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.

In this study we measured the central activation ratio (CAR) of the leg extensors and the elbow flexor muscles before and after exhaustive exercise in the heat to determine whether exercise-induced hyperthermia affects the CNS drive to exercised (leg extensors) and/or non-exercised (forearm flexors) muscle groups. Thirteen subjects exercised at fixed intensities representative of a percentage of peak power output (PPO) for 10 min periods (50 %, 40 %, 60 %, 50 %) and then at 75 % PPO until exhaustion in ambient conditions of 39.3 ± 0.8 °C and 60.0 ± 0.8 % relative humidity. Before and immediately following exercise subjects performed a series of maximal voluntary contractions (MVCs) with the leg extensors (exercised muscles) and forearm flexors (non-exercised muscles). The degree of voluntary activation during the sustained MVCs was assessed by superimposing electrical stimulation to the femoral nerve and the biceps brachii. Exercise to exhaustion increased the rectal temperature from 37.2 ± 0.2 to 38.8 ± 0.2 °C (P < 0.0001). The mean heart rate at the end of exercise to exhaustion was 192 ± 3 beats min-1. Leg extensor voluntary force was significantly reduced from 595 ± 143 to 509 ± 105 N following exercise-induced hyperthermia but forearm flexor force was similar before and after exercise. The CAR of the leg extensors decreased from 94.2 ± 1.3 % before exercise to 91.7 ± 1.5 % (P < 0.02) following exercise-induced hyperthermia. However, the CAR for the forearm flexors remained at similar levels before and after exercise. The data suggest that the central nervous system selectively reduces central activation to specific skeletal muscles as a consequence of exercise-induced hyperthermia. Experimental Physiology (2003) 88.6, 783-790.

In this study species-specific values for whole blood viscosity (WBV), plasma viscosity (PV) and erythrocyte aggregation (EA) were determined in a total of 360 animals. We used 40 individual adult animals of nine mammalian species: horse, pig, dog, cat, rat, cattle, sheep, rabbit and mouse. WBV measurements were carried out using a LS30 viscometer, PV was measured using OCR-D and EA was measured using a Myrenne aggregometer and the LS30 (aggregation index at low shear rate). At low shear rates (0.7 s-1 and 2.4 s-1) haematocrit (Hct)-standardized (40 % Hct) samples showed a higher value of WBV and EA in horse, pig, dog and cat. In cattle, sheep, rabbit and mouse, EA and WBV were markedly decreased and EA was almost undetectable, although the plasma fibrinogen concentration was higher in these animals. Rats showed the highest WBV at low shear rate in native blood and WBV was not different from horse in Hct-standardized blood; however, EA was very low in the rat, a result that might be explained by mechanical or geometrical properties of the red blood cell. EA correlated with the plasma protein concentration in each species except dog and mouse. In horse, cattle and pig, EA correlated with the plasma fibrinogen concentration. At high shear rate (94 s-1), WBV was higher in cattle than cat and rat, and dog had higher values than horse, suggesting specific interspecies differences depending on low shear and high shear values of WBV, as a result of mechanisms that influence RBC flexibility. PV was highest in cattle and lowest in rabbit and mouse and did not correlate with WBV. Haemorheological parameters differed between the species. Each species has its own rheological fingerprint. The physiological significance of these variations among mammalian species has not yet been established. Viscosity contributes to endothelial cell shear stress. While haemorheological parameters differ across the species it may be postulated that factors influencing flow-mediated endothelial cell signal transduction are different among the species. Experimental Physiology (2003) 88.3, 431-440.

Non-shivering thermogenesis in brown adipose tissue is the main mechanism for thermoregulatory heat production in small mammals and newborns. During cold acclimation the sympathetic innervation triggers the recruitment of brown adipose tissue by hyperplasia, which involves the proliferation and differentiation of precursor cells, and by hypertrophy of mature brown adipocytes. Mitochondrial biogenesis and increased synthesis of the uncoupling protein 1 (UCP-1) are hallmarks of the thermogenic recruitment process. The severalfold increase of mitochondrial protein content during cold acclimation recruits a large capacity for oxidative phosphorylation. However, UCP-1 increases proton leakage across the inner membrane of brown adipocyte mitochondria and thereby dissipates proton motive force as heat instead of ATP synthesis. During recent years considerable progress has been achieved in the analysis of transcriptional mechanisms controlling Ucp1 gene expression. However, so far only little is known about the molecular basis of cold-induced mitochondrial biogenesis in brown adipose tissue. Experimental Physiology (2003) 88.1, 141-148.

