THE idea that reflexes originating in the heart can play a role in normal physiology dates to the 1860s. 1Until the 1950s, these reflexes, and the Bezold–Jarisch reflex (BJR) in particular, were regarded largely as pharmacological curiosities with the only practical application of the study of the BJR being the clinical use of a veratrum alkaloid as an antihypertensive agent. Since the 1860s, it had been known that injection of minute amounts (0.005 mg) of veratrine or its pure alkaloid components (veratrum) initiates a reflex which causes a rapid fall in blood pressure and heart rate in association with apnea. 1This “Von Bezold reflex” was classically defined in association with arrest of breathing, but more recently, it has been called the BJR and includes the triad of bradycardia, hypotension, and peripheral vasodilation. 2 

It is now understood that certain inhibitory reflexes, which have origin with cardiac sensory receptors, play a role in cardiovascular homeostasis. Activation of a subset of these receptors by diverse stimuli increases parasympathetic nervous system activity, inhibits sympathetic activity and is responsible for eliciting the BJR. Some anesthesiologists have suggested that the BJR may explain cardiovascular collapse reported during regional anesthesia techniques. 3–9This review focuses on the physiology of the BJR and its possible physiologic role in a number of clinical situations. It also provides discussion of the limited relevance of this reflex in regional anesthesia. The topic of clinical management will not be addressed given the paucity of data on this matter, but suggestions for future experimental direction are offered.

History of the BJR


In 1867, von Bezold and Hirt 1observed that an intravenous injection of veratrum alkaloids caused a profound decrease in blood pressure and heart rate in conjunction with apnea. In 1915, Cramer (as cited in Dawes and Comroe 2) described apnea, hypotension, and bradycardia following intravenous injection of veratrum viride extracts in cats. In the late 1930s, Jarisch and Richter 10,11studied cats in which veratridine was injected before and after interruption of the cardiac branches of the vagus nerves; they confirmed that the depressor effect initially observed in 1867 was, in fact, reflex in origin. Cramer believed that the receptors for this effect were in the lung, but Jarisch argued that the receptors were located in the ventricle of the heart. 10,11It was not until 1947 that Dawes et al. , 12using veratridine in cats, showed that the reflex apnea was caused by a mechanism separate from that mediating the hemodynamic changes. Various terms since 1867 have been used to describe these events. Today, the BJR connotes the reflex as described by Dawes in the mid twentieth century: bradycardia, vasodilation, and hypotension resulting from stimulation of cardiac receptors.

Anatomy and Physiology of the Reflex

The BJR is an inhibitory reflex usually denoted as a cardioinhibitory reflex (table 1). Early clues as to the mechanism of the BJR came from observations that cooling or sectioning the vagus nerve (the afferent limb of the reflex) could abolish the aforementioned triad of bradycardia, hypotension, and peripheral vasodilation in response to injection of veratrum alkaloids. 2Many subsequent studies have been devoted to the identification and localization of the receptors in the heart mediating this response and to defining the afferent pathways that mediate the BJR.

Table 1. Important Cardiovascular Reflexes

Table 1. Important Cardiovascular Reflexes
Table 1. Important Cardiovascular Reflexes

Afferent fibers of cardiac receptors that course in the vagus nerves are composed of two major fiber types: approximately 25% are myelinated fibers originating in the walls of the atria and in the atrial-caval junctions, and 75% are nonmyelinated fibers distributed in the walls of all cardiac chambers. 9,13,14Animal experiments using selective stimulation and interruption of nerve activity have shown that the BJR has its origin in cardiac receptors with nonmyelinated, type C vagal fibers constituting the afferent limb of the reflex. 9,15,16 

The receptors in the walls of the four cardiac chambers are the nonencapsulated terminals of the C-fiber afferents and are heterogeneous in terms of their responsiveness to mechanical (pressure, inotropism, volume) and chemical (veratrum alkaloids, adenosine tri-phosphate, serum, amidine derivatives, capsaicin and venoms from snakes, insects and marine animals) stimuli, and most respond to veratrum alkaloids, the classic pharmacologic stimulus for the BJR (fig. 1). 9,15,17–23Injection of veratrum alkaloids in the left or right coronary circulation causes not only bradycardia and a reduction in cardiac output, but also peripheral vasodilation. 2,24This is accomplished via  excitation of receptors in the cardiac wall supplied by the coronary artery.

Fig. 1. Classic activation of the Bezold–Jarisch reflex (BJR) by veratrum alkaloids. Originally characterized as a pharmacologic reflex, the BJR is activated by a variety of veratrum alkaloids. BJR activation leads to decreased vasomotor output, bradycardia, and hypotension. Hypotension and bradycardia occur in the presence of other intact reflexes, such as the baroreceptor reflex, which implies that BJR activation includes some type of inhibitory action on the baroreceptor reflex at either the afferent or efferent pathways. In this capacity, pharmacologic stimulation of the BJR makes it a dominant effector of blood pressure. In this and subsequent figures, the BJR is represented on the right  and the baroreceptor reflex on the left . The thick arrows  to the left of the text indicate change (increased or decreased activity). += activation; −= inhibition; X = abolition of that particular step; the international “no”circle  (crosshatched with line) indicates complete abolition of that pathway.

Fig. 1. Classic activation of the Bezold–Jarisch reflex (BJR) by veratrum alkaloids. Originally characterized as a pharmacologic reflex, the BJR is activated by a variety of veratrum alkaloids. BJR activation leads to decreased vasomotor output, bradycardia, and hypotension. Hypotension and bradycardia occur in the presence of other intact reflexes, such as the baroreceptor reflex, which implies that BJR activation includes some type of inhibitory action on the baroreceptor reflex at either the afferent or efferent pathways. In this capacity, pharmacologic stimulation of the BJR makes it a dominant effector of blood pressure. In this and subsequent figures, the BJR is represented on the right  and the baroreceptor reflex on the left . The thick arrows  to the left of the text indicate change (increased or decreased activity). += activation; −= inhibition; X = abolition of that particular step; the international “no”circle  (crosshatched with line) indicates complete abolition of that pathway.

The slowing of the heart is not the sole cause of the depressor response. Though the veratridine-induced bradycardia in dogs is abolished by atropine, the decrease in blood pressure is only partially attenuated. 2,25Cutting or cooling the vagus nerve has a more pronounced effect than atropine administration, veratrum alkaloid being hemodynamically benign under such conditions, 25suggesting that the BJR inhibits vasomotor output independent of heart rate modulation. These data are in accord with other evidence in cats, which also supports the idea that the BJR can independently modulate blood pressure and heart rate. 22 

Current Understanding of the Role of the BJR

Although the Veratrum alkaloids vigorously elicit the BJR, these compounds are not present in animals. The same question, therefore, that arose in the 1940s still vexes investigators today: what are the normal stimuli to these sensory nerve endings? Although not yet answered definitively, there has been great progress in our understanding of the triggering of this reflex and the role it plays in normal and abnormal circumstances (table 2).

