Resting heart rate often begins to fall after the first few sessions of regular dynamic exercise and may be around 10 beats/min lower than the pretraining value after 2 weeks of training (Murray et al 2006). This confers an immediate advantage on exercise capacity, since it increases heart rate reserve. A 20 year old with a resting heart rate of 70 beats/min can theoretically increase cardiac output by (200–70/70) or 1.85-fold by tachycardia alone: with a resting heart rate of 60 beats/min this increase becomes (200–60/60) or 2.33-fold. Thus, in order to undertake any given submaximal workload, the trained individual needs only to increase heart rate (and, therefore, cardiac workload) by (1.85/2.33) or 80% of the amount needed before training.

This early bradycardia is at least mainly a reflex result of the blood volume expansion induced by training, sensed as increased atrial filling by low-pressure baroreceptors and as increased stroke volume by high-pressure baroreceptors. A second contributing factor may be the reduction of sympathetic drive that results from repetitive central command (see Vascular adaptations, below). The magnitude of the early bradycardia does not appear to be affected greatly by training intensity and its relatively small magnitude has only a limited effect on work capacity, as shown by the calculations in the previous paragraph.

In individuals who train intensively for prolonged periods, much greater degrees of bradycardia develop due to increased vagal tone, such that resting heart rate may be as low as 35 beats/min. This obviously confers a far larger cardiac reserve, with the 20-year-old athlete being theoretically able to increase his cardiac output by (200–35/35) or 4.7-fold using tachycardia alone, and reducing his cardiac workload for a given submaximal work intensity to (1.85/4.7) or 40% of that in an untrained age-matched individual. This more dramatic bradycardic effect of prolonged training is secondary to structural adaptation of the heart (see Cardiac hypertrophy, below).

During incremental dynamic exercise, it has been found that many trained athletes do not produce linear increases in heart rate up to their age-limited maximum. Instead, the slope of the heart rate/work curve flattens at around 85% (Lepretre et al 2005). Since this workload corresponds approximately to the anaerobic threshold, the heart rate deflection point has been adopted in a number of centres as an easy, non-invasive monitor for setting training workloads. It has also been suggested that the deflection infers some advantage on athletes by allowing greater utilization of their capacity to increase cardiac output by increasing stroke volume, although no firm evidence base for this exists. Regardless of whether or not the phenomenon has a value, the mechanisms that underlie it are unknown, and its usefulness as a training aid is limited by its variable occurrence even in trained athletes.

Cardiac hypertrophy

Like skeletal muscle, the myocardium responds to chronically increased workload by muscle cell growth, resulting in what is traditionally known as the ‘athlete’s heart’ (Iglesias Cubero et al 2000). As in skeletal muscle, the pattern of growth varies depending on whether the increased work is dynamic or resistive. Increased ventricular filling (increased preload), with no change in outflow resistance, results in moderately thickened muscle around an enlarged ventricular chamber (eccentric hypertrophy). By contrast, increased resistance to outflow (increased afterload) due, for instance, to increased peripheral resistance, leads to a markedly thickened ventricular wall with no alteration of chamber size (concentric hypertrophy) (Fig. 11.2).

Figure 11.2 Hypertrophic changes of the ventricular myocardium in response to dynamic and resistive training. Dynamic training results in increased chamber size as well as wall thickening, while resistive training preferentially increases wall thickness with little or no increase in chamber size.

Chronic dynamic exercise exerts both of these effects on the heart; the increased preload, because of increased venous return, and the increased afterload, because of the pressor response to central command. Not surprisingly, therefore, the initial structural adaptations to dynamic training involve elements of both types of hypertrophy. In the right heart, little or no afterload increase takes place because the pulmonary vasculature is exempted from sympathetic vasoconstrictor influences and, in fact, pulmonary vascular resistance falls during exercise due to better ventilation/perfusion matching (see Chapter 8, p. 95). The right ventricle, therefore, shows uncomplicated eccentric hypertrophy. On the left side, however, there are increases in both preload and afterload, which induces some degree of concentric hypertrophy and limits the expansion of left ventricular chamber size until after around 6–9 months training. Thus, the full benefits of cardiac adaptation, in terms of increased stroke volume, are not evident until after this period.

