The purpose of the present study was to investigate the effect of temperature on the rates of isometric force development and relaxation in electrically activated fresh and fatigued human adductor pollicis muscle. Following immersion of the lower arm for 20 min in water baths of four different temperatures, muscle temperatures were approximately 37, 31, 25 and 22°C. Maximal isometric force was reduced by 16·8 ± 1·5 % at 22°C. The stimulation frequency-force and -rate of force development relationships were shifted to the left at lower temperatures. Q10 values for the maximal rates of force development and relaxation, and the times for 100 to 50 % and 50 to 25 % force relaxation, were about 2·0 between 37 and 25°C and about 3·8 between 25 and 22°C. However, the time for 50 to 25 % force relaxation had a relatively high Q10 value between 25 and 22°C (6·9) and this parameter also appeared to be more sensitive to fatigue compared to the other indices of relaxation. Nevertheless, the effect of fatigue on all parameters decreased with cooling over the entire (37-22°C) temperature range.

The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy - an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7 %; ID, 17.6 ± 2.2 %; DD, 14.9 ± 1.3 %, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function. Experimental Physiology (2000) 85.5, 575-579.

To effectively control bladder activity, and to treat urinary incontinence caused by bladder overactivity, identification of suitable targets for pharmacological intervention is necessary. Such targets may be found in the central nervous system (CNS) or peripherally. The causes of bladder overactivity are not known, but theoretically increased afferent activity, decreased inhibitory control in the CNS and/or peripheral ganglia, and increased sensitivity of the detrusor to efferent stimulation may be involved. Several CNS transmitters may modulate voiding, but few drugs with a defined CNS site of action have been developed for treatment of voiding disorders. Potentially, drugs affecting GABA, opioid, 5-HT, noradrenaline, dopamine, or glutamatergic receptors and mechanisms can be developed, but a selective action on the lower urinary tract may be difficult to obtain. Traditionally, drugs used for treatment of bladder overactivity have had a peripheral site of action, mainly the efferent neurotransmission or the detrusor muscle itself. Antimuscarinic drugs, β-adrenoceptor agonists, α-adrenoceptor antagonists, drugs affecting membrane channels, prostaglandin synthetase inhibitors and several other agents have been used. However, none of them has been developed specifically for treatment of bladder disorders, and their efficacy, as judged from controlled clinical trials (where performed), is often limited. Recent information on the α-adrenoceptor, β-adrenoceptor (β3), and muscarinic receptor subtypes of the human detrusor and outflow region can be the basis for the development of compounds with effect on bladder overactivity and with improved tolerance. New ways of decreasing acetylcholine release may represent a promising way of controlling bladder contraction. Potassium channel (KATP) openers are theoretically attractive, but the drugs available so far have targeted vascular rather than bladder smooth muscle, which has limited their clinical use. However, new drugs belonging to these groups with an interesting profile of action have been developed. Drugs decreasing afferent activity represent an attractive therapeutic approach and transmitters of afferent nerves and their receptors are possible targets for pharmacological interventions. Tachykinins, such as substance P, neurokinins A and B, and other neuropeptides have been demonstrated in nerves of the lower urinary tract and have been shown to influence bladder function. Agents affecting these nerves by causing release of tachykinins, such as capsaicin and resiniferatoxin, given intravesically can be effective in some cases of bladder overactivity, and agents antagonizing tachykinin receptors may also be of therapeutic interest.New drugs specifically directed for control of bladder activity are under development and will hopefully lead to improved treatment of urinary incontinence.This study was supported by the Swedish Medical Research Council (grant no. 6837).

In this review we discuss our current understanding of the cellular basis of uterine contractility, highlighting those areas requiring further study. It is clear that the basic processes of excitation-contraction coupling lie within the myometrial cell, and that these may be modified by agonists. Pacemaker acitivity, however, remains a mystery. The contribution of extracellular calcium entry to contraction is shown to be vital, whilst the role of the sarcoplasmic reticulum remains controversial. Much current experimental focus is on pathways controlling and regulating contraction, and we discuss sensitisation mechanisms and question their role in intact uterine preparations. Experimental Physiology (2001) 86.2, 239-246.

