricular myocardium and the HPS. Several studies have shown that vagal stimulation and ACh infusion exert a negative chronotropic effect on His-Purkinje tissues in vitro and in vivo (52,(60)(61)(62)(63). In addition, ventricular refractory periods are shortened in response to atropine in patients pretreated with propranolol, suggesting a direct cholinergic effect in this tissue (64).…”

Section: Autonomic Effects On the Hpsmentioning

confidence: 99%

Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

Lerman¹,

Wesley²,

DiMarco³

et al. 1988

J. Clin. Invest.

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The effects of adenosine on the human His-Purkinje system (HPS) were studied in nine patients with complete atrioventricular (AV) block. Adenosine had minimal effect on the control HPS cycle length, but in the presence of isoproterenol increased it from 906±183 to 1,449±350 ms, P < 0.001. Aminophylline, a competitive adenosine antagonist, completely abolished this antiadrenergic effect of adenosine.In isolated guinea pig hearts with surgically induced AV block, isoproterenol decreased the HPS rate by 36%, whereas in the presence of 1,3-dipropyl-8-phenyl-xanthine, a potent adenosine antagonist, the HPS rate decreased by 48% and was associated with an increased release of adenosine. Therefore, by blocking the effects of adenosine at the receptor level, the physiologic negative feedback mechanism by which adenosine antagonizes the effects of catecholamines was uncoupled.The results of this study indicate that adenosine's effects on the human HPS are primarily antiadrenergic and are thus consistent with the concept of accentuated antagonism. These effects of adenosine may serve as a counterregulatory metabolic response that improves the 02 supply-demand ratio perturbed by enhanced sympathetic tone. Some catecholaminemediated ventricular arrhythmias that occur during ischemia or enhanced adrenergic stress may be due to an imbalance in this negative feedback system.

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“…In addition, carotid sinus massage does not allow stable slow rates, but rather, prolonged pauses of unpredictable length with no possible control of the preceding cycle length. Another problem is the possibility that the liberation of acetylcholine might eventually alter some of the variables under study.29 31 Nevertheless, vagal stimulation is the most accessible way of slowing instantaneously the heart rate in the human, and the proposed model, despite its limitations, is practically the only manner of studying the effects of drugs on In addition to its theoretical interest regarding the mechanisms of tachycardia-and bradycardia-dependent block, our study suggests that isoproterenol may be useful in some patients with left BBB in which there is a need to observe the normally conducted QRS pattern, in patients in whom a complete interruption of conduction in one of the bundle branches must be ascertained, and in patients in whom phase 4 block is suspected. …”

Section: Effects On Refractoriness and Conductionmentioning

confidence: 99%

Effects of isoproterenol on abnormal intraventricular conduction.

Halpern¹,

Chiale²,

Nau³

et al. 1980

Circulation

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SUMMARY An isoproterenol infusion (1.0-4.0 ,ug/min) was administered to 15 patients with intermittent bundle branch block (BBB) and two patients with apparently fixed BBB. Three main effects were documented: (1) In all patients with phase 3, or tachycardia-dependent, BBB, isoproterenol caused a pronounced shortening of refractoriness in the affected fascicle. (2) In patients showing phase 4, or bradycardia-dependent, BBB, isoproterenol prolonged the phase 4 block range, probably because of enhanced diastolic depolarization. In one patient (four studies) in whom phase 4 block was not present, isoproterenol caused the appearance of a phase 4 block range. (3) In the two patients with fixed BBB, isoproterenol restored conduction, probably as a result of a hyperpolarizing effect. This study shows that isoproterenol tends to restore or improve conduction related to tachycardia-dependent block, but may impair conduction related to bradycardia-dependent block. dependent BBB is favored or provoked, probably through an enhancement of diastolic depolarization.Materials and Methods Fifteen patients with intermittent BBB were studied. Carotid sinus massage was performed in every case during a continuous ECG recording to document the existence and measure the extension of a phase 3 and phase 4 block range. The 15 cases were selected from a much larger series of patients with intermittent BBB and entered the study only when the maneuvers were effective in uncovering these conduction ranges, or in separating a phase 3 block range from a normal conduction range. Two patients who apparently had permanent or rate-independent BBB, but who were known to have intermittent BBB a few weeks before, were also included. During the vagal stimulation, junctional and ventricular escapes were sometimes documented. After this control study, carotid sinus massage was repeated during and after the administration of an i.v. drip of isoproterenol, for which 1 mg of the drug was dissolved in 500 ml of isotonic glucose solution. The infusion was started at a rate of 1 ,ug/min of isoproterenol during 5-10 minutes; if no significant changes in conduction were observed, the rate of infusion was raised in successive steps of 1 gg/min during 5-10 minutes; the infusion was interrupted either when clear changes in conduction were seen or when changes did not occur after the infusion of 4 ,ug/min, or when ventricular arrhythmias developed at any time (the latter occurred only in one patient, who was then excluded from the study). When conduction changes were observed, the vagal stimulation was repeated after the infusion, until the recorded changes returned to the control condition. All the tracings were recorded on a Sanborn direct-writing two-channel machine and conventional measurements were made to determine the variations in cardiac rate and extension of the conduction ranges, as well as in the coupling interval of the escape beats. The statistical significance of the results was assessed using the paired t test. Thirteen patients were studied only 135...

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Effects of acetylcholine on the ventricular specialized conducting system of neonatal and adult dogs.

Cited by 38 publications

References 15 publications

Cardiovascular Autonomic Regulation in Preterm Infants: The Effect of Atropine

Cardiovascular Autonomic Regulation in Preterm Infants: The Effect of Atropine

Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

Effects of isoproterenol on abnormal intraventricular conduction.

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