Table 2. Possible Physiologic Roles of the Bezold–Jarisch Reflex Process Strength of Evidence

Evidence is discussed in text.

* Large body of animal and human data.

† Good animal data with some human data.

‡ Minimal animal or human data.

Table 2. Possible Physiologic Roles of the Bezold–Jarisch Reflex Process Strength of Evidence
Table 2. Possible Physiologic Roles of the Bezold–Jarisch Reflex Process Strength of Evidence

Blood Pressure Regulation

The regulation of blood pressure in normal and pathologic states is complex with multiple systems participating in maintaining hemodynamic stability. 26These multiple systems are integrated such that output from the medullary vasomotor centers (final common pathway) is tightly regulated in response to a variety of stimuli and perturbations. Vasomotor center output consists primarily of sympathetic nervous system activity and, during normal conditions, keeps blood vessels partially constricted; what is commonly referred to as vasomotor tone . Modulation of vasomotor tone is more complex than simple augmentation or attenuation of sympathetic tone. Local intrinsic regulation of arterioles (carbon dioxide, oxygen tension, and pH) combined with extrinsic vasomotor modulation, which integrates multiple systemic reflexes participate in the regulation of vascular tone.

The baroreceptor reflex (fig. 2), a primary homeostatic mechanism, includes stretch receptors in the carotid and aortic bodies whose afferent impulses are carried via  the nerve of Hering and the vagus nerve, respectively, to the medulla. Firing frequency of the receptors is enhanced during increases in arterial pressure, resulting in an inhibition of vasoconstriction and peripheral vasodilation. Another systemic reflex is the BJR. The cardiac receptors mediating the BJR have very low basal firing rates in the absence of any stimulation, 13,27,28and output from these cardiac receptors contributes tonic inhibition to the vasomotor centers. 9,13,15,16,29–31These receptors, when stimulated by electrical excitation, show increased firing frequency with subsequent inhibition of the vasomotor centers, promoting vasodilation. 16,29 

Fig. 2. Anatomic configuration of the baroreceptor reflex (left ). Pressure receptors in the walls of the carotid sinuses and aorta detect arterial pressure changes in the circulation. These signals are conveyed to afferent receptive regions of the medulla via  Hering and the vagus nerves. Output from effector portions of the medulla modulates peripheral tone and heart rate. Increase in blood pressure results in increased activation of the reflex (right ), which effects a decrease in blood pressure.

Fig. 2. Anatomic configuration of the baroreceptor reflex (left ). Pressure receptors in the walls of the carotid sinuses and aorta detect arterial pressure changes in the circulation. These signals are conveyed to afferent receptive regions of the medulla via  Hering and the vagus nerves. Output from effector portions of the medulla modulates peripheral tone and heart rate. Increase in blood pressure results in increased activation of the reflex (right ), which effects a decrease in blood pressure.

It is well established that these BJR cardioinhibitory receptors, in conjunction with the aortic and carotid baroreceptors, participate in blood pressure regulation. There is an interaction between the two systems in blood pressure control such that they are complementary. 9,32Animal preparations, where the baroreceptors can be isolated from the systemic circulation, have proved useful in delineating this relationship. In normal intact animals, vagal cold block produces only mild increases in systemic blood pressure. In the experimental preparations, when the baroreceptors are active (i.e. , fully able to buffer blood pressure alterations), and cardioinhibitory receptor activity is lessened via  cold block of the vagus nerve, there is no or minimal vascular response (as with normal, intact animals;fig. 3). As baroreceptor activation is progressively withdrawn (i.e. , less able to modulate blood pressure changes), withdrawal of cardioinhibitory receptor activity produces increasing degrees of systemic hypertension, increased renal and mesenteric vascular resistance, decreased splanchnic capacitance, increased serum renin levels, and tachycardia. 29,32,33When free to exert buffering influence, the baroreceptor reflex can inhibit the blood pressure increase and renin release seen with vagal cold block (cardioinhibitory receptor withdrawal). 14Thus, when both systems are free to interact, the baroreceptor reflex appears to be the dominant regulator of blood pressure. That veratrum alkaloids can produce such a dramatic blood pressure response in the presence of an intact baroreceptor reflex (fig. 1) suggests that this relationship can be uncoupled, and the BJR activity can become dominant.

Fig. 3. Interaction between the baroreceptor and Bezold–Jarisch reflexes (BJRs) in blood pressure regulation. Decreased activity of the afferent limb of the BJR results in decreased firing of the afferent fibers of the BJR. This leads to a release of vasomotor inhibition with augmented medullary outflow and a consequent increase in blood pressure. However, with the baroreceptor reflex present, this increased blood pressure response is attenuated and the expected effect of withdrawal of BJR activity does not occur and there is no change in systemic blood pressure.

Fig. 3. Interaction between the baroreceptor and Bezold–Jarisch reflexes (BJRs) in blood pressure regulation. Decreased activity of the afferent limb of the BJR results in decreased firing of the afferent fibers of the BJR. This leads to a release of vasomotor inhibition with augmented medullary outflow and a consequent increase in blood pressure. However, with the baroreceptor reflex present, this increased blood pressure response is attenuated and the expected effect of withdrawal of BJR activity does not occur and there is no change in systemic blood pressure.


The cardioinhibitory receptors are also involved in the restorative response to systemic hypotension. As early as the 1970s, it had been shown that with comparable decreases in arterial pressure, there was more pronounced renal vasoconstriction with hemorrhagic versus  cardiogenic hypotension. 34–37This is somewhat surprising in that during hypotension, irrespective of cause, baroreflexes should trigger reflex systemic vasoconstriction and tachycardia to lessen the decrement in pressure. It is evident therefore that the actual physiologic response to hypotension is more complex than initially had been appreciated.

The sympathoinhibitory response of the BJR cardioinhibitory receptors is somewhat more active in the renal vascular system than in the vasculature of the limbs. 30In dogs, the renal vascular bed is under preferential control of these cardioinhibitory receptors, whereas the vascular beds of skeletal muscle are primarily under carotid baroreceptor control. 38–40Thus, the differential engagement of the carotid and BJR cardiac receptors with the central neuronal pool governing sympathetic outflow to the periphery dictates the relative role of each system in countering various stresses. 32,41–43This may explain why, in humans, renal vessels constrict with hypovolemic hypotension, whereas renal vessels dilate with cardiogenic hypotension.

