Vagal blockade

The reflex nature of the bradycardia induced by parenterally administered norepinephrine can readily be demonstrated by administration of atropine, a choli-noreceptor antagonist. Atropine abolishes the compensatory vagal reflexes. Under conditions of vagal blockade, the direct cardiac stimulatory effects of norepinephrine are unmasked. There is marked tachycardia, an increase in stroke volume, and as a consequence, a marked increase in cardiac output (Fig. 10.4). 

Sinus tachycardia (due to vagal blockade) is a common feature but abnormalities of cardiac conduction accompany moderate to severe intoxication and may proceed to dangerous tachy- or bradyarrhythmias. Hypoterrsion may result from a combination of cardiac arrhythmia, reduced myocardial contractility and dilatation of venous capacitance vessels. 

Cardiovascular adverse effects are minimal with pancuronium. Ganglion blockade does not occur. Shght dose-dependent rises in heart rate, blood pressure, and cardiac output are common (5), but are often masked by the actions of other co-administered agents, such as fentanyl or halothane, which cause bradycardia or hypotension. These adverse effects of pancuronium are thus often beneficial and can be deliberately harnessed. Several mechanisms contribute vagal blockade via selective blockade of cardiac muscarinic receptors (6), release of noradrenaline from adrenergic nerve endings (7), increased blood catecholamine concentrations (8), inhibition of neuronal catecholamine reuptake (9-11), and direct effects on myocardial contractility (12). These have been reviewed (13-15). 

Fig. 10. Effects of vagal blockade on gastrointestinal contractions induced by (A) EM574 and (B) motilin. The period of bilateral vagal blockade is indicated by an unbroken bar and that of unilateral vagal blockade by a dashed bar. Bilateral blockade inhibited gastrointestinal contractions induced by EM574 (3 pg/kg hr ) and motilin (1 pg/kg hr ). After increasing the doses of EM574 and motilin, strong contractions were induced. Unilateral vagal blockade did not affect motilin-induced contractions. (From Inatomi et al. [15] with permission of the editor.)...

The compound atropine has been shown to rapidly cross the placenta (Kanto et al. 1981 Kivalo and Saarikoski 1977 Onnen et al. 1979) and has been used to test placental function in high-risk obstetric patients by producing fetal vagal blockade and subsequent tachycardia (Heilman and Fillisti 1965). Atropine has also been used to reduce gastric secretions before cesarean section with no fetal or neonatal effects observed (Diaz et al. 1980 Roper and Salem 1981). 

De Troyer A, Yernault JC, Rodenstein D. Effects of vagal blockade on lung mechanics in normal man. J Appl Physiol 1979 46 217-226. 

The first study was performed at the University of Bonn, Germany. The purpose of the experiment was to study the cardiovascular effects of vagal blockade during the performance of a mental loading task. In this chapter, however, only data of the preblockade part of the experimental session are described. A comparison is made between a baseline (rest) period (5 minutes) and a task period (5 minutes) in which participants had to perform a memory search and counting task. The results of this study are summarized in Fig. 6.2. For details, see van Roon (1998). 

Selective 5-HT3 receptor antagonists have potent antiemetic properties that are mediated mainly through peripheral 5-HT3 receptor blockade on intestinal vagal afferents. In addition, central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone probably plays an important role. The antiemetic action of these agents is restricted to emesis attributable to vagal stimulation other emetic stimuli such as motion sickness are poorly controlled. 

Data analysis is done by the method of Litchfield and Wilcoxon. Mean dose - response curves are plotted on log-probit paper. Best fit to straight lines on these scales is determined by computerized regression. The cumulative ED50 values for vagal and sympathetic inhibition and the cumulative ED95 values for neuromuscular blockade are determined from the lines and 95 % confidence limits are calculated. Differences in potency are considered significant when P < 0.05. 

The autonomic margins of safety of the test drugs are calculated as the ratios of cumulative doses producing 50 % block (ED50) of vagal (parasympathetic) and sympathetic transmission and the ED50 for histamine release, each divided by the ED50 of neuromuscular blockade. 

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