Causes of syncope

Such reductions in blood pressure could result from reduced venous return and cardiac filling or from reduced baroreflex capacity to induce peripheral vasoconstriction. In the context of exercise, the typical primary effect is obstructed systemic venous return due to elevation of intrathoracic pressure. This pressure increase can be induced voluntarily by forced expiration against a closed glottis and is known as the Valsalva manoeuvre (Fig. 10.1). It occurs naturally during any activity that involves thoracic muscle activation and breath holding, such as carrying heavy suitcases, weight lifting or straining on the lavatory.

Figure 10.1 Effects on blood pressurfilling or from reduced baroreflex capacity to induce peripherale and heart rate of 10 s forced expiration against a resistance of 44 mHg, in a young, healthy adult. During the Valsalva manoeuvre, reduced venous return is compensated by increased sympathetic vasoconstriction and tachycardia, which together restore mean blood pressure near to the pre-test value. The fact that this restoration is not complete until near the end of the manoeuvre reflects the slow time course of vascular smooth muscle contraction following sympathetic activation. This is mirrored by the relative bradycardia that occurs over the 10 s after cessation of the manoeuvre and reflects the bradycardic baroreflex response to elevated peripheral resistance.

In normal, healthy individuals, the arterial baroreflex responses to reduced stroke volume (increased peripheral resistance and tachycardia) are usually fast and large enough to maintain blood pressure at a level that allows adequate cerebral perfusion. Several factors can, however, reduce the effectiveness of these compensations so that consciousness is impaired. Reduced blood volume will reduce the efficiency of cardiac filling and so exaggerate the fall in stroke volume. Increased venous compliance will lead to greater pooling of blood in dependent veins, with less efficient mobilization of this for any given degree of sympathetic vasoconstrictor activation. Finally, any blood-borne influences that cause cerebral vasoconstriction will reduce cerebral perfusion further at any given blood pressure.

All of these additional factors may be associated with athletic performance of specific types. In competitions that involve weight divisions, many performers restrict their fluid intake dramatically in order to make weight, with resulting depletion of plasma volume. Intense, long-term dynamic training has been reported to cause increases in compliance of the large veins, predisposing these athletes to increased venous pooling and to hypotension and fainting during rapid postural change, even in the absence of a Valsalva manoeuvre (Hernandez & Franke 2004). Finally, the elevation of plasma adrenaline (epinephrine) and noradrenaline (norepinephrine) due to the generalized sympathetic discharge associated with central command is enhanced by the additional sympathetic activation due to the stress of competition. Although the cerebral vasculature itself receives only a sparse sympathetic innervation, these circulating catecholamines exert a moderate vasoconstrictor effect on the cerebral precapillary resistance vessels and so reduce brain perfusion at any given level of pressure gradient. An example of Valsalva-induced syncope in a competitive athlete appears in the Case history below.

Comment

Weight lifting, along with many other forms of static and resistive exercises involving the upper body, necessarily causes a very substantial increase in intrathoracic pressure. This is equivalent to a Valsalva manoeuvre and consequently reduces venous return, stroke volume and blood pressure.

In Joe’s case, several interactive factors were probably involved in the Valsalva manoeuvre during competition producing such a severe fall in blood pressure that he lost consciousness. First, his restricted fluid intake prior to competition would have lowered his plasma volume and reduced the amount of blood that could be mobilized from his dependent veins during sympathetic venoconstriction. Second, the stress of competition leads to elevated circulating catecholamines, which will exert some constrictor effect on the cerebral arterioles. Third, most weight lifters hyperventilate immediately before a lift. This produces hypocapnia, which lowers the cerebral interstitial proton concentration. Protons constitute the single most powerful metabolic dilator influence on the cerebral arterioles, so hypocapnia causes significant cerebral vasoconstriction.

Dependence on evaporative cooling

As discussed in Chapter 9 (p. 106), the internal heat generated by even intense prolonged exercise produces only moderate hyperthermia, so long as there is effective evaporative cooling by sweat. By definition, therefore, anything that interferes with heat loss is likely to result in excessive elevation of body temperature. If this rises to more than 41° C (106° F) then central nervous function begins to be impaired, with permanent brain damage or death occurring at only slightly higher temperatures.

Sweat is a highly effective source of heat loss when air humidity is low. This is illustrated dramatically by our capacity to maintain a near-normal core temperature in sauna baths, where the temperature is routinely set at around 100° C (212° F), but relative humidity is around 10% or less. However, the efficiency of evaporative heat loss is highly dependent on absolute relative humidity, as witnessed by the greatly increased sweat production produced by quite small increments in sauna humidity when one pours water on the coals. If environmental relative humidity is 90% or more, as is often the case in many tropical climates, then virtually no sweat evaporates and there is consequently almost no benefit for heat loss, despite the fact that the volume of sweat secreted for a given workload and ambient temperature is much greater than under less humid conditions (Fig. 10.2). Under these circumstances, heat loss depends almost entirely on radiation and convection, which are far less efficient than evaporation.

Figure 10.2 Diagrammatic representation of the effect of workload and ambient temperature on sweat production under conditions of low or high relative humidity. Note that for any given workload and air temperature, sweat production is higher in humid than in dry conditions.

