Frontiers ReviewReduced maximal cardiac output at altitude — mechanisms and significance
Introduction
While it has been known since time immemorial that exercise capacity is reduced at altitude, the physiological underpinning of this impairment is not fully understood. It is certainly well known that exercise lasting more than a few seconds is critically dependent upon O2 availability to the muscle mitochondria, and that altitude of course reduces O2 availability by virtue of reduced barometric pressure and hence inspired PO2. Accordingly, it might at first be thought that O2 unavailability via reduced PO2 transmitted down the O2 transport system from air to mitochondria is a sufficient explanation for reduced exercise capacity, but many studies over the years have found a number of physiological effects of altitude that might, separately from a low PO2, affect O2 availability and thus exercise capacity. Some of these would act to preserve exercise capacity, others to diminish it.
Chief amongst these is hypoxic stimulation of breathing, without which extreme altitudes, such as the 8848 m summit of Mt. Everest, could never be attained. Thus, even if on Mt. Everest the lungs were perfectly homogeneous and moreover were not subject to diffusion limitation of O2 transport from alveoli to capillaries, the sea level arterial PCO2 of 40 Torr, if unchanged at altitude, would mandate an arterial PO2 of only about 3 Torr, clearly incompatible with life. Even this value would occur only if the respiratory exchange ratio was at least 1.0. Hyperventilation, therefore, acts to partly offset the effects of altitude on O2 transport.
A second well-known, if slower, accompaniment to high altitude is increased hemoglobin concentration from erythropoietin released by hypoxic kidney cells. For a given PO2 in the blood, the O2 concentration is increased in proportion to the rise in [Hb], which by and of itself should improve O2 transport and availability. However, high hematocrit means high blood viscosity and, as a result, the potential for reduced cardiac output (Richardson and Guyton, 1959).
A third consequence of spending time (days or weeks) at altitude is reduction in circulating plasma volume. In part, this is due to diuresis associated with the kidney’s attempt to excrete HCO3− ions to compensate for the respiratory alkalosis induced by hypoxia; in part, this comes from increased exhaled or sweated water in a low humidity environment; in part, this could also be caused by fluid losses from gastrointestinal disturbances not uncommon in primitive and hypoxic environments. While reduced plasma volume will raise [Hb] and thus O2 concentration in blood, cardiac filling pressures might fall and lead to reduced cardiac output and thus possibly reduced muscle blood flow. Convective O2 delivery to the muscles may thus be compromised.
Fourthly, autonomic nervous system changes have been found to occur on ascent to altitude (Richalet et al., 1992). Changes in sympathetic (Richalet et al., 1988) and parasympathetic activity (Kacimi et al., 1993) and in myocardial adrenoceptor density (Kacimi et al., 1992, Voelkel et al., 1981) have been discovered that could affect cardiovascular function, generally in the direction that would lead to a lower maximal cardiac output.
Fifthly, hypoxia at altitude could directly impair cardiac function. Just like skeletal muscle, the heart is critically dependent on O2 availability itself, so that at extreme altitudes such as the summit of Mt. Everest, where arterial PO2 is in the range of 25–30 Torr, one could well imagine myocardial hypoxia placing limits on cardiac function and thus cardiac output.
The foregoing clearly shows that several coexistent consequences of high altitude exposure exist, some acting to preserve and others to impair exercise capacity. Several of these have the potential of reducing cardiac output. Does this occur, what is/are the mechanism(s), and what is the consequence, if any, for exercise?
Section snippets
Cardiac output measurements at altitude
From the outset, one must separately consider acute altitude exposure, say hours to a couple of days, and chronic altitude exposure, lasting from a few days to several weeks. The latter is the focus of this review — indeed, acute altitude exposure will be discussed only briefly.
Acute exposures such as those associated with rapid (minutes to hours) ascent during altitude simulations in hypobaric chamber studies are limited to about 4500 m for safety reasons. Obviously, erythropoietin-related
Potential mechanisms of reduced maximal cardiac output
The introduction laid out several possible pathways that could lead to reduced maximal cardiac output based on what might be termed pathophysiological effects of altitude:
- 1.
Increased blood viscosity from erythrocytosis and increased hematocrit.
- 2.
Reduced cardiac filling pressures from reduced plasma volume.
- 3.
Autonomic changes such as increased parasympathetic or reduced sympathetic activity.
- 4.
Hypoxic myocardial dysfunction.
There is, however, a fifth possible mechanism that does not have a
Does the low maximal cardiac output at altitude contribute to the corresponding reduction in O2 max?
Even at sea level, one of the oldest and most contentious questions in the context of exercise continues to be “What determines maximal O2?” To cut to the quick, the traditional view holds that cardiac output is ‘the’ critical limiting factor (Barclay and Stainsby, 1975, Horstman et al., 1976). Thus, it is argued, O2 transport depends on the product of cardiac output, [Hb] and O2 saturation of Hb. Furthermore, comparing athletes to non-athletes, there is no systematic or at least
Acknowledgements
Supported by NIH HL17731.
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