Elsevier

Heart Rhythm

Volume 13, Issue 3, March 2016, Pages 798-805
Heart Rhythm

Contemporary Review
Cardiac output and vasodilation in the vasovagal response: An analysis of the classic papers

https://doi.org/10.1016/j.hrthm.2015.11.023Get rights and content

The simple faint is secondary to hypotension and bradycardia resulting in transient loss of consciousness. According to Ohm’s law applied to the circulation, BP = SVR × CO, hypotension can result from a decrease in systemic vascular resistance (SVR), cardiac output (CO), or both. It is important to understand that when blood pressure (BP) is falling, SVR and CO do not change reciprocally as they do in the steady state. In 1932, Lewis, assuming that decreased SVR alone accounted for hypotension, defined “the vasovagal response” along pathophysiologic lines to denote the association of vasodilation with vagal-induced bradycardia in simple faint. Studies performed by Barcroft and Sharpey-Schafer between 1940 and 1950 used volume-based plethysmography to demonstrate major forearm vasodilation during extreme hypotension and concluded that the main mechanism for hypotension was vasodilation. Plethysmographic measurements were intermittent and not frequent enough to capture rapid changes in blood flow during progressive hypotension. However, later investigations by Weissler, Murray, and Stevens performed between 1950 and 1970 used invasive beat-to-beat BP measurements and more frequent measurements of CO using the Fick principle. They demonstrated that CO significantly fell before syncope, and little vasodilation occurred until very late in the vasovagal reaction Thus, since the 1970s, decreasing cardiac output rather than vasodilation has been regarded as the principal mechanism for the hypotension of vasovagal syncope.

Introduction

Syncope is defined as a transient loss of consciousness secondary to global cerebral hypoperfusion and is characterized by rapid onset, short duration, and spontaneous complete recovery.1 During vasovagal syncope (or fainting), the fall in blood pressure (BP) is mediated initially by decreased cardiac output (CO) with or without vasodilation. The decrease in CO is secondary to stroke volume reduction. When bradycardia and withdrawal of sympathetic vasoconstrictor activity occur, they are relatively late events, by which time BP is already low. There has been much debate as to whether decreased CO or vasodilation is the dominant hypotensive mechanism preceding vasovagal syncope.2, 3

Tilt testing was first used by Weiss et al4 for investigating orthostasis and by Graybiel and McFarland5 as a means of studying tolerance to decreased venous return as a determinant of fitness for military aviation. In 1986, Kenny, Sutton, and coworkers6 introduced tilt testing as a means of diagnosing vasovagal syncope. Since then, cardiologists, physicians, and researchers have adopted this approach to evaluate the hemodynamics of vasovagal syncope and other conditions related to orthostatic intolerance.1 In the 1980s, Penaz and Wesseling introduced the Finapres or volume clamp method, which allowed continuous noninvasive measurement of finger arterial pressure. Thus, rapid changes in arterial pressure could be obtained accurately. Pulse wave analysis subsequently allowed the computation of relative changes in stroke volume (SV) and thereby calculated relative changes in CO and systemic vascular resistance (SVR). These scientific developments enabled clinicians and researchers to study noninvasively the vasovagal responses on a beat-to-beat basis.7, 8 In addition, direct nerve recordings from the leg using the microneurographic technique enabled continuous monitoring of efferent vasoconstrictor sympathetic activity. Observations obtained from relatively small numbers of cases have demonstrated changes in sympathetic vasoconstrictor tone during vasovagal syncope, but this is only activity directed toward the leg.3

Despite these developments, the mechanisms underlying vasovagal syncope are still being debated.2, 3 Most arguments rely on the classic experiments performed before the 1980s. These results emphasized that vasodilation is the dominant mechanism initiating the vasovagal response

We performed an in-depth critical overview of the classic literature related to the mechanisms underlying vasovagal syncope to provide a comprehensive historical summary.

Section snippets

Methods

Referenced papers were selected by hand searches of our own databases. For focused searches, PubMed was used as the preferred database. All available studies were checked for relevance to the present review. For the mechanisms involved in orthostatic BP control in healthy subjects, we refer to standard texts.2, 9

Historic overview

During World War I, Cotton and Lewis10 studied recruits with “the irritable heart” or “the effort syndrome,” in whom fainting was frequent. Findings from 8 soldiers (age 21–28 years) who fainted during medical examinations were presented with vivid descriptive precision and with great care. Heart rate (HR) was measured by counting the radial pulse or auscultation of the heart, and BP was determined using an arm cuff and stethoscope.

In 6 soldiers, the faint was elicited during blood sampling

Summary

  • 1.

    Fewer than 10 young adult healthy males without a fainting history were studied in early laboratory studies (Table 1). Females, seniors, and patients were not studied. In addition, subjects were instrumented, which greatly influences fainting responses. Thus, the classic studies included only a selected healthy male population under highly invasive conditions.

  • 2.

    The circulatory changes during a faint are rapid, and the time between onset of hypotension and loss of consciousness is crucial.

Acknowledgments

We gratefully acknowledge the critical comments of Jacques Lenders, Paul Fadel, Roland Thijs, and Mike Joyner.

References (35)

  • B.P.M. Imholz et al.

    Fifteen-years-experience with finger arterial pressure monitoring: assessment of the technology

    Cardiovasc Res

    (1998)
  • B.E. Westerhof et al.

    Bridging cardiovascular physics, physiology, and clinical practice: Karel Wesseling, pioneer of continuous noninvasive hemodynamic monitoring

    Am J Physiol Heart Circ Physiol

    (2015)
  • W. Wieling et al.

    Maintenance of postural normotension in humans

  • T.F. Cotton et al.

    Observations upon fainting attacks due to inhibitory cardiac impulses

    Heart

    (1918–1920)
  • T. Lewis

    Vasovagal syncope and the carotid sinus mechanism

    Br Med J

    (1932)
  • W.R. Gowers

    Border-Land of Epilepsy, Faints, Vagal Attacks, Vertigo, Migraine

    Sleep Symptoms and Their Treatment

    (1907)
  • H. Barcroft et al.

    On the vasodilatation in human skeletal muscle during post-haemorrhagic fainting

    J Physiol

    (1945)
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