Blood pressure regulation X: what happens when the muscle pump is lost? Post-exercise hypotension and syncope

Abstract

Syncope which occurs suddenly in the setting of recovery from exercise, known as post-exercise syncope, represents a failure of integrative physiology during recovery from exercise. We estimate that between 50 and 80% of healthy individuals will develop pre-syncopal signs and symptoms if subjected to a 15-min head-up tilt following exercise. Post-exercise syncope is most often neurally mediated syncope during recovery from exercise, with a combination of factors associated with post-exercise hypotension and loss of the muscle pump contributing to the onset of the event. One can consider the initiating reduction in blood pressure as the tip of the proverbial iceberg. What is needed is a clear model of what lies under the surface; a model that puts the observational variations in context and provides a rational framework for developing strategic physical or pharmacological countermeasures to ultimately protect cerebral perfusion and avert loss of consciousness. This review summarizes the current mechanistic understanding of post-exercise syncope and attempts to categorize the variation of the physiological processes that arise in multiple exercise settings. Newer investigations into the basic integrative physiology of recovery from exercise provide insight into the mechanisms and potential interventions that could be developed as countermeasures against post-exercise syncope. While physical counter maneuvers designed to engage the muscle pump and augment venous return are often found to be beneficial in preventing a significant drop in blood pressure after exercise, countermeasures that target the respiratory pump and pharmacological countermeasures based on the involvement of histamine receptors show promise.

FIGURE 1

Early observations of the muscle pump. Panel A: Changes in calf volume with muscle contraction as measured by plethysmography. E denotes the onset of exercise (plantar flexion at 1 Hz for 10 s); R denotes onset of rest; CP denotes inflation of a cuff above the knee to 90 mmHg for remainder of tracing. This early study shows the considerable volume of blood that can be mobilized from the calf in response to modest muscle contractions, as well as showing that the muscle pump is capable of moving blood against a considerable pressure gradient. (Reproduced from Barcroft & Dornhorst, 1949). Panel B: Changes in saphenous vein pressure with walking on a treadmill at 1.7 mph. Step-by-step changes in minimum and maximum vein pressure at the level of the ankle during quiet standing (control), slow walking, and quiet standing after walking. This early study shows that dependent limb venous pressure can be markedly reduced within a few steps by engagement of the muscle pump, as well as the rate at which venous pressure will return that that predicted by gravitational forces when muscle pump activity ceases. (Reproduced from Pollack & Wood, 1949).

FIGURE 2. Integrated hemodynamic responses following exercise

Regulated reductions in blood pressure known as post-exercise hypotension can be large enough in magnitude to induce pre-syncopal symptoms and lead to post-exercise syncope. The expression of post-exercise hypotension is the integration of a variety of obligatory and situational components. Obligatory components (indicated in pale blue) include 1) a sustained histaminergic vasodilation of the previously exercise skeletal muscle vascular beds, 2) resetting of the baroreflex (which generally results in sympathoinhibition of sympathetic nerves to muscle vascular beds), 3) pre-synaptic inhibition of norepinephrine release from sympathetic nerves to the exercised muscle, and 4) resetting of thermoreflexes. These changes manifest as a rise in vascular conductance of the previously exercised muscle, inhibition of sympathetic vasoconstrictor nerve activity to previously active muscle vascular beds, and little or no change in cutaneous vascular conductance despite higher core temperatures. Situational components (indicated in light yellow) include the impact of whether or not significant fluid loss, gravitational pooling of blood, and hyperthermia are present. These components can greatly impact on the extent to which cardiac output is elevated. (Reproduced from Halliwill et al., 2013).

FIGURE 3. Sex and age of patients evaluated with post-exercise syncope

Panel A: The percentage of male and female patients in case reports. Panel B: The distribution of case reports on post-exercise syncope by age. Both figures are based on data from references listed in Table 1 (n = 27).

FIGURE 4. Survival time during head-up tilt following exercise - two models and two countermeasures

The proportion of subjects remaining in the tilted position as shown by survival function curve. Panel A: Effect of H₁-receptor blockade on head-up tilt after 45 min running in the heat. (Modified from McCord et al., 2008). Panel B: Effect of inspiratory resistance on head-up tile after 1 min high-intensity exercise. (Modified from Lacewell et al., 2013). Solid line represents the control day; dotted line, countermeasure day.