To our knowledge, the relationship between all four endogenous female sex hormones and resting cardiac autonomic function has not been studied. The aim of the current study was to examine the association between the normal endogenous levels of oestrogen (17β-oestradiol), progesterone, luteinising hormone and follicle-stimulating hormone and heart rate variability (HRV) during the menstrual cycle in young eumenorrheic women. Ten healthy, young, female subjects volunteered for this study. HRV and endogenous hormone levels were recorded at three phases of the menstrual cycle: menses (day 3.8 ± 0.5), ovulation (day 15.8 ± 0.7) and luteal (day 22.1 ± 0.4) to ensure HRV recordings at times of low (menses) and high (ovulation and luteal) hormonal influence. Heart rate recordings were obtained from supine resting subjects and analysed on a Holter analysis system. Total power (TP, 0-1.0 Hz), low frequency (LF, 0.041-0.15 Hz), high frequency (HF, 0.15-0.80 Hz) and LF/HF components of HRV were examined. Despite a significantly greater HR at ovulation and normal cyclic variations in all endogenous sex hormone levels, no measure of HRV was significantly different between menstrual cycle phases. Significant correlations between oestrogen levels and absolute measures of HRV at ovulation were identified. The results of the current study demonstrated that the normal cyclic variations in endogenous sex hormone levels during the menstrual cycle were not significantly associated with changes in cardiac autonomic control as measured by HRV. Significant correlation between peak oestrogen levels and HRV measures at ovulation provided further support for the reported cardioprotective effects of oestrogen in healthy females. Experimental Physiology (2003) 88.3, 441-446.

The metabolic and functional diversity of animal mitochondria caused by different mitochondrial compositions due to tissue-specific mitochondrial pathways and tissue-specific differences in expression of isoforms of subunits of enzymes participating in oxidative phosphorylation will be reviewed here. Applying the concept of metabolic control analysis, the relevance of this diversity for the explanation of tissue-specific effects observed in mitochondrial diseases with homoplasmic mitochondrial DNA mutations and nuclear-encoded respiratory chain defects is discussed. Experimental Physiology (2003) 88.1, 149-154.

Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. This review gives an overview of the principal clinical phenotypes and the molecular genetic basis of mitochondrial disorders identified so far. Experimental Physiology (2003) 88.1, 155-166.

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.

Radical oxygen species are a byproduct of normal energy metabolism in mitochondria. The short-lived radicals cause damage to their immediate surrounding, i.e. the mitochondria. While most of this damage will be removed by normal mitochondrial turnover, damage to mitochondrial DNA (mtDNA) can persist and may accumulate with age. Recent evidence indicates that mutant mtDNA molecules can accumulate within individual cells, potentially hampering mitochondrial function. Experimental Physiology (2003) 88.1, 167-174.

The origin of significant differences between the apparent affinities of heart mitochondrial respiration for exogenous ADP in isolated mitochondria in vitro and in permeabilized cardiomyocytes or skinned fibres in situ is critically analysed. All experimental data demonstrate the importance of structural factors of intracellular arrangement of mitochondria into functional complexes with myofibrils and sarcoplasmic reticulum in oxidative muscle cells and the control of outer mitochondrial membrane permeability. It has been shown that the high apparent Km for exogenous ADP (250-350 µM) in permeabilized cells and in ghost cells (without myosin) and fibres (diameter 15-20 µm) is independent of intrinsic MgATPase activity. However, the Km may be decreased significantly by a selective proteolytic treatment, which also destroys the regular arrangement of mitochondria between sarcomeres and increases the accessibility of endogenous ADP to the exogenous pyruvate kinase-phosphoenolpyruvate system. The confocal microscopy was used to study the changes in intracellular distribution of mitochondria and localization of cytoskeletal proteins, such as desmin, tubulin and plectin in permeabilized cardiac cells during short proteolytic treatment. The results show the rapid collapse of microtubular and plectin networks but not of desmin localization under these conditions. These results point to the participation of cytoskeletal proteins in the intracellular organization and control of mitochondrial function in the cells in vivo, where mitochondria are incorporated into functional complexes with sarcomeres and sarcoplasmic reticulum.Experimental Physiology (2003) 88.1, 175-190.