Recent epidemiological studies have shown that hypertensive men are more likely to undergo surgical intervention for irritative voiding symptoms from BPH than age-matched controls. Indeed, noradrenergic nerves which regulate vascular tone also participate in the functional component of bladder outlet obstruction due to BPH. Newer, less invasive therapies for BPH such as thermal therapy can relieve symptoms yet do not eliminate obstruction based on urodynamic studies. Coincidentally, drugs such as [alpha]-adrenoceptor antagonists, which have been thought to relieve obstruction due to a peripheral effect, can be given intrathecally in animals to relieve urinary frequency due to obstruction. Taken together these observations implicate both peripheral and central sympathetic pathways in the motor control of the urinary bladder especially with disease states.We have used the hypertensive and behaviourally hyperactive spontaneously hypertensive rat (SHR), to investigate the roles sympathetic pathways or micturition. Elevated nerve growth factor (NGF) derived from vascular and bladder smooth muscle cells of the SHR appears to direct morphological, biochemical, and functional changes. The increase in NGF can apparently be explained by stabilization of its mRNA leading to increased synthesis of NGF. Bladders from SHRs develop a profuse noradrenergic hyperinnervation compared with the control WKY strain. Since afferents supplying the SHR bladder are hypertrophied, changes in afferent pathways are also likely.These differences in innervation and NGF in the SHR may explain changes in function. SHRs void 3 times as frequently as their genetic controls. Urinary frequency can be reduced by [alpha]-adrenoceptor antagonists. Cystometrograms performed in SHRs reveal lower bladder capacities and micturition volumes and the presence of unstable contractions compared with the WKY rat. Intrathecal, rather than intra-arterial administration of the [alpha]-adrenoceptor antagonist doxazosin reduces unstable contractions in the SHR. In vitro muscle bath studies have shown enhanced responses of SHR bladder smooth muscle to [alpha]-adrenoceptor agonists.It is likely that upregulation of NGF production causes sensory and possibly noradrenergic pathways to elicit hyperactive voiding. Increase in NGF in the adult bladder due to pathological conditions yields similar, yet distinct, consequences for voiding behaviour and innervation. Likewise, increased NGF in adult bladders following obstruction or inflammation triggers neuronal hypertrophy, enhanced reflex activity and urinary frequency. In contrast to the SHR, hyper-innervation is not observed. Moreover, peripheral or spinal [alpha]-adrenoceptor blockade eliminates urinary frequency following obstruction. These observations support the role for sympathetic pathways in the motor function of the bladder, especially in congenital or adult disease states. A similar process may underlie the neuroplasticity involved in alterations after obstruction or inflammation of the lower urinary tract in humans. The SHR strain raises the possibility that a common genetic defect exists capable of predisposing to both hypertension and overactivity of the urinary bladder. Whether a genetic predisposition to sustained bladder overactivity in response to inflammatory stimuli in obstruction exists in humans is an intriguing prospect.

Painful stimuli can evoke dramatic responses in the cardiovascular and respiratory systems. We have assessed the role of both the sympathetic and parasympathetic nervous system in mediating the reflex tachycardia that accompanies somatic nociception. We describe a major role for the nucleus tractus solitarii (NTS) as a site for integrating nociceptive and cardiorespiratory afferents. Since cardiorespiratory and nociceptive afferents terminate in the NTS, this nucleus offers a powerful opportunity for central modulation. We show that the NTS plays a major role in mediating the reflex tachycardia evoked by somatic noxious stimulation. Similar noxious stimulation attenuates the cardiac component of the peripheral chemoreceptor reflex and inhibits the peripheral chemoreceptor-evoked excitatory synaptic response of some NTS neurones. The functional interpretation we propose is that by depressing homeostatic reflexes at the NTS, noxious stimulation-evoked cardiorespiratory changes can be expressed and maintained, which may be essential for the survival of the animal. Experimental Physiology (2002) 87.2, 259-266.