Heat exhaustion

In the absence of fluid replacement, plasma volume falls during exercise in line with the volume of sweat produced. Below a critical volume, it becomes impossible to maintain blood pressure in the face of the overall low peripheral resistance imposed by dilatation in muscle and cutaneous beds. As a result, cerebral perfusion is prejudiced in the upright posture and the individual collapses. The time to onset of this state of heat exhaustion will be determined primarily by the rate of sweating and, therefore, depends on workload and on environmental temperature and humidity. Under competitive conditions, it can also be prolonged by motivation, to the extent that collapse does not occur until fluid depletion is so great that sweat production has begun to decline.

Since evaporative heat loss continues to be effective until at least shortly before onset of heat exhaustion, core temperature at the time of collapse from heat exhaustion is normal or only slightly elevated. However, it may rise more dramatically after collapse. Cessation of limb movement reduces convective and radiative heat loss, and even after muscle activity stops there is a large residual store of metabolic heat in the previously active muscle mass. Particularly when sweating is already decreased by fluid depletion, these factors can elevate core temperature to dangerously high levels.

Heat stroke

With normal evaporative heat loss, as discussed above, core temperature can be held close to the resting value even during intense work in hot environments, provided that plasma volume is maintained. If the efficiency of the evaporative heat loss pathway is impaired, however, exercise in the heat may elevate core temperature rapidly to values in excess of 40° C (104° F), resulting in heat stroke. Initially there is confusion, with reduced capacity for cognition and decision-making and at internal temperatures of around 41.5° C (107° F) consciousness is lost. At 42° C (108° F), sustained and often fatal damage to central neuronal structures occurs due to protein coagulation.

Individuals most susceptible to heat stroke during physical activity are, predictably, those in whom heat loss is minimized by insulative clothing and who are compelled to maintain a high level of work in a hot environment. Typical examples of this group are soldiers on route march and grid-iron footballers. As well, as discussed in the preceding section, it is important to remember that even when exercise stops heat will continue to enter the bloodstream from the previously active muscles. In situations of severe hyperthermia, where very small increments of core temperature can mean the difference between life and death, immediate and efficient removal of heat from the body is essential.

Tissue damage due to fluid depletion

Plasma volume depletion equivalent to reduction of total blood volume by 1.5 l or more is sufficient to reduce mean blood pressure even when sympathetic drive is maximal. In these circumstances, the consequent fall in tissue perfusion may have deleterious outcomes unless effective fluid replacement is achieved within 1–2 h. The problems occur mainly in regions of the circulation where microcirculatory counter-current exchange leads to local hypoxia (see Chapter 5, p. 58). In the kidney, the fall in medullary blood flow can cause necrotic damage to the loops of Henle and the collecting ducts, resulting in loss of urinary concentrating power and further fluid loss. In the small intestine, the fall in perfusion of the villi can result in sloughing of the villar epithelium, leading to exposure of the underlying tissue to intestinal proteolytic enzymes and to potential entry into the bloodstream of Gram-negative bacteria that are normally restricted to the gut lumen.

If blood pressure is low enough to prevent effective capillary perfusion through some areas of peripheral tissues, then blood cells begin to fall out of suspension and form clumps within the downstream venules (see Chapter 5, p. 60). Once this has occurred, even restoration of blood volume sufficient to reduce peripheral resistance to normal may not restore effective perfusion in these areas, because the venular cell clumps create a resistance sufficient to redirect blood flow to other, lower resistance, regions of the tissue.

Drug-induced hyperthermia

The 3,4-methylenedioxymethamphetamine molecule, commonly known as ecstasy, is widely used as a recreational drug and has been the cause of a number of deaths due to hyperthermia. Ecstasy has several pharmacological properties that collectively predispose to elevated core temperature (Mills et al 2004). First, it increases central sympathetic drive, with resulting cutaneous vasoconstriction. Second, it acts in a variety of tissues to stimulate uncoupling proteins. These uncouple mitochondrial respiration from ATP synthesis and so generate additional metabolic heat. Third, it appears to act on amine-receptive synapses in the hypothalamus to reset the central thermostat to a higher operating point.

Given this combination of excess heat production and reduced capacity for heat loss, it is not surprising that ecstasy can cause dangerous rises in core temperature in individuals who are also exercising. The risk is even greater for regular rather than for casual ecstasy users, since chronic ingestion up-regulates secretion of thyroid hormones and, therefore, elevates basal metabolic rate and heat production.

Exertional rhabdomyolysis

A small number of people have a defect in the RYR1 gene that encodes calcium channels in skeletal muscle sarcoplasmic reticulum. This can under some conditions result in excessive calcium entry to the sarcomeres during contraction and, therefore, more muscle heat production than normal. When these individuals undertake prolonged exercise, their core temperatures can rise to dangerous levels and the even greater elevation of local temperature in exercising muscles results in muscle cell breakdown (rhabdomyolysis). Even with adequate reversal of the hyperthermia, this situation can have fatal consequences, as the large amounts of liberated intracellular potassium impair cardiac rhythm and the liberated myoglobin is filtered in the kidney and may occlude the renal tubules, leading to acute renal failure.

Rhabdomyolysis has as well been reported as a consequence of ecstasy intoxication, presumably in individuals with similar genotypic predispositions. Because the abnormal calcium channel function appears to only occur during prolonged muscle activation, short bouts of even intense exercise do not generate excessive heat and so are not associated with risk of hyperthermic damage (Muldoon et al 2004).