Search

Carotid sinus massage for diagnosis and termination of supraventricular tachycardia (SVT) is still a widely used vagal manoeuvre in the AE department. However, itsefficacy is limited (termination of the SVT in approximately 20%) and carotid sinus massage may be complicated by (potentially devastating) neurologic complications in 0.2-1% of the patients. There are safer interventions without neurologic complications, such as the modified Valsalva manoeuvre (efficacy 43%) and intravenous administration of adenosine (efficacy 75%). Monitor observation of the heart rhythm is required, both for vagal manoeuvres and for adenosine administration, because of the possibility of ventricular tachycardia or ventricular fibrillation induction (incidence 0.08%). Carotid sinus massage remains an important diagnostic method in patients with unexplained syncope in whom, based on the clinical history, carotid sinus hypersensitivity is suspected. It should be avoided in patients with previous TIA or stroke within the past 3 months, or those with carotid bruits, except if carotid Doppler studies have excluded significant stenosis (≥ 70%).

Keywords: blood pressure, cardiac output, muscle pump, orthostatic hypotension, syncope, venous return.IntroductionStanding upright challenges the cardiovascularsystem as the pull of gravity displaces about 70%of the circulating blood volume to below heart level,much of it to the compliant veins of the dependentlimbs and the pelvic organs. In patients withautonomic failure due to neurodegenerative dis-eases, the normal cardiovascular adjustments tothis challenge are impaired, and symptomaticorthostatic hypotension becomes a common riskon standing or even sitting quietly. These patientslearn to sway and shift, so that the pumping actionof the muscles can be utilized to counter gravita-tional displacement of blood by squeezing venousblood from the legs upward. Augmentation ofvenous return in the upright posture can also beachieved by deliberate tensing of lower limb andabdominal muscles [1, 2], as depicted in Fig. 1.These clinical observations were the basis forphysical countermeasures, which are taught topatients with autonomic failure to combat symp-tomatic orthostatic hypotension [3–5]. Physicalcounterpressure manoeuvres specifically generatea counterpressure to oppose gravitational venouspooling (e.g. a single bout of lower-body musclecontraction to translocate blood centrally andsustained tensing of the same muscles to preventsubsequent peripheral pooling in the legs andabdomen). More recently, it has been shown thatphysical counterpressure manoeuvres are alsoeffective interventions in otherwise healthy sub-jects with episodic orthostatic syncope due toneurally mediated (i.e. vasovagal reactions) [6, 7]or postexercise syncope [8].In this narrative review, we will primarily considerthese physical counterpressure manoeuvres. Sec-ondarily, we will describe the broader category ofphysical countermeasures that include breathingmanoeuvres and other physical methods, tooppose orthostasis. Existing external devices,which operate through some of the same physio-logical principles as these manoeuvres, will only bediscussed for proof of principle.The defining characteristic of the manoeuvresdescribed in this review is the fact that they canbe employed by patients when a faint is imminent.This is in contrast to devices such as bandages andabdominal belts, which require ongoing use to beeffective. We will discuss both early studies inpatient with primary autonomic failure due toneurodegenerative diseases, as well as more recentexperience obtained in patients with neurally med-iated syncope. The physiology and pathophysiologyof orthostatic blood pressure control and perfusionof the brain are key factors in understanding howphysical countermeasures work. These topics havebeen reviewed extensively [2, 9–12] and will only bediscussed here briefly.Physical counterpressure manoeuvresMuscle tensingIt has been reported that intramuscular pressure isrelated to orthostatic tolerance [2]. Hendersonet al. demonstrated that intramuscular pressuremeasured in the relaxed biceps muscle wasdecreased after prolonged bed rest (38%), followingsurgery (35%), during voluntary hyperventilation(28%) and in the absence of air movement over theskin (31%) [13, 14]. These conditions are stronglyassociated with decreased orthostatic toleranceand a tendency to faint [2, 15]. In addition,intramuscular calf pressure has been shown tobe 15–24 and 6–9 mmHg, respectively, in thosewithout and with a tendency to faint during thehead-up tilt test using a tilt table with a saddle andsuspended legs (Fig. 1) [16].Although these interesting results from studiesperformed in the 1930s and early 1940s have