The variable pressure neck chamber has provided an invaluable research tool for the non-invasive assessment of carotid baroreflex (CBR) function in human investigations. The ability to construct complete stimulus-response curves and define specific parameters of the reflex function curve permits statistical comparisons of baroreflex function between different experimental conditions, such as rest and exercise. Results have convincingly indicated that the CBR stimulus-response curve is reset during exercise in an intensity-dependent manner to functionally operate around the prevailing pressure elicited by the exercise workload. Furthermore, both at rest and during exercise, alterations in stroke volume do not contribute importantly to the maintenance of arterial blood pressure by the carotid baroreceptors, and therefore, any reflex-induced changes in cardiac output (Q) are the result of CBR-mediated changes in heart rate. However, more importantly, the CBR-induced changes in mean arterial pressure (MAP) are primarily mediated by alterations in vascular conductance with only minimal contributions from Q to the initial reflex MAP response. Thus, the capacity of the CBR to regulate blood pressure depends critically on its ability to alter vascular tone both at rest and during exercise. This review will emphasize the utility of the variable pressure neck chamber to assess CBR function in human experimental investigations and the mechanisms by which the CBR responds to alterations in arterial blood pressure both at rest and during exercise. Experimental Physiology (2003) 88.6, 671-680.

Increasingly sophisticated and precise molecular genetic tools are applied to mice in order to study the cellular mechanisms underlying higher brain functions, including learning and memory. However, several studies have produced unclear or conflicting results. One reason for this is that performance in the behavioural tests used to assess learning and memory is influenced by various non-cognitive phenomena and can thus easily be affected by mutations through mechanisms unrelated to memory function. We conducted principal component analysis on data from 3003 mice tested using a standardized protocol to demonstrate this for the Morris swimming navigation test, one of the most widely used paradigms to assess memory and hippocampal function. In addition, we present a meta-analysis showing that genetic background and environment alone produce sufficient variation to span the range of most, if not all, behavioural variables and can thus easily mask or fake mutation effects if genetic studies are not designed properly. We suggest that the chance of obtaining useful results is maximized if behavioural deficits are differentiated by combining complementary behavioural protocols and by analysing multiple complementary parameters in each of them. Mutation effects must be contrasted statistically against the influences of genetic background and environment. In many situations, this is most efficiently achieved if (i) mutations are backcrossed to and maintained in one or (preferably) two well-characterized, commonly available inbred strains and (ii) if mutant and wild-type littermates are analysed on a hybrid or mixed genetic background, that is in F1 or F2 generations derived from the inbred stocks

The urinary bladder has only two functions, to store urine and to eliminate it from the body at socially convenient times. These functions depend on total integrity of the nervous system from brain to bladder. Many different neurotransmitter pathways are involved, modulating proper voluntary control over the reciprocal relationship between the storage function of the bladder and the outlet sphincters of the urethra. When voluntary control is lost or disrupted through neurological disease or damage then aberrant reflexes can take over resulting in incontinence. Such reflexes often involve the loss of those inhibitory mechanisms which normally suppress bladder contractions during the filling phase or sphincter contractions during the emptying phase. Treatment of incontinence by applied neuromodulation probably utilizes residual reflex pathways by which electrical stimulation can inhibit unwanted detrusor contractions or suppress the overactive urethral sphincter. With improvements in our understanding of the pathophysiology of voiding dysfunction, better diagnosis and the latest technical advances, for example, combining neuromodulation for detrusor hyper-reflexia with sacral anterior root stimulation for emptying the paralysed bladder (Brindley, 1988), we might hope to develop a new generation of implantable devices for treating people with incontinence (Craggs, 1997).There are still many gaps in our knowledge of neuromodulation of the lower urinary tract, for example we know little about the cerebral control of micturition in man. Such knowledge may be important for a better understanding of the many conditions we currently label 'idiopathic'. Future opportunities offered by functional magnetic resonance imaging and spectroscopy may help us to identify pathways and neurotransmitters in the brain of humans to complement the latest animal studies using transneuronal virus tracing to identify central micturition pathways.

