Typical vasovagal syncope as a "defense mechanism" for the heart by contrasting sympathetic overactivity.

Many observations suggest that typical (emotional or orthostatic) vasovagal syncope (VVS) is not a disease, but rather a manifestation of a non-pathological trait. Some authors have hypothesized this type of syncope as a "defense mechanism" for the organism and a few theories have been postulated. Under the human violent conflicts theory, the VVS evolved during the Paleolithic era only in the human lineage. In this evolutionary period, a predominant cause of death was wounding by a sharp object. This theory could explain the occurrence of emotional VVS, but not of the orthostatic one. The clot production theory suggests that the vasovagal reflex is a defense mechanism against hemorrhage in mammals. This theory could explain orthostatic VVS, but not emotional VVS. The brain self-preservation theory is mainly based on the observation that during tilt testing a decrease in cerebral blood flow often precedes the drop in blood pressure and heart rate. The faint causes the body to take on a gravitationally neutral position, and thereby provides a better chance of restoring brain blood supply. However, a decrease in cerebral blood flow has not been demonstrated during negative emotions, which trigger emotional VVS. Under the heart defense theory, the vasovagal reflex seems to be a protective mechanism against sympathetic overactivity and the heart is the most vulnerable organ during this condition. This appears to be the only unifying theory able to explain the occurrence of the vasovagal reflex and its associated selective advantage, during both orthostatic and emotional stress.

Vasovagal Syncope As A Manifestation Of An Evolutionary Selected Trait.

Some observations suggest that typical (emotional or orthostatic) vasovagal syncope (VVS) is not a disease, but rather a manifestation of a non-pathological trait. We conducted an extensive bibliographic research on the vasovagal reactions in animals, including humans, in order to investigate the possible factors that may explain the origin and evolution of VVS. We found two processes which appear relevant for the investigation of VVS evolution: fear/threat bradycardia (alarm bradycardia) in animals, mainly during tonic immobility and vasovagal reflex during hemorrhagic shock (thoracic hypovolemia) both in animals and humans. The available data suggest that VVS in humans, alarm bradycardia in animals and the vasovagal reflex during hemorrhagic shock share the same physiological mechanisms and that is indicative of a common evolutionary root. However, during the vasovagal reflex loss of consciousness occurs in humans, but it is absent (or extremely rare) in animals. That can be explained as a by-product due to the erect position and the large brain evolved in our species. If the vasovagal reflex persisted for millions of years along the vertebrates evolutionary history, we can reasonably assume that it has a function and it is not harmful. It could be neutral or beneficial, but the available data suggest it is beneficial; likely, it evolved as an advantageous response to stressful and possibly dangerous heart conditions. Emotional or orthostatic vasovagal reflex is preceded by enhanced sympathetic activity, which is harmful and possibly dangerous. The transient inhibition of the sympathetic system, together with activation of the vagal tone , characterizes VVS. The consequent slowing of the heart rate induced by the vasovagal reflex may constitute a beneficial break of the cardiac pump, thereby reducing myocardial oxygen consumption. We suggest that typical VVS should be regarded as a selected response, which probably evolved in the ancient past as a defense mechanism of the organism within some ancestral group(s) of vertebrates.

Diving bradycardia: a mechanism of defence against hypoxic damage.

A feature of all air-breathing vertebrates, diving bradycardia is triggered by apnoea and accentuated by immersion of the face or whole body in cold water. Very little is known about the afferents of diving bradycardia, whereas the efferent part of the reflex circuit is constituted by the cardiac vagal fibres. Diving bradycardia is associated with vasoconstriction of selected vascular beds and a reduction in cardiac output. The diving response appears to be more pronounced in mammals than in birds. In humans, the bradycardic response to diving varies greatly from person to person; the reduction in heart rate generally ranges from 15 to 40%, but a small proportion of healthy individuals can develop bradycardia below 20 beats/min. During prolonged dives, bradycardia becomes more pronounced because of activation of the peripheral chemoreceptors by a reduction in the arterial partial pressure of oxygen (O2), responsible for slowing of heart rate. The vasoconstriction is associated with a redistribution of the blood flow, which saves O2 for the O2-sensitive organs, such as the heart and brain. The results of several investigations carried out both in animals and in humans show that the diving response has an O2-conserving effect, both during exercise and at rest, thus lengthening the time to the onset of serious hypoxic damage. The diving response can therefore be regarded as an important defence mechanism for the organism.

Simultaneous occurrence of two independent vagal reflexes: a possible cause of vagal sudden death.