Mild and Moderate Hypovolemia

The baroreceptor and cardioinhibitory receptor systems interact with one another during the maintenance of normal blood pressure, and this suggests that they also may have integrated responses to various degrees of hypovolemic insult. This interaction is shown by a series of experiments in dogs where mild hypovolemia was induced by bleeding (4 ml/kg). In animals with intact baroreceptors, there was no change in mean systolic, diastolic, and arterial pressures, but there was an increase in serum renin levels. 14,44,45These same studies also showed that the BJR cardiac vagal afferent fibers decrease their firing, thus partially releasing their tonic inhibition of vasomotor centers and increasing sympathetic traffic to the renal nerves. This occurs with no change in traffic from the carotid baroreceptors and without any clear activation of the sympathetic system as measured by change in heart rate or blood pressure. Thus cardioinhibitory receptors respond to decreases in blood volume to which baroreceptors are insensitive. The result of mild hypovolemic insult is a decrease in cardiac receptor activity (thereby augmenting vasomotor output). However, because the baroreceptor reflexes are intact , the expected response of tachycardia and increased vasomotor tone is blunted. During these conditions, the sole manifestation of decreased cardioinhibitory receptor activity is an increase in renin release. 14,44,45 

Despite this animal data 27,44and clinical data in healthy humans, which document unchanged heart rate and blood pressure during mild hemorrhage, 46–48the exact role that the cardioinhibitory receptor system plays in human hypovolemia is less clear. 41,42In humans with mild to moderate hemorrhage (400–650 ml) that decreases right atrial and pulmonary capillary wedge pressures (but not mean arterial pressures), there is no change or a slight decrease in renin release. 45With larger hemorrhage or with negative pressure (−40 mmHg) applied to the lower limbs, there were changes in heart rate and arterial blood pressure in conjunction with an increase in plasma renin levels. 49Therefore, it seems that a large enough hemorrhage can provoke increased renin release in humans and, in contrast to canine studies, this response is late and seen in conjunction with decreased mean arterial pressures and increased heart rates. 14,49The relative contributions of the baroreceptor and cardiac receptor systems to these changes have not been clarified.

Profound Hypovolemia

The literature is replete with reports documenting bradycardia during severe  (greater than 600 ml) hemorrhage in humans. 50–57The mechanism behind this response is unclear. There were attempts to link the BJR to the bradycardia observed during severe hemorrhage during the period between the 1930s and 1970s. Presumably, during mild and moderate hemorrhage in humans, the vasomotor inhibition exerted by cardioinhibitory afferent fibers and baroreceptor systems is released (as occurs in animals), resulting in an increase in blood pressure (fig. 4A). The issue is that during profound  hemorrhage, the expected hypotension can be accompanied by profound bradycardia. A paradoxical activation of the BJR could explain this occurrence. Specifically, the expected decreased activity of cardioinhibitory receptors (release of vasomotor inhibition) during profound hemorrhage does not occur and there is instead increased  receptor activity that further inhibits vasomotor output and triggers bradycardia (fig. 4B). There is some evidence for this notion in animals.

Fig. 4. Activation of the Bezold–Jarisch reflex (BJR) during hypovolemia. (A ) During conditions of moderate hypovolemia, the BJR and the baroreceptor reflex are synergistically active. The BJR activity is withdrawn simultaneously with activation of the baroreceptor reflex leading to an increase in blood pressure. (B ) During conditions of severe volume loss, not only is the BJR presumably paradoxically activated but the baroreceptor fails to exert its dominant blood pressure control effects either due to failed sensing at the afferent limb or inhibition of its efferent limb from some component of the BJR pathway. The net result is bradycardia and further hypotension.

Fig. 4. Activation of the Bezold–Jarisch reflex (BJR) during hypovolemia. (A ) During conditions of moderate hypovolemia, the BJR and the baroreceptor reflex are synergistically active. The BJR activity is withdrawn simultaneously with activation of the baroreceptor reflex leading to an increase in blood pressure. (B ) During conditions of severe volume loss, not only is the BJR presumably paradoxically activated but the baroreceptor fails to exert its dominant blood pressure control effects either due to failed sensing at the afferent limb or inhibition of its efferent limb from some component of the BJR pathway. The net result is bradycardia and further hypotension.

During severe hemorrhage in cats, increased firing of cardioinhibitory receptors has been recorded 58and a vigorous contraction of a relatively empty ventricle can trigger the cardiac vagal afferent fibers, which have been shown to lead to bradycardia, vasodilation, and hypotension. 59In humans, a sudden decrease in peripheral resistance coupled with decreased venous return triggers bradycardia presumably to preserve cardiac filling. 52These observations taken together suggest that the cardioinhibitory receptors may  become active during profound hypovolemia.

Myocardial Ischemia

Persons with myocardial ischemia and infarction display several autonomic disturbances, including arrhythmia, hypotension, and hypertension. 60A large number of people who suffer myocardial ischemia die from sudden cardiac death presumed secondary to cardiac arrhythmia. Bradyarrhythmias and hypotension are seen more commonly in patients with inferior or posterior wall myocardial ischemia and infarction, in contrast to anterior wall ischemia that often elicits tachyarrhythmias and hypotension. 60These discrete manifestations of hemodynamic responses to ischemia suggest different underlying mechanisms mediating them and a possible  role for BJR components. The distribution of the cardioinhibitory C fiber afferent receptors in the myocardium correlates well the coronary anatomy affected during myocardial ischemia 19,61–63with the concentration of cardiac inhibitory receptors greatest in the inferior and posterior walls of the heart, 23,63locations corresponding to the anatomic territory where myocardial ischemia is associated with hypotension and bradycardia. In addition, when veratridine is injected into the coronary circulation of dogs and cats, a greater degree of hypotension and bradycardia is seen during injections of the posterior/inferior circulation than with left anterior descending artery injections. 19The stimulus for reflex triggering during myocardial ischemia is not known, but there is some evidence for molecules generated during ischemia and reperfusion, such as oxygen-derived free radicals and prostaglandins. 64–66There is also evidence that the stimulus may be mechanical secondary to the aneurysmal bulging of myocardium that occurs during transmural ischemia. 18,20,67 

The purpose of this response during myocardial ischemia is unclear. As detailed previously, the same reflex has been implicated as a mechanism of sudden cardiac death during ischemic injury. 62At least one of the studies on humans details termination of electrocardiographic alterations consistent with ischemia by an episode of hypotension, bradycardia, and nausea. 68Those investigators have suggested that such a mechanism is protective. It also has been argued that the profound bradycardia and renal vasodilation reduces myocardial oxygen demand and augments renal perfusion that is beneficial in ischemia. 19,69 

Coronary Reperfusion

The concept that reperfusion of previously ischemic tissue is associated with unique morbidity has been recognized secondary to the advent of coronary reperfusion techniques utilizing intravenous lytic drugs and coronary angioplasty. 70Since the 1970s, it has been known that acute coronary occlusion and reperfusion in animal models could stimulate the cardioinhibitory receptors and potentially trigger the BJR, 18,20,65,67,71and this phenomenon is most pronounced with inferior or posterior reperfusion events. 63There also is evidence that the BJR may be involved in mediating the hypotension and bradycardia often seen during human coronary angiography with the injection of contrast media into the right coronary artery. 72 