Prior heavy exercise (above the lactate threshold, LT) reduces the amplitude of the pulmonary oxygen uptake (V˙O2) slow component during heavy exercise, yet the precise effect of prior heavy exercise on the phase II V˙O2 response remains to be established. This study was designed to test the hypotheses that (1) prior heavy exercise increases the amplitude of the phase II V˙O2 response independently of changes in the baseline V˙O2 value and (2) the effect of prior exercise depends on the amount of external work done during prior exercise, irrespective of the intensity of the prior exercise. Nine subjects performed two 6 min bouts of heavy cycling exercise separated by 6 min baseline pedalling recovery (A), two 6 min heavy exercise bouts separated by 12 min recovery (6 min rest and 6 min baseline pedalling, B), and a bout of moderate exercise (below the LT) in which the same amount of external work was performed as during the prior heavy exercise, followed by 6 min heavy exercise (C). In both tests A and B, prior heavy exercise significantly increased the absolute V˙O2 amplitude at the end of phase II (by ~150 ml min-1), and reduced the amplitude of the V˙O2 slow component by a similar amount. Following 12 min of recovery (B), baseline V˙O2, but not blood [lactate], had returned to pre-exercise levels, indicating that these effects occurred independently of changes in baseline V˙O2. Prior moderate exercise (C) had no effect on either the V˙O2 or blood [lactate] responses to subsequent heavy exercise. The V˙O2 response to heavy exercise was therefore dependent on the intensity of prior exercise, and the effects on the amplitudes of the phase II and slow V˙O2 components persisted for at least 12 min following prior heavy exercise. Experimental Physiology (2001) 86.3, 417-425.

Mammalian cardiomyocytes have limited regenerative capacity, such that cell death can result in a net loss of viable contractile elements and a decrease in cardiac functional reserve, both during normal ageing and after insults to the myocardium leading to heart failure. At least four types of cell death have been described, with apoptosis and necrosis being the most extreme phenotypes and most extensively studied. Many of the classical morphological and biochemical features associated with these forms of cell death have been derived from studies conducted in vitro and these may not always faithfully reflect events occurring in vivo. Before therapeutic interventions can be realistically developed, more studies need to be undertaken in vivo to simultaneously investigate these different death pathways, their control mechanisms and their relative contributions in depleting the pool of viable cardiomyocytes. We recently demonstrated immunohistochemically that a single injection of either a natural or synthetic catecholamine induces both cardiomyocyte apoptosis (identified by an anti-caspase 3 antibody) and necrosis (identified by an anti-myosin antibody) in the rat heart in vivo. After optimising the experimental conditions for hormone dose and temporal and spatial peaks of damage, the incidence of necrosis was 4-10 times greater than the incidence of apoptosis. Myocytes in the soleus muscle were also severely (7-10 %) damaged, involving both apoptosis and necrosis. In both striated muscles high levels of myocyte co-localisation for apoptosis and necrosis were observed, suggesting that secondary necrosis had occurred in most of the apoptotic myocytes in vivo. The ability of the catecholamines to cause myocyte death suggests that they might play an aetiological role in the progression of heart failure where over-activation of the sympathetic system results in sustained pathophysiological levels of these catecholamines. Experimental Physiology (2003) 88.3, 447-458.

It is well established clinically that the affective response to pain of deep origin (muscles, joints and viscera) is distinct from that evoked by cutaneous pain. Cutaneous pain triggers a fight-flight reaction (active emotional coping), whereas deep pain evokes a reaction of quiescence, decreased vigilance and vasodepression (passive emotional coping). These observations led to suggestions of distinct central representations for deep versus cutaneous pain. Indeed, studies using immediate early gene (c-fos) expression revealed selective activation of ventrolateral versus lateral columns of the midbrain periaqueductal grey region (PAG) by persistent pain of deep origin versus intermittent cutaneous pain. Ventrolateral versus lateral PAG activation had been found earlier to evoke passive versus active emotional coping. However, not all cutaneous pain triggers active coping. Persistent cutaneous pain (e.g. burns) instead, usually evokes passive coping. This raised the question of whether the behavioural significance of pain (i.e. its escapability versus inescapability), rather than its tissue origin, is represented in supraspinal regions such as the PAG. Subsequent study revealed that a persistent (inescapable) noxious cutaneous manipulation (clip of the neck) evoked both selective ventrolateral PAG Fos expression and passive emotional coping. Such data suggest that pain representation in the PAG reflects a quality akin to behavioural significance, rather than tissue origin. In contrast, in the spinal cord predominantly superficial dorsal horn Fos expression was seen after either persistent or intermittent noxious cutaneous stimuli, leaving the question of the pathway(s) via which persistent (inescapable) cutaneous pain activates the vlPAG unanswered. One experimental approach to this question is suggested. Experimental Physiology (2002) 87.2, 275-279.