A vagal origin of sudden death has been hypothesised in humans, but it has not yet been clearly demonstrated. Two vagal reflexes have been widely investigated: the diving reflex and the fear-induced central reaction, which are responsible for diving bradycardia and alarm bradycardia, respectively. The latter occurs in humans mainly in the context of emotional presyncope/syncope. A simultaneous occurrence of these two vagal reflexes has been observed in animals that are threatened while diving, and heart rates (HR) as low as two to six beats/min have been reported. In experiments carried out in rats, a high percentage of animals that were stressed before immersion in water died suddenly due to progressive slowing of HR; autopsy revealed no signs of drowning. No animals died if they had not been previously stressed. These data show that vagal sudden death can occur when the vagal cardiac fibres are synergically stimulated by two independent reflexes. In humans, it has been reported that in 10-15% of people who die after falling into water, autopsy reveals little or no water in the lungs. These sudden deaths could be due to vagal overactivity. The development of an adequate laboratory model may improve knowledge of the pathophysiology of this type of vagal sudden death and of its prevention.

[Origin and evolution of vasovagal syncope]. / Origine ed evoluzione della sincope vasovagale.

Vasovagal syncope (VVS) is characterized by sudden hypotension and bradycardia, due to inhibition of the sympathetic system and activation of the vagal system, respectively. Major lines of evidence suggest that classical (emotional and orthostatic) VVS is not a disease, but a characteristic of the individual. It is, therefore, interesting to investigate the factors that can explain its origin and evolution and, to this purpose, we investigated the available literature data on the vasovagal reflex in animals, including humans. We found two processes in vertebrates, which appear relevant to the investigation of VVS evolution: fear and threat bradycardia in animals and vasovagal reflex during hemorrhagic shock, both in animals and humans. The trigger of the latter is thoracic hypovolemia, the same of the vasovagal reflex occurring in humans during orthostatic stress (prolonged standing, tilt testing). During thoracic hypovolemia, the vasovagal reflex in humans seems to share physiological mechanisms similar to those observed in other mammals, that is an activation of the vagal system and an inhibition of the sympathetic system, preceded by an activation of the same system. Even emotional VVS in humans seems to share physiological mechanisms similar to those observed in other vertebrates during fear/threat bradycardia. Therefore, the vasovagal reflex appears to be predisposed in humans and other vertebrates with the same mechanisms and this may indicate a common evolutionary root. If the vasovagal reflex persisted for millions of years along the vertebrates evolutionary history, we can reasonably assume that it has (or it maybe had in the past) a function. Also, since this reflex is sporadically displayed, a role as a "defense mechanism" appears likely. The most likely hypothesis is a defense mechanism of the heart during stressful and possible dangerous heart conditions. The slowing of heart rate induced by the vasovagal reflex may constitute a beneficial break of cardiac pump (thereby reducing myocardial oxygen consumption) and permit better diastolic filling and coronary perfusion.

The origin of vasovagal syncope: to protect the heart or to escape predation?

Major lines of evidence suggest that classical (emotional and orthostatic) vasovagal syncope (VVS) is not a disease, but rather a manifestation of a non-pathological trait. It is, therefore, reasonable to investigate the possible factors that may explain its origin and evolution. We reviewed the data available in the literature on the vasovagal reaction in humans and animals in order to identify possible similarities that might provide insight into the evolution of VVS. We found two processes which appear relevant to the investigation of VVS evolution: fear and threat bradycardia in animals, and the vasovagal reflex during hemorrhagic shock in humans and animals. We suggest that VVS in humans involves physiological mechanisms similar to those found in other vertebrates, and that this may indicate a common evolutionary root. The available data seem to suggest that VVS evolved as an advantageous response to inescapable predators or to stressful and possibly dangerous heart conditions. The inhibition of the sympathetic system, together with activation of the vagal system, characterizes VVS. The consequent slowing of the heart rate induced by VVS may constitute a beneficial break of the cardiac pump, thereby reducing myocardial oxygen consumption. We suggest that classical VVS did not evolve recently in the modern human lineage; rather, it should be regarded as a selected response, which probably evolved in the ancient past as a "defense mechanism" of the organism within some ancestral group(s) of vertebrates.

[Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models]. / I fattori psicosociali quali predittori di aterosclerosi e di eventi cardiovascolari: contributi da modelli animali.

Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been investigated. As regards the biological mechanisms of chronic stress, the hypothalamic-pituitary-adrenal axis and the sympathetic system have been investigated. The studies have mainly been carried out on primates, and, to a less extent, on other mammals such as rabbit and wolf and on some species of birds. In the animals under social isolation, subordination or hostility/anger, a significantly more severe atherosclerosis was present, besides an increased activity of the hypothalamic-pituitary-adrenal axis and sympathetic system. In conclusion, the results offered by animal models seem to satisfy the first of Kuller's criteria, as for the three above-mentioned psychosocial factors.