Aortic Stenosis

The traditional teaching concerning exertional syncope in patients with aortic stenosis stresses the inability to increase cardiac output in the face of a fixed outflow obstruction. Of late, there has been a revival of an early twentieth century hypothesis that the cause of exertional syncope in aortic stenosis may be secondary to reflex activation of the BJR. 69,73–75The origin of this idea lies in observations that increases in left ventricular pressure could trigger cardioinhibitory reflexes and promote hypotension. 19,75It is argued that the cardiac vagal receptors, stimulated by vigorous contraction of the ventricle, triggers the BJR and may be responsible for this event. 69Exercise causes an increase in left ventricular pressure, which then triggers a cardiac reflex–mediated syncopal event. Further evidence for BJR involvement comes from observations made in the early 1970s in people with severe aortic stenosis. Normally, with exercise, the somatic pressor reflex causes peripheral vasoconstriction that serves to maintain mean arterial pressure and venous return in the face of augmented blood flow through the musculature. 26,76During skin blood flow testing of patients with severe aortic stenosis, a vasodilation, not vasoconstriction, in response to exercise was observed. Therefore, it was postulated that the initiating event for syncope in these patients may be a left ventricular–mediated reflex withdrawal of vasomotor tone in association with a loss of somatic pressor reflex.

Vasovagal Syncope

There is no clear consensus on either a mechanism or teleologic explanation as to the benefit of vasovagal syncope. Recall that during moderate systemic hemorrhage, decreased ventricular filling lessens the tonic activity of vagal afferent fibers causing increased sympathetic vasomotor activity resulting in “reflex” vasoconstriction and tachycardia. 27,45,49During severe hemorrhage, however, vigorous contraction of the empty ventricle may precipitate bradycardia and hypotension. 59The latter mechanism may account for the appearance of vasovagal syncope in the setting of orthostatic stresses. This is supported by the observation that treatment with β adrenergic blocking drugs has been shown to be effective in preventing some forms syncope. 77Many studies have attempted to tie such observations of bradycardia seen with hemorrhage to vasovagal mechanisms and therefore to the BJR. 3,4,8,53,78 

However, it remains unclear if this relationship truly exists. Cardiac transplant patients have had classic vasovagal syncope, even though there is no clear evidence for reinnervation of the transplanted heart. 79,80More recent experiments using echocardiography also fail to demonstrate either an empty ventricle or a more vigorous contraction as measured by end-systolic length or fractional systolic shortening during syncopal episodes. 81–83Therefore, vasovagal syncope is not synonymous with the BJR nor is it necessarily dependent upon cardioinhibitory receptor activation or the formal BJR.

Is the BJR Involved in Cardiovascular Collapse during Regional Anesthesia?

The Clinical Problem

There is accumulating evidence in the forms of case reports, closed claims analyses, and randomized trials that cardiovascular complications associated with regional anesthesia can include hypotension and bradycardia which can progress to complete cardiovascular collapse. These complications are not predictable and there exists neither a firm understanding of the cause of cardiac arrest nor any entirely effective interventions to counter such an event when it occurs. 84,85For these reasons this problem needs to be investigated more carefully.

Spinal and Epidural Anesthesia

The mechanisms of action, the pharmacology of the agents, and the clinical outcomes associated with regional anesthesia are all undergoing various forms of basic science and clinical investigation. A better understanding of many of the known side effects and risks associated with these techniques has evolved. The most common side effects from spinal and epidural anesthesia are cardiovascular. Hypotension and bradycardia are the most frequent with an incidence estimated to be 33 and 13% in nonobstetric populations, respectively. 86–88The incidence of cardiac arrest during spinal anesthesia has been estimated to range from 1/1600 to 1/250,000 89,90with a relatively greater incidence in younger, healthier males. 85Several case reports 6,7,86,89,91–100and closed claim analyses 101,102support the idea that severe circulatory complications are more frequent than had been appreciated. These reports share the common denominator that patients receiving spinal or epidural anesthesia were observed to have profound bradycardia with hypotension. This cardiovascular collapse was not anticipated, and in many cases, not treated effectively. 84,85,103Mortality from these events is low, but this does not negate the fact that these complications are severe and pose a significant threat to patients.

Etiology of the Bradycardia and Hypotension

The relative hypotension commonly associated with neuraxial blockade is secondary to sympathetic block. The block results in decreased systemic vascular resistance, peripheral vasodilation with redistribution of the central blood volume to the splanchnic circulation and lower extremities 104–106in conjunction with a possible slight decrease in myocardial contractility. 107,108The etiology of the bradycardia is less clear. There is some specific evidence from heart rate variability tracings 109as well as conjecture 84that there is a shift towards vagal predominance with neuraxial anesthesia. Supportive data are absent but it is conceivable that the cardioinhibitory receptors of the BJR may be responsible for the bradycardia. There is some evidence that cardiac afferent fiber activation may help to preserve diastolic filling time during relative decreases in venous return 52and that bradycardia is associated with echocardiographic evidence of smaller left ventricular chamber size. 110This mechanism implies that the bradycardia and hypotension in humans are not causally related to the true BJR but that the hypovolemic  (redistributive) hypotension invokes a protective  bradycardia mediated by cardioinhibitory afferent fibers. The BJR is a reflex that causes the triad of vasodilation, bradycardia and hypotension, and cardioinhibitory receptor-mediated bradycardia alone is not equivalent to the BJR. The appearance of bradycardia with hypotension may appear like BJR “mediated” syncope, but the bradycardia in these circumstances is actually the compensatory mechanism for some other  cause of peripheral vasodilation. This line of conjecture supports the conclusion that the bradycardia and hypotension observed during these clinical scenarios are manifestations of, at least , two separate processes. Whether the cardioinhibitory receptors actually  participate on any level has yet to be demonstrated.

Cardiac Arrests

Bradycardia also is a common feature of profound circulatory collapse under neuraxial anesthesia 50,51,53–57,111When explanations are offered in the literature, a wide variety of theoretical causes of cardiovascular collapse have been presented. These include activation of the baroreceptor reflex, 85,103sudden shifts in cardiac autonomic balance, 109activation of a reflex arc within myocardial pacemaker cells, 6the Bainbridge reflex, 84,112hypoxia and respiratory insufficiency, 101triggering of the cardioinhibitory receptors, and, ultimately, the BJR. 97,113When explanations of the BJR being responsible for the cardiovascular collapse are offered, they are presented as either a vasovagal mechanism that is stated as synonymous with the BJR, or as a “direct trigger” mechanism whereby the BJR is activated by some amalgam of factors present during regional anesthetic delivery. There are many possible explanations for these arrests, but with minimal supportive data in the literature, it is unclear whether the BJR or even the cardioinhibitory receptors have any role in their etiology.