Regulation of energy metabolism is one of the major functions of steroid hormones. In this process, mitochondria, by way of oxidative phosphorylation, play a central role. Depending on the energy needs of the cell, on the tissue, on the developmental stage and on the intensity of the hormonal stimulus, the response can be an activation of pre-existing respiratory chain components, an increased transcription of nuclear-encoded and/or mitochondrial-encoded respiratory chain enzyme (OXPHOS) genes and of biosynthesis of the respective enzyme subunits or, in extreme cases of high energy needs, an increase in the number of mitochondria and mitochondrial DNA content per cell. Some of the hormonally regulated systems involving effects on nuclear and mitochondrial OXPHOS genes are reviewed in this paper. The possible molecular mechanisms of steroid hormone action on nuclear and mitochondrial gene transcription and possible ways of coordination of transcription in these two separate cell compartments involving direct interaction of steroid receptors with hormone response elements in nuclear OXPHOS genes and in mitochondria and induction/activation of nuclear-encoded regulatory factors affecting mitochondrial gene transcription are presented. Experimental Physiology (2003) 88.1, 129-140.

Urinary outflow from the mammalian bladder occurs through the urethra. This outflow tract is a complicated structure composed of striated and smooth muscle and vascular urothelium. It is controlled by somatic and autonomic nerves and has several functions: it generates sustained tone to prevent urinary leakage during bladder filling; it generates transient reflex increases in pressure to prevent opening of the lumen when abdominal pressure rises; it undergoes relaxation preceding micturition and can generate urethral opening and shortening during micturition. A urethral pressure profile shows a peak pressure of [greater than or equal to] 100 cmH2O. The outermost coat is striated muscle, the striated or external sphincter. The fibres are predominantly circularly oriented. The extent varies in different species and between sexes. In the human female it extends the length of the urethra, and is composed mainly of slow twitch fibres. In the male, the sphincter extends from the membranous urethra over the base of the prostate and has nearly equal numbers of slow and fast twitch fibres. In both sexes, the posterior border may be deficient in striated muscle, and filled by circularly oriented smooth muscle. Activity in the slow twitch fibres through somatic nerves may be continuous during bladder filling. Outer circular and inner longitudinal smooth muscle is present Strips from either layer will generate sustained tone particularly if dissected from the high pressure zone. This tone is myogenic, and may be achieved in the absence of action potentials, but relies on influx of calcium through L-type calcium channels. Both layers receive sympathetic and parasympathetic excitatory innervation and nitrergic inhibitory innervation. Normal urethral pressure requires blood flow to the urothelium (lamina propria). Striated and smooth muscles are both thought to contribute to the resting urethral pressure in the human. The precise role of the smooth muscles during micturition is as yet unresolved.

The functional state of the lower urinary tract is monitored more or less continuously by afferent nerves, which provide a sensory input in the control of the bladder and the external urinary sphincter. The functional state of the former is regulated by the autonomic nerves to the bladder, principally the parasympathetic (pelvic) nerves, which cause the detrusor muscle to contract, and possibly also by the sympathetic (mainly hypogastric nerve) innervation, which may reduce the resting tone of the smooth muscle. Continence is normally maintained by the resistance of the urethral sphincters; the tone generated by the skeletal muscle external sphincter is under the control of the somatic [alpha]-motoneurones running in the pudendal nerve, and possibly some somatic efferents in the pelvic nerve of some species.

The regulation of myometrial contraction is of paramount importance for the maintenance of pregnancy and for parturition. Understanding this regulation involves delineating the pathways that control myometrial contraction and relaxation and defining the regulation of these pathways. The pathways can be broken down further into those signalling cascades controlling the concentration of intracellular free calcium (Ca2+i) and those controlling the contractile apparatus itself. This discussion focuses primarily on the former and their regulation during pregnancy. In particular, cross-talk between the contractant and relaxant signalling pathways mediated through cyclic AMP is markedly changed at the end of pregnancy. Experimental Physiology (2001) 86.2, 223-237.