From the preceding discussion, it should be obvious that static exercise has far less effect than dynamic exercise on resting stroke volume and heart rate, because it precludes ventricular chamber enlargement. This has some significance for the training of rowers, in whom massive elevation of cardiac reserve is essential for good performance, but who also experience large rises in afterload during the catch phase of the stroke. Training programmes, therefore, should not involve rowing alone, but include additional dynamic exercises devoid of resistive components.

The cardiac changes seen in concentric hypertrophy also bear consideration in relation to the implications for endocardial pressure. During contraction, the pressure within the ventricular wall rises with wall thickness, according to Laplace’s law, with the greatest pressure being in the endocardial layer. This means that coronary perfusion of the endocardium becomes less efficient as wall thickness rises, with greater potential for endocardial hypoxia and initiation of arrhythmias.

The progressive bradycardia that accompanies prolonged training tracks the development of ventricular hypertrophy and stroke volume increase. It is probably, therefore, at least partly due to baroreflex withdrawal of sinoatrial sympathetic drive and increased vagal drive, secondary to stroke volume increase. In addition, however, some evidence suggests that long periods of neurally induced bradycardia may result in changes in intrinsic sinoatrial membrane channel cycling, with resetting of the basic pacemaker potential slope to a lower gradient.

VASCULAR ADAPTATIONS

The resting bradycardia associated with training is accompanied by reduced total peripheral resistance. In studies that have tracked previously sedentary subjects through a training programme, the fall in peripheral resistance has been seen to cause a fall in mean resting blood pressure of up to around 10 mmHg (Murray et al 2006). There is, however, considerable variation between individuals in the magnitude of the effect and the available data suggest that little or no further effect on pressure occurs in highly trained athletes than is seen with moderately improved fitness. The fall in peripheral resistance that follows training may involve several mechanisms.

Sympathetic drive

In view of the apparent reduction in sympathetic vasomotor tone following acute exercise (see Chapter 7, p. 79) and the likely baroreflex effects of expanded blood volume, it might be expected that resting sympathetic drive would be reduced following training. In fact, microneurographic studies of action potential frequency in sympathetic nerve filaments provide no support for this, although for technical reasons these studies use muscle nerves and so give no information on the behaviour of, for example, splanchnic vasomotor control (Alvarez et al 2005).

There is, by contrast, good evidence that training reduces pressor responses to stimuli that cause sympathetic activation. Trained individuals have been found to exhibit less blood pressure rise in response to some laboratory stressors such as mental arithmetic and also to have less pronounced pressor responses to given increments of exercise. These changes may be due to reduced gain in the hindbrain responses to central command and could involve endorphin release (see Chapter 7, p. 85). Desensitization of peripheral metaboreceptors and limb mechanoreceptors may also be involved. In terms of training-mediated effects on performance, damping of sympathetic drive may be beneficial in allowing greater increments of muscle blood flow in response to local dilator factors during muscle activation (see Chapter 6, p. 72).

Endothelial function

Training is associated with increased endothelium-dependent dilator capacity, as indicated by the magnitudes of responses to reactive hyperaemia (see Chapter 6, p. 66) and by resting plasma levels of nitric oxide (NO). One possible mechanism is that the increased endothelial turnover caused by repetitive exercise-induced shear stress results in a systemic endothelial lining with a younger mean cell age that, therefore, has greater secretory capacity. There is evidence that endothelial function is affected preferentially in the vascular beds of those muscles that have been repetitively exercised (Thijssen et al 2005), so the extent of peripheral resistance reduction is likely to correlate with the proportion of the whole-body musculature that is used. This is an issue that needs to be considered when designing training programmes for patients with limited mobility.