Peripheral Nerve Blockade.

Reports of cardiovascular collapse are not limited to persons having neuraxial anesthesia. Patients undergoing peripheral nerve block techniques have been reported to have cardiovascular instability with dominant features of bradycardia and hypotension. In particular, shoulder procedures done during interscalene block with the patient in the sitting position appears to be the most common regional block technique associated with this presentation. 3,4,7,8It was hypothesized that the cause of the hypotension and bradycardia was based on a combination of peripheral vasodilation from the sitting position, increased contractility of the heart secondary to absorbed epinephrine from the injection of the block, and vigorous contraction of an empty ventricle. 3,4,6–8,78It is claimed that the three components resulted in activation of the BJR.

However, there are no convincing data in the literature to support these prerequisites. Oberg and Thorn 59hypothesized that vigorous mechanical contraction of an empty ventricle  is sufficient to trigger the afferent fibers in the wall of the ventricle and, therefore, the BJR. Some support for this empty ventricle concept during epidural  anesthesia is found in humans studies 114and by observations in humans made during tilt-table testing with venous pressure measurements, which showed a decreased ventricular volume. 115–117Other evidence obtained during lower extremity venous pooling 118or acute hemorrhage 47fail to demonstrate such changes and, in fact, reveal augmented cardiac output with increased chamber volume. Echocardiography data fail to demonstrate either an empty ventricle or more vigorous ventricular contraction during syncopal episodes. 81–83No evidence for venous pooling exists in the setting of peripheral  nerve blockade. The α adrenergic receptor agonist drugs such as phenylephrine can activate cardioinhibitory receptors, 119but there is no evidence of increased contractility in response to concentrations of epinephrine seen in local anesthetic mixtures for nerve block exists. 120In our institution, one patient experienced multiple episodes of hypotension and bradycardia associated with initiation of an infusion of 0.1% bupivacaine without  epinephrine via  a supraclavicular brachial plexus catheter during a two-day interval. In fact, one of the events occurred with the patient supine  (unpublished observations, February 1999, C. Carter M.D., Boston, Massachusetts, visual data). This case lends further doubt to the contention that the mechanism of cardiac arrest requires either augmentation of contractile function secondary to venous pooling induced orthostatically or by exogenous inotropism. In fact, taken as a whole, we believe that the literature support a mechanism other than the BJR  for the cause of the hypotension and bradycardia seen during shoulder surgery performed during interscalene block.


It is likely that Bezold–Jarisch cardioinhibitory receptors are involved in some manner in maintenance of normal blood pressure and in the response to hypovolemia. The same system may be active during myocardial infarction and coronary reperfusion. The BJR is not synonymous with vasovagal syncope, and there is no evidence that the cardioinhibitory receptors or the BJR per se  have a primary role in this type of syncope. Very little data exist that demonstrate cardioinhibitory receptor participation in the hemodynamic events observed during neuraxial anesthetics. The hemodynamic embarrassment seen in shoulder surgery during interscalene block appears not to be related to BJR activation.

An important issue to consider is to what extent is the BJR a physiologically dominant reflex? When triggered by Veratrum alkaloids, the subsequent hypotension and bradycardia suggest that the BJR is dominant under these conditions. That is, Veratrum alkaloids produce profound hypotension and bradycardia despite the presence and likely functioning of other homeostatic reflexes, such as the baroreceptor reflex. More “physiologic” stimuli, such as changes in blood pressure or intravascular volume, produce changes in pressure and heart rate that are balanced, integrated outcomes of multiple cardiovascular reflexes. Under these conditions, the BJR is not dominant, and profound cardiovascular collapse, as seen following the administration of Veratrum alkaloid, is not observed. No other documented effectors of the cardioinhibitory receptors have been shown to activate the BJR to the same dominant extent as Veratrum alkaloids. It follows that in order for the BJR to be a primary contributor to the cardiovascular collapse detailed in the anesthesia literature, whatever factors are present during the anesthetic techniques that stimulate the cardioinhibitory receptors, must do so to the same degree as veratrum alkaloids . These stimuli must allow the BJR to be dominant and be able to overcome the buffering power, or even negate other important homeostatic reflexes. Therefore, despite the appealing theoretic relation between hypotension, bradycardia, and cardiovascular collapse seen during neuraxial and regional anesthetic blockade (interscalene block) and the BJR, there is little evidence to support a role for the BJR in mediating these hemodynamic events. General acceptance that the BJR is responsible for these events should be discouraged until more data become available.

Further laboratory and clinical investigation are required before the clinical events documented in the anesthesia literature can be attributed to the BJR. Stimulators and inhibitors (effectors) of the cardioinhibitory receptors in humans need to be characterized and the full spectrum of the human efferent response to these factors should be investigated. These data need to be reconciled with the existing data from animal studies. Once this foundation is established, definitive demonstration of these effectors in clinical scenarios can be sought and evidence for the activation of the BJR can be determined. Informed clinical therapeutic recommendations cannot be forthcoming in the absence of such an understanding. The role of the BJR in human pathophysiology and anesthetic morbidity remains unclear.

The authors thank Jagmeet Singh, M.D., Ph.D. (Clinical Fellow in Cardiology, Department of Medicine) and Keith Baker, M.D., Ph.D. (Assistant Professor, Department of Anesthesia and Critical Care) from Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, for critical reading of the manuscript.