In this review the evidence for structural adaptations of the coronary circulation in the healthy adult heart in response to exercise and training is examined. Previously, it was thought that expansion of the coronary arteries and resistance vasculature occurred without angiogenesis. Detailed studies of the time course of coronary vascular remodelling now reveal that capillary proliferation is an integral response to exercise training, but is disguised by concurrent transformation of capillaries into arterioles by 'arteriolarization'. Increases in numbers of small arterioles < 30 µm in diameter are accompanied by expansion in calibre of resistance and large coronary arteries. Stimuli related to increases in blood flow - shear stress and wall tension - and to mechanical deformation of the myocardium - stretch and compression - provide the main impetus for coronary vascular remodelling. Despite the technical difficulties of measuring such parameters in the heart in vivo, intervention studies using specific exercise components such as vasodilator, inotropic and chronotropic manipulations have allowed some insight into the differential regional effects of haemodynamic factors throughout the vascular tree. It remains to establish more clearly the involvement of mediators such as nitric oxide and growth factors in the temporal relationship to endothelial and smooth muscle growth and proliferation so that the endogenous attributes of exercise can be exploited for therapeutic purposes. Experimental Physiology (2003) 88.5, 645-658.

Spontaneous localised propagating waves of contraction and localised stretches have been reported to occur in the isolated whole bladder of the guinea pig. The physiological role and the cellular processes underlying these events are unknown. In order to gain insight into the mechanisms generating this complex activity, experiments were performed to examine and compare the responses of the whole bladder preparation to (i) the muscarinic agonists carbachol and arecaidine, (ii) the nicotinic ligand lobeline and (iii) nerve stimulation. High concentrations of the muscarinic agonists (>3 µM) induced a slow rise in intra-vesical pressure upon which were superimposed pressure transients, while low concentrations (< 300 nM) induced only phasic rises in pressure. One interpretation of these data is that there are two separate mechanisms activated by muscarinic agonists: one generating contracture and the other phasic activity. Immunocytochemical staining revealed M3 muscarinic receptors on smooth muscle cells within trabeculae and a second population of positive cells in the sub-urothelial layer. This observation raises the possibility that the actions of muscarinic agonists are a consequence of activating different cell types. Lobeline (1-60 µM) activated phasic contractions but did not cause a rise in basal pressure. Atropine did not inhibit the lobeline-induced responses but abolished the muscarinic responses. Also, hexamethonium or tetrodotoxin did not affect the lobeline-induced responses. These observations suggest that the mechanism generating phasic activity is activated by a nicotinic stimulus that does not involve ganglia, nerves or the neuromuscular junction. Stimulation of the bladder nerve at frequencies between 20 and 30 Hz for 5 s resulted in a rapid rise in intra-vesical pressure. Prolonged nerve stimulation (10-200 s) at frequencies between 1 and 10 Hz activated phasic rises in pressure. Low frequency nerve stimulation increased the frequency of agonist-induced phasic activity. Thus, nerve stimulation can also produce two forms of activity and low frequency stimulation can augment the processes generating phasic activity. These observations suggest that there are two distinct types of bladder activity: global contractions involving most of the bladder wall and phasic contractions comprising propagating waves of contraction. The mechanisms generating these contractile events appear to be different and they may involve cells located in different regions of the bladder. The nature of these mechanisms and their possible physiological significance is discussed. Experimental Physiology (2003) 88.3, 343-357.

Regular physical training is associated with several physiological and biochemical adaptations which enable an increase in cardiac output and widening of the systemic arterio-venous oxygen difference. An increase in cardiac chamber size is fundamental to the generation of a sustained increase in cardiac output for prolonged periods. Echocardiographic studies have shown that the vast majority of athletes have modest cardiac enlargement although a small proportion exhibit substantial increases in heart size. Recognised determinants of cardiac size include age, sex, ethnicity and type of sport. Cardiac dimensions vary considerably amongst athletes, even when allowances are made for these variables, suggesting that genetic, endocrine and biochemical factors also influence heart size. This review discusses the effects of age, sex, ethnicity and sporting discipline on cardiac dimensions in athletic individuals. Experimental Physiology (2003) 88.5, 665-669.