Angiogenesis

With prolonged dynamic training, local release of vascular endothelial growth factor and other growth factors leads to sprouting of new capillaries and arterioles in the active skeletal muscles and the myocardium. Appearance of these new vessels necessarily lowers regional vascular resistance, as well as reducing the distance for diffusion of nutrients and metabolites between blood stream and cells. Much less effect on vascular resistance is seen with static or intense resistive training, since the capillary density in type IIb glycolytic muscle is considerably sparser than in oxidative muscles.

Arterial remodelling

It is not clear whether the angiogenic responses of the microcirculation to vascular growth factors are associated also with increased growth of large conducting arteries. If this occurred, it would cause a small but significant reduction in total peripheral resistance. To my knowledge, data are available only for the coronary vasculature. Isolated post-mortem findings have reported enlarged coronary arteries in elite athletes, but imaging studies of living athletes has not provided evidence that even intense training has an effect on resting diameters of the major coronary vessels.

THERMOREGULATORY ADAPTATIONS

Chronic exposure to either a hot external environment or to repetitive episodes of increased internal heat production, as occurs during dynamic exercise, results in the hypothalamic thermostat becoming more sensitive to inputs from central (blood) heat detectors. Compensatory heat loss processes are, therefore, activated with less displacement of core temperature from the set point, and cutaneous vasodilation and sweat secretion begin after shorter latency during an exercise bout. This reduces the amount of metabolic heat trapped in the body and so reduces the absolute rise in body temperature at any given workload. As well, the reduced volume of sweat required for heat loss reduces the need for cutaneous hyperaemia and so makes more blood flow available for muscle perfusion.

This is a further rapid thermoregulatory adaptation to result from the increased aldosterone secretion that follows exercise-induced hyperkalaemia (see above, p. 130). As in the renal tubules, aldosterone acts on sweat ducts to reabsorb sodium. In the presence of greater numbers of aldosterone receptors, therefore, the sodium content of sweat falls dramatically, from around 50 mmol/L in a sedentary exercising subject to around 5 mmol/L in a trained subject. Thus, although total water loss in sweat may rise in the trained individual, due to the greater amount of muscle work undertaken, plasma and extracellular fluid osmolality are maintained far more efficiently.

Figure 11.3 summarizes the adaptive responses to dynamic training, as discussed above.

Figure 11.3 The causes and results of adaptive cardiovascular responses to chronic dynamic exercise that lead to increased physical fitness.

GENDER DIFFERENCES

DETRAINING

The adaptive cardiovascular effects of training are lost if training ceases over timecourses that broadly reflect the times taken for their onset. Thus, plasma volume falls within a few days and whole blood volume over 2–3 weeks, with parallel reduction in maximum cardiac output. The increases in endothelial dilator capacity are also completely reversed by 2 weeks after training stops. The effect on achievable workload of short-term (of the order of weeks) training is, therefore, completely lost again within a matter of weeks, a fact that needs to be considered in relation to the potential long-term benefits of cardiac rehabilitation programmes.

After long-term (many months) training, by contrast, falls more gradually, as the reversals of muscle angiogenesis and cardiac hypertrophy take place over the order of months. Notwithstanding, there is some evidence that, in athletes who have trained for many years, some cardiac hypertrophy may persist permanently.

ROLE OF EXERCISE IN CARDIOVASCULAR THERAPY

Atherosclerosis as the main cause of cardiovascular disability

Together with cancer, cardiovascular disease represents the largest cause of mortality in Western societies. Almost all cases of death or incapacitation of cardiovascular origin are caused by atherosclerosis, a pathological process that involves fatty precipitates (atheromatous plaques) being deposited in large arteries at sites of endothelial damage. These plaques partially obstruct the arterial lumen, reducing nutritional blood flow. They may also be dislodged into the bloodstream as thrombi, where they travel to more distal sites and block the blood supply to areas of peripheral tissues, a process termed infarction.