von Bezold AV, Hirt L: Uber die physiologischen wirkungen des essigsauren veratrins. Untersuchungen aus dem Physiologischen Laboratorium Wurzburg 1867; 1: 75–156
Dawes GS, Comroe JH: Chemoreflexes from the heart and lungs. Physiological Rev 1954; 34: 167–201
D'Alessio JG, Weller RS, Rosenblum M: Activation of the Bezold-Jarisch reflex in the sitting position for shoulder arthroscopy using interscalene block. Anesth Analg 1995; 80: 1158–62
Kahn RL, Hargett MJ: Beta-adrenergic blockers and vasovagal episodes during shoulder surgery in the sitting position under interscalene block. Anesth Analg 1999; 88: 378–81
Kinsella SM, Tuckey JP: Perioperative bradycardia and asystole: relationship to vasovagal syncope and the Bezold-Jarisch reflex. Br J Anaesth 2001; 86: 859–68
Liguori GA, Sharrock NE: Asystole and severe bradycardia during epidural anesthesia in orthopedic patients. A nesthesiology 1997; 86: 250–7
Liguori GA, Kahn RL, Gordon J, Gordon MA, Urban MK: The use of metoprolol and glycopyrrolate to prevent hypotensive/bradycardic events during shoulder arthroscopy in the sitting position under interscalene block. Anesth Analg 1998; 87: 1320–5
Morris GN: The Bezold-Jarisch reflex. Anesth Analg 1996; 83: 201–2
Donald DE, Shepard JT: Reflexes from the heart and lungs: physiological curiosities or important regulatory mechanisms. Cardiovasc Res 1978; 12: 449–69
Jarisch A, Richter H: Die afferenten bahnen des veratrine effektes in den herznerven. Arch Exp Pathol Pharmacol 1939; 193: 355–71
Jarisch A, Richter H: Die kreislauf des veratrins. Arch Exp Pathol Pharmacol 1939; 193: 347–54
Dawes GS, Mott JC, Widdicombe JG: The depressor actions of the veratrum alkaloids. Br J Pharmacol 1951; 6: 675–81
Oberg B, Thoren P: Studies on left ventricular receptors, signalling in non-medullated vagal afferents. Acta Physiol Scand 1972; 85: 145–63
Thames MD, Jarecki M, Donald DE: Neural control of renin secretion in anesthetized dogs. Interaction of cardiopulmonary and carotid baroreceptors. Circ Res 1978; 42: 237–45
Thoren PN, Mancia G, Shepherd JT: Vasomotor inhibition in rabbits by vagal nonmedullated fibers from cardiopulmonary area. Am J Physiol 1975; 229: 1410–3
Oberg B, Thoren P: Circulatory responses to stimulation of medullated and non-medullated afferents in the cardiac nerve in the cat. Acta Physiol Scand 1973; 87: 121–32
Aviado DM, Guevara Aviado D: The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes. Ann N Y Acad Sci 2001; 940: 48–58
Thoren PN: Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat. Am J Cardiol 1976; 37: 1046–51
Mark AL: The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. J Am Coll Cardiol 1983; 1: 90–102
Thoren P: Left ventricular receptors activated by severe asphyxia and by coronary artery occlusion. Acta Physiol Scand 1972; 85: 455–63
Thoren PN: Characteristics of left ventricular receptors with nonmedullated vagal afferents in cats. Circ Res 1977; 40: 415–21
Thames MD, Donald DE, Shepherd JT: Behavior of cardiac receptors with nonmyelinated vagal afferents during spontaneous respiration in cats. Circ Res 1977; 41: 694–701
Dawes GS: Reflexes from the heart and lungs. Brish Medical Bulletin 1950; 4: 324–30
Dawes GS: Studies on the veratrum alkaloids: VII. Receptor areas in the coronary arteries and elsewhere as revealed by the use of veratridine. 1946: 325–42
Krayer O, Acheson GH: The pharmacology of the veratrum alkaloids. J Pharmacol and Exper Therap 1946; 86: 383–446
Guyton AC, Coleman TG, Fourcade JC, Navar LG: Physiologic control of arterial pressure. Bull N Y Acad Med 1969; 45: 811–30
Oberg B, White S: The role of vagal cardiac nerves and arterial baroreceptors in the circulatory adjustments to hemorrhage in the cat. Acta Physiol Scand 1970; 80: 395–403
Oberg B, White S: Circulatory effects of interruption and stimulation of cardiac vagal afferents. Acta Physiol Scand 1970; 80: 383–94
Oberg B, Thoren P: Circulatory responses to stimulation of left ventricular receptors in the cat. Acta Physiol Scand 1973; 88: 8–22
Mancia G, Romero JC, Shepherd JT: Continuous inhibition of renin release in dogs by vagally innervated receptors in the cardiopulmonary region. Circ Res 1975; 36: 529–35
Mancia G, Donald DE, Shepherd JT: Inhibition of adrenergic outflow to peripheral blood vessels by vagal afferents from the cardiopulmonary region in the dog. Circ Res 1973; 33: 713–21
Mancia G, Shepherd JT, Donald DE: Interplay among carotid sinus, cardiopulmonary, and carotid body reflexes in dogs. Am J Physiol 1976; 230: 19–24
Thames MD: Reflex suppression of renin release by ventricular receptors with vagal afferents. Am J Physiol 1977; 233: H181–4
Ustinova EE, Schultz HD: Renal sympathetic nerve activity during cardiac ischemia and reperfusion in rats. Am J Physiol 1996; 271: R1033–40
Hanley HG, Raizner AE, Inglesby TV, Skinner NS Jr: Response of the renal vascular bed to acute experimental coronary arterial occlusion. Am J Cardiol 1972; 29: 803–8
Gorfinkel HJ, Szidon JP, Hirsch LJ, Fishman AP: Renal performance in experimental cardiogenic shock. Am J Physiol 1972; 222: 1260–8
Thames MD, Abboud FM: Reflex inhibition of renal sympathetic nerve activity during myocardial ischemia mediated by left ventricular receptors with vagal afferents in dogs. J Clin Invest 1979; 63: 395–402
Roddie IC: Nervous control of limb blood flow. Sci Basis Med Annu Rev 1966; 260–78
Bevegard BS, Shepherd JT: Reaction in man of resistance and capacity vessels in forearm and hand to leg exercise. J Appl Physiol 1966; 21: 123–32
Bevegard BS, Shepherd JT: Circulatory effects of stimulating the carotid arterial stretch receptors in man at rest and during exercise. J Clin Invest 1966; 45: 132–42
Mancia G, Ferrari A, Gregorini L, Valentini R, Ludbrook J, Zanchetti A: Circulatory reflexes from carotid and extracarotid baroreceptor areas in man. Circ Res 1977; 41: 309–15
Abboud FM, Mark AL, Thames MD: Modulation of the somatic reflex by carotid baroreceptors and by cardiopulmonary afferents in animals and in humans. Circ Res 1981; 48: I131–7
Lee TM, Kuo JS, Chai CY: Central integrating mechanism of the Bezold-Jarisch and baroceptor reflexes. Am J Physiol 1972; 222: 713–20
Jarecki M, Thoren PN, Donald DE: Release of renin by the carotid baroreflex in anesthetized dogs. Role of cardiopulmonary vagal afferents and renal arterial pressure. Circ Res 1978; 42: 614–9