Orthostatic gravitational stress results in a decrease in venous return. Because the heart cannot pump blood that it does not receive, ventricular stroke volume and cardiac output decline, but until the point of presyncope, there is little change in arterial pressure. There is little doubt that the vasomotor outflow to the resistance vessels and presumably the splanchnic capacitance vessels are of fundamental importance in the prevention of hypotension (Rowell, 1993; Wieling and van Lieshout, 2008), but there is also a concomitant increase in heart rate and the significance of this is much less clear (Hainsworth, 2000). In a recent issue of Frontiers in Physiology, Convertino focussed on the physiology of maximal compensation to orthostasis studying high and low tolerant healthy subjects. Exposure to a maximal lower body negative pressure (LBNP) test was used to quantify orthostatic tolerance. The author argues that this stressor is equivalent to actual orthostasis. However, recent studies suggest that pooling in the splanchnic area during actual orthostasis (standing/head-up tilting) is more important than previously reported in studies using simulated orthostasis by applying lower-body negative pressure up to the levels of the iliac crest (Taneja et al., 2007). More pronounced splanchnic pooling during orthostasis may result in more stimulation of vascular subdiaphramatic receptors that are postulated to play a role in orthostatic adjustment by causing vasoconstriction and augmentation of the carotid baroreflex (Doe et al., 1996). Other obvious differences with LBNP are that during free standing the carotid baroreceptors are always above the heart and the static increase in skeletal muscle tone during active standing opposes pooling of blood in limb veins (Wieling and van Lieshout, 2008; Wieling et al., 2014). Increases in skeletal muscle tone are a key factor in orthostatic adjustment. Accordingly, a static increase in skeletal muscle tone by leg-crossing during a maximal LBNP test increases time to presyncope considerably (Krediet et al., 2006). Therefore, a device which combines head-up tilting with negative pressure to the lower part of the body (Hainsworth, 2000) seems a more physiological approach to quantify orthostatic tolerance in a reproducible way. Although LBNP (in the horizontal position) is a deficient model for studying orthostasis, it can be used to simulate loss of central blood volume (hemorrhage) (Johnson et al., 2014). As far as the physiology of maximal hemodynamic compensation in high and low tolerant healthy subjects, the author reaffirms the concept that the heart rate response contributes significantly to orthostatic tolerance (Convertino, 2014). The observations of Convertino are of considerable interest, but it important to realize that they are based on studies in young adult healthy subjects exposed to a maximal LBNP stress. The observations cannot be generalized to the adjustment to the upright posture during free standing. Based on clinical observations the following data indicate that neural heart rate control is not important for orthostatic tolerance. Weissler studied the effects of posture and atropine on the cardiac output in six young adult male subjects. He documented that atropine administered in the supine position increased heart rate on average by 44 beats/min. The heart rate increase was accompanied by a cardiac output rise of about a factor 2 with an increase in mean arterial pressure. After administration of atropine in the upright posture heart rate increase by 65 beats/min, but no effect on cardiac output and blood posture were observed. When pooling of blood in the upright posture was prevented by sustained inflation of an anti-gravity suite, the cardiac responsiveness to atropine in tilted subjects was restored, in part (Weissler et al., 1957a). In another study it was documented that administration of atropine could not prevent an impending vasovagal faint (Weissler et al., 1957b). Patients with a cardiac transplants have no increase in heart rate on standing, but intact orthostatic blood pressure control (Figure ​(Figure1,1, left panel) (Van Lieshout et al., 1989; Wieling and Karemaker, 2013). Figure 1 Blood pressure and heart rate responses induced by active standing in a 38 year-old fit patient with a cardiac transplant (left panel) and a 23-year-old female patient with orthostatic hypotension (hypoadrenergic) with intact heart rate control (right ... In patients with sympathetic vasomotor lesions, but intact vagal heart rate control pronounced orthostatic hypotension occurs despite an impressive postural tachycardia (Figure ​(Figure1,1, right panel) (Wieling and Karemaker, 2013). Atrial tachypacing at best has marginal effects on hypotension in patients with severe orthostatic hypotension due to autonomic failure (Sahul et al., 2004) and cardiac pacing does not improve orthostatic tolerance in patients with vasovagal syncope (El-Bedawi et al., 1994). However, benefit from rate-drop pacing in older patients with documented prolonged asystolic syncope has been reported (Brignole et al., 2012). Another example of the disconnect between the heart rate responses and orthostatic tolerance are patients with the postural orthostatic tachycardia syndrome in whom very high orthostatic heart rates are associated with orthostatic presyncope. The treatment in these patients is aimed at decreasing postural complaints by decreasing the postural tachycardia (Joyner, 2011). These data strongly support the view that the central venous reservoir is an important determinant of cardiac responsiveness to changes in heart rate i.e., a heart cannot pump blood that it does not receive. In fact, very high heart rates would decrease cardiac filling time and during conditions of impaired venous return such as orthostatic stress, could actually impair cardiac output (Hainsworth, 2000). The positive correlation between orthostatic tolerance and the maximal sympathetically mediated heart rate before syncope in high and low tolerant healthy subjects observed by Convertino may have been because in this situation heart rate is a marker for enhanced sympathetic drive to resistance vessels, which provide the main defense against hypotension (Rowell, 1993; Hainsworth, 2000). In conclusion, The arterial (and especially carotid) baroreceptor control of sympathetic motor tone of resistance and splanchnic capacitance vessels in combination with the central blood volume are the most important components in the maintenance of postural normotension in humans (Rowell, 1993; Wieling and van Lieshout, 2008). Activation of the skeletal muscle pump in the lower body can compensate in part for defects in control of vasomotor tone and a reduction of central blood volume. Cardiac effector mechanisms appear not to be important for the adjustment of arterial pressure to the upright posture.

The aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well-established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnose CSH are too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitory CSH (asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients with CSH should be thought of as being 'mixed', between cardioinhibition and vasodepression. The proposed stricter set of criteria for CSH should be evaluated in future studies.

In order to endow virtual agents with more realistic affective behavior, it is important to provide them not only the capability to generate and regulate emotions, but also the ability to reason about the emotion regulation processes of other agents. To this end, this paper introduces a computational model for a theory of emotion regulation (ToER). The model has been implemented and tested using the modeling language LEADSTO. In addition, a virtual environment application has been developed, which is inhabited by agents that are equipped with the model for ToER. A first evaluation indicates that the model indeed enables the agents to show more realistic affective behavior.