Common sites of atherosclerotic damage

The tissues most sensitive to this local deprivation of flow are those with the greatest continuous need for oxygen – the myocardium and the brain. So the characteristic results of atheromatous thrombus formation are myocardial infarctions or heart attacks, and cerebral infarctions or strokes. The effect of less severe restriction of blood flow due to atherosclerotic luminal narrowing is most usually seen as chest pain when acidic metabolites accumulate in an area of the myocardium where coronary perfusion is reduced, causing stimulation of chemosensitive nerve endings. This type of pain caused by inadequate local blood flow is known as angina.

Plaques can also partially occlude the large arteries that supply the legs. The consequences of this reflect the fact that progressively smaller arteries contribute progressively more to regional vascular resistance. Thus, when there is moderate thrombotic obstruction to flow in the femoral or iliac arteries, blood flow to the legs is usually normal at rest, but the usual functional hyperaemia associated with exercise is impaired. This results in accumulation of acidic metabolites in the working muscle, with development of anginal leg pain after a short period of walking that makes the patient stop. The latency of onset of pain is related to the workload and, typically, the patient is able, after a short rest, to repeat a similar amount of exercise before the pain recurs. This pattern of periodic exercise-induced pain is termed intermittent claudication. When the same degree of thrombotic blockage occurs in one of the smaller, more distal arteries, there is reduced blood flow at rest, resulting in continual leg pain and ischaemic tissue damage (gangrene).

Hypertension predisposes to atherosclerosis

Long-term studies of the incidence of cardiovascular disease in large populations (epidemiological studies) have shown that atherosclerosis is more common in people who have relatively high blood pressures. The presence of high resting blood pressure (hypertension) has, therefore, become an independent predictive marker for heart attacks and strokes. Although guidelines vary across the world, the most common current threshold for hypertension is a resting blood pressure that is consistently higher than 140/90 mmHg. With this threshold, over 20% of all adults in Western societies are classified as hypertensive and, therefore, by definition require some sort of treatment – most usually pharmacological – in order to reduce their blood pressures.

The epidemiological evidence suggests that incidence of atherosclerosis is correlated with absolute blood pressure over the entire range of pressures that exist in man so, in theory, the lower the pressure, the less likely an individual is to sustain an adverse event. By this criterion, it would be advantageous to amend the current guidelines so as to reduce the pressure threshold for hypertension. However, the distribution of blood pressures in the community means that even lowering the threshold by 1 mmHg would result in an additional 1% of the population being classified as abnormal. Any benefits from reduced incidence of infarcts would have to be balanced against the massively increased costs of patient management. As well, there would be significant ethical questions about arbitrary classification of currently healthy individuals as patients and prescribing them drugs that have predictable side effects.

The increased risk of cardiovascular events associated with hypertension is probably related to the rapid increase in vessel wall tension as transmural pressure rises, in line with Laplace’s law (see Chapter 5, p. 52), since increased tension will facilitate breakdown of the endothelial barrier at sites of pre-existing cell damage and so aid plaque formation. High intravascular pressure will also, by increasing blood flow velocity, increase marginal shear stress in large arteries and facilitate dislodgement of pre-existing plaques. In addition, the increased cardiac afterload due to hypertension will lead to concentric hypertrophy of the left ventricle. This lowers coronary capillary density and increases systolic endocardial compression, reducing functional cardiac reserve and predisposing the heart to hypoxic damage.

Case history

A 58-year-old man, John J., was considering discontinuing his gym membership because his left calf ached when he exercised on the treadmill. He took up weight training instead, but 2 months later was still having pain during any prolonged exercise that required lower limb contractions. He was able to walk about 200 m without trouble, but after that his left leg ached so much that he had to stop. After a few minutes rest, he could walk the same distance again before the pain recurred.

In the exercise lab, measurements of blood flow were made in each of his calves, at rest and immediately after moderate cycle exercise (60 rpm, 80 W) until onset of pain (approx. 1 min). In his left and right legs respectively, resting flows were 2.4 and 2.6 ml/min/100 ml tissue and exercise flows were 8 and 18 ml/min/100 ml tissue.