Gupta PD, Henry JP, Sinclair R, Von Baumgarten R: Responses of atrial and aortic baroreceptors to nonhypotensive hemorrhage and to tranfusion. Am J Physiol 1966; 211: 1429–37
Price HL, Deutsch S, Marshall BE, Stephen GW, Behar MG, Neufeld GR: Hemodynamic and metabolic effects of hemorrhage in man, with particular reference to the splanchnic circulation. Circ Res 1966; 18: 469–74
Skillman JJ, Olson JE, Lyons JH, Moore FD: The hemodynamic effect of acute blood loss in normal man, with observations on the effect of the Valsalva maneuver and breath holding. Ann Surg 1967; 166: 713–38
Skillman JJ, Lauler DP, Hickler RB, Lyons JH, Olson JE, Ball MR, Moore FD: Hemorrhage in normal man: effect on renin, cortisol, aldosterone, and urine composition. Ann Surg 1967; 166: 865–85
Brown JJ, Davies DL, Lever AF, Robertson JI, Verniory A: The effect of acute haemorrhage in the dog and man on plasma-renin concentration. J Physiol 1966; 182: 649–63
Grant RT, Reeve EB: Clinical observation on air raid casualties. BMJ 1941; 2: 329–332
McMichael J: Clinical aspects of shock. JAMA 1944; 124: 275–81
Sander-Jensen K, Marving J, Secher NH, Hansen IL, Giese J, Warberg J, Bie P: Does the decrease in heart rate prevent a detrimental decrease of the end-systolic volume during central hypovolemia in man? Angiology 1990; 41: 687–95
Sander-Jensen K, Secher NH, Bie P, Warberg J, Schwartz TW: Vagal slowing of the heart during haemorrhage: observations from 20 consecutive hypotensive patients. BMJ (Clin Res Ed) 1986; 292: 364–6
Secher NH, Bie P: Bradycardia during reversible haemorrhagic shock–a forgotten observation? Clin Physiol 1985; 5: 315–23
Secher NH, Sander Jensen K, Werner C, Warberg J, Bie P: Bradycardia during severe but reversible hypovolemic shock in man. Circ Shock 1984; 14: 267–74
Jacobsen J, Secher NH: Heart rate during haemorrhagic shock. Clin Physiol 1992; 12: 659–66
Secher NH, Jacobsen J, Friedman DB, Matzen S: Bradycardia during reversible hypovolaemic shock: associated neural reflex mechanisms and clinical implications. Clin Exp Pharmacol Physiol 1992; 19: 733–43
Oberg B, Thoren P: Increased activity in vagal cardiac afferents correlated to the appearance of reflex bradycardia during severe hemorrhage in cats. Acta Physiol Scand 1970; 80: 22–23A
Oberg B, Thoren P: Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat. A possible cause of the vaso-vagal reaction. Acta Physiol Scand 1972; 85: 164–73
Webb SW, Adgey AA, Pantridge JF: Autonomic disturbance at onset of acute myocardial infarction. BMJ 1972; 3: 89–92
Recordati G, Schwartz PJ, Pagani M, Malliani A, Brown AM: Activation of cardiac vagal receptors during myocardial ischemia. Experientia 1971; 27: 1423–4
Robertson D, Hollister AS, Forman MB, Robertson RM: Reflexes unique to myocardial ischemia and infarction. J Am Coll Cardiol 1985; 5: 99–104B
Thames MD, Klopfenstein HS, Abboud FM, Mark AL, Walker JL: Preferential distribution of inhibitory cardiac receptors with vagal afferents to the inferoposterior wall of the left ventricle activated during coronary occlusion in the dog. Circ Res 1978; 43: 512–9
Schultz HD, Ustinova EE: Cardiac vagal afferent stimulation by free radicals during ischaemia and reperfusion. Clin Exp Pharmacol Physiol 1996; 23: 700–8
Ustinova EE, Schultz HD: Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals. Circ Res 1994; 74: 904–11
Ustinova EE, Schultz HD: Activation of cardiac vagal afferents by oxygen-derived free radicals in rats. Circ Res 1994; 74: 895–903
Thoren P: Evidence for a depressor reflex elicited from left ventricular receptors during occlusion of one coronary artery in the cat. Acta Physiol Scand 1973; 88: 23–34
Robertson RM, Robertson D: The Bezold-Jarisch reflex: possible role in limiting myocardial ischemia. Clin Cardiol 1981; 4: 75–9
Longhurst JC: Cardiac receptors: their function in health and disease. Prog Cardiovasc Dis 1984; 27: 201–22
Yamada M, Hearse DJ, Curtis MJ: Reperfusion and readmission of oxygen. Pathophysiological relevance of oxygen-derived free radicals to arrhythmogenesis. Circ Res 1990; 67: 1211–24
Koren G, Weiss AT, Ben-David Y, Hasin Y, Luria MH, Gotsman MS: Bradycardia and hypotension following reperfusion with streptokinase (Bezold-Jarisch reflex): a sign of coronary thrombolysis and myocardial salvage. Am Heart J 1986; 112: 468–71
Arrowood JA, Mohanty PK, Hodgson JM, Dibner-Dunlap ME, Thames MD: Ventricular sensory endings mediate reflex bradycardia during coronary arteriography in humans. Circulation 1989; 80: 1293–300
Johnson AM: Aortic stenosis, sudden death, and the left ventricular baroceptors. Br Heart J 1971; 33: 1–5
Mark AL, Kioschos JM, Abboud FM, Heistad DD, Schmid PG: Abnormal vascular responses to exercise in patients with aortic stenosis. J Clin Invest 1973; 52: 1138–46
Mark AL, Abboud FM, Schmid PG, Heistad DD: Reflex vascular responses to left ventricular outflow obstruction and activation of ventricular baroreceptors in dogs. J Clin Invest 1973; 52: 1147–53
Cowley AR, Guyton AC: Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res 1973; 32: 564–76
Dickinson CJ: Fainting precipitated by collapse-firing of venous baroreceptors. Lancet 1993; 342: 970–2
Stienstra R: Mechanisms behind and treatment of sudden, unexpected circulatory collapse during central neuraxis blockade. Acta Anaesthesiol Scand 2000; 44: 965–71
Montebugnoli L, Montanari G: Vasovagal syncope in heart transplant patients during dental surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 87: 666–9
Scherrer U, Vissing S, Morgan BJ, Hanson P, Victor RG: Vasovagal syncope after infusion of a vasodilator in a heart-transplant recipient. N Engl J Med 1990; 322: 602–4
Davrath LR, Gotshall RW, Tucker A, Sadeh WZ, Luckasen GJ, Downes TR, Coonts CC: The heart is not necessarily empty at syncope. Aviat Space Environ Med 1999; 70: 213–9
Liu JE, Hahn RT, Stein KM, Markowitz SM, Okin PM, Devereux RB, Lerman BB: Left ventricular geometry and function preceding neurally mediated syncope. Circulation 2000; 101: 777–83
Novak V, Honos G, Schondorf R: Is the heart “empty’ at syncope? J Auton Nerv Syst 1996; 60: 83–92
Pollard JB: Cardiac arrest during spinal anesthesia: common mechanisms and strategies for prevention. Anesth Analg 2001; 92: 252–6
Pollard JB: Common mechanisms and strategies for prevention and treatment of cardiac arrest during epidural anesthesia. J Clin Anesth 2002; 14: 52–6
Sprung J, Abdelmalak B, Schoenwald PK: Vasovagal cardiac arrest during the insertion of an epidural catheter and before the administration of epidural medication. Anesth Analg 1998; 86: 1263–5
Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R: Incidence and risk factors for side effects of spinal anesthesia. A nesthesiology 1992; 76: 906–16
Palmer SK: What is the incidence of arrest and near arrest during spinal and epidural analgesia? Report of nine years’ experience in an academic group practice. Anesth Analg 2001; 92: S339
Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K: Serious complications related to regional anesthesia: results of a prospective survey in France. A nesthesiology 1997; 87: 479–86
Go AS, Browner WS: Cardiac outcomes after regional or general anesthesia. Do we have the answer? Anesthesiology 1996; 84: 1–2
Chan KK, Welch KJ: Cardiac arrest during segmental thoracic epidural anesthesia. A nesthesiology 1997; 86: 503–5
Dobson PM, Caldicott LD, Gerrish SP: Delayed asystole during spinal anaesthesia for transurethral resection of the prostate. Eur J Anaesthesiol 1993; 10: 41–3
Geffin B, Shapiro L: Sinus bradycardia and asystole during spinal and epidural anesthesia: a report of 13 cases. J Clin Anesth 1998; 10: 278–85
Gibbons JJ, F.F. D: Sudden asystole after spinal anesthesia treated with the “pacing thump”. A nesthesiology 1991; 75: 705–706
Gild W, Crilley P: Sudden cardiac arrest during epidural anesthesia. A nesthesiology 1990; 73: 1296–1297
Jordi EM, Marsch SC, Strebel S: Third degree heart block and asystole associated with spinal anesthesia. A nesthesiology 1998; 89: 257–60
Lovstad RZ, Granhus G, Hetland S: Bradycardia and asystolic cardiac arrest during spinal anaesthesia: a report of five cases. Acta Anaesthesiol Scand 2000; 44: 48–52
Mackey DC, Carpenter RL, Thompson GE, Brown DL, Bodily MN: Bradycardia and asystole during spinal anesthesia: a report of three cases without morbidity. A nesthesiology 1989; 70: 866–8
Nishikawa T, Anzai Y, Namiki A: Asystole during spinal anaesthesia after change from Trendelenburg to horizontal position. Can J Anaesth 1988; 35: 406–8
Tarkkila PJ, Kaukinen S: Complications during spinal anesthesia: a prospective study. Reg Anesth 1991; 16: 101–6
Caplan RA, Ward RJ, Posner K, Cheney FW: Unexpected cardiac arrest during spinal anesthesia: a closed claims analysis of predisposing factors. A nesthesiology 1988; 68: 5–11
Aromaa U, Lahdensuu M, Cozanitis DA: Severe complications associated with epidural and spinal anaesthesias in Finland 1987–1993. A study based on patient insurance claims. Acta Anaesthesiol Scand 1997; 41: 445–52
Gratadour P, Viale JP, Parlow J, Sagnard P, Counioux H, Bagou G, Annat G, Hughson R, Quintin L: Sympathovagal effects of spinal anesthesia assessed by the spontaneous cardiac baroreflex. A nesthesiology 1997; 87: 1359–67
Sancetta SM, Lynn RB, Simeone FA, Scott RW: Studies of hemodynamic changes in Humans following induction of low and high spinal anesthesia. Circ Res 1952; 6: 559–71
Critchley LA, Conway F: Hypotension during subarachnoid anaesthesia: haemodynamic effects of colloid and metaraminol. Br J Anaesth 1996; 76: 734–6
Rooke GA, Freund PR, Jacobson AF: Hemodynamic response and change in organ blood volume during spinal anesthesia in elderly men with cardiac disease. Anesth Analg 1997; 85: 99–105
Blomberg S, Emanuelsson H, Ricksten SE: Thoracic epidural anesthesia and central hemodynamics in patients with unstable angina pectoris. Anesth Analg 1989; 69: 558–62
Saada M, Catoire P, Bonnet F, Delaunay L, Gormezano G, Macquin-Mavier I, Brun P: Effect of thoracic epidural anesthesia combined with general anesthesia on segmental wall motion assessed by transesophageal echocardiography. Anesth Analg 1992; 75: 329–35
Critchley LA, Chan S, Tam YH: Spectral analysis of sudden bradycardia during intrathecal meperidine anesthesia. Reg Anesth Pain Med 1998; 23: 506–10
Jacobsen J, Sofelt S, Brocks V, Fernandes A, Warberg J, Secher NH: Reduced left ventricular diameters at onset of bradycardia during epidural anaesthesia. Acta Anaesthesiol Scand 1992; 36: 831–6
Jacobsen J, Secher NH: Slowing of the heart during anaphylactic shock. A report of five cases. Acta Anaesthesiol Scand 1988; 32: 401–3
Thrush DN, Downs JB: Vagotonia and cardiac arrest during spinal anesthesia. A nesthesiology 1999; 91: 1171–3
Liu SS, McDonald SB: Current issues in spinal anesthesia. A nesthesiology 2001; 94: 888–906
Baron JF, Decaux-Jacolot A, Edouard A, Berdeaux A, Samii K: Influence of venous return on baroreflex control of heart rate during lumbar epidural anesthesia in humans. A nesthesiology 1986; 64: 188–93
Nwosu EA, Rahko PS, Hanson P, Grogan EW Jr: Hemodynamic and volumetric response of the normal left ventricle to upright tilt testing. Am Heart J 1994; 128: 106–13
Shalev Y, Gal R, Tchou PJ, Anderson AJ, Avitall B, Akhtar M, Jazayeri MR: Echocardiographic demonstration of decreased left ventricular dimensions and vigorous myocardial contraction during syncope induced by head-up tilt. J Am Coll Cardiol 1991; 18: 746–51
Yamanouchi Y, Jaalouk S, Shehadeh AA, Jaeger F, Goren H, Fouad-Tarazi FM: Changes in left ventricular volume during head-up tilt in patients with vasovagal syncope: an echocardiographic study. Am Heart J 1996; 131: 73–80
Warren JV, Grannon ES, Stead EA, Merrill AJ: The effect of venesection and the pooling of blood in the extermities on the atrial pressure and cardiac output in normal subjects with observations on acute circulatory collapse in three instances. J Clin Invest 1945; 24: 337–344
Minisi AJ, Dibner-Dunlap M, Thames MD: Vagal cardiopulmonary baroreflex activation during phenylephrine infusion. Am J Physiol 1989; 257: R1147–53
Bonica JJ, Akamatsu TJ, Berges PU, Morikawa K, Kennedy WF Jr: Circulatory effects of peridural block. II. Effects of epinephrine. A nesthesiology 1971; 34: 514–22 The Bezold–Jarisch Reflex is a cardiac reflex with limited, but clear importance in human physiology. There is, however, little evidence in the literature to support its role in the etiology of cardiac arrest seen during regional anesthetic techniques.