Michael J. Joyner

Endurance exercise performance: the physiology of champions

Efforts to understand human physiology through the study of champion athletes and record performances have been ongoing for about a century. For endurance sports three main factors – maximal oxygen consumption , the so‐called ‘lactate threshold’ and efficiency (i.e. the oxygen cost to generate a give running speed or cycling power output) – appear to play key roles in endurance performance. and lactate threshold interact to determine the ‘performance ‘ which is the oxygen consumption that can be sustained for a given period of time. Efficiency interacts with the performance to establish the speed or power that can be generated at this oxygen consumption. This review focuses on what is currently known about how these factors interact, their utility as predictors of elite performance, and areas where there is relatively less information to guide current thinking. In this context, definitive ideas about the physiological determinants of running and cycling efficiency is relatively lacking in comparison with and the lactate threshold, and there is surprisingly limited and clear information about the genetic factors that might pre‐dispose for elite performance. It should also be cautioned that complex motivational and sociological factors also play important roles in who does or does not become a champion and these factors go far beyond simple physiological explanations. Therefore, the performance of elite athletes is likely to defy the types of easy explanations sought by scientific reductionism and remain an important puzzle for those interested in physiological integration well into the future.

Influence of the Menstrual Cycle on Sympathetic Activity, Baroreflex Sensitivity, and Vascular Transduction in Young Women

BACKGROUND Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. METHODS AND RESULTS Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170+/-151 U/min; ML, 2252+/-251 U/min; P<0.001) and plasma norepinephrine levels (EF, 240+/-21 pg/mL; ML, 294+/-25 pg/mL; P=0. 025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, -4.15; FL, -5.42; P=0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. CONCLUSIONS The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.

Endurance Exercise as a Countermeasure for Aging

OBJECTIVE— We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. RESEARCH DESIGN AND METHODS— Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18–30 years old) and older (59–76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot. RESULTS— Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals. CONCLUSIONS— The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.

Effect of Various Lithotomy Positions on Lower-extremity Blood Pressure

Background Compartment syndrome of a lower extremity from hypoperfusion is a rare but potentially devastating complication of the lithotomy position during surgery. The aim of this study is to determine the effects of various lithotomy positions on lower‐extremity blood pressures. Methods Blood pressure in eight young, healthy people was studied for 10 lithotomy positions. Blood pressure measurements were taken in both the upper arm (brachial artery) and the lower extremity (dorsalis pedis). The heart‐to‐ankle height gradient in each position was measured, and a predicted lower‐extremity systolic pressure was calculated. The measured and predicted lower‐extremity systolic blood pressures were compared with repeated measures analysis of variance. Results As a group, the mean systolic blood pressures in the lower extremities correlated closely with the predicted values. However, the difference between measured and predicted pressures varied among the 10 positions (P < 0.05). Conclusions Although lower‐extremity systolic blood pressures in the young, healthy volunteers correlated with predicted values, there was an additional reduction in pressure associated with the lithotomy position. This surprising finding suggests that a lengthy procedure necessitating the use of a lithotomy position for only a portion should be planned so the remainder of the procedure can take place before establishing the position or so the position can be changed to an alternative position when it is no longer needed.

Exercise protects the cardiovascular system: effects beyond traditional risk factors.

In humans, exercise training and moderate to high levels of physical activity are protective against cardiovascular disease. In fact they are ∼40% more protective than predicted based on the changes in traditional risk factors (blood lipids, hypertension, diabetes etc.) that they cause. In this review, we highlight the positive effects of exercise on endothelial function and the autonomic nervous system. We also ask if these effects alone, or in combination, might explain the protective effects of exercise against cardiovascular disease that appear to be independent of traditional risk factor modification. Our goal is to use selected data from our own work and that of others to stimulate debate on the nature and cause of the ‘risk factor gap’ associated with exercise and physical activity.

Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans.

1. Our aim was to determine whether the vasodilating substance nitric oxide (NO) contributes to the rise in forearm blood flow observed during mental stress in humans. We also determined whether the NO might be released as a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow was measured in both forearms using plethysmography during several 3‐5 min bouts of a colour word test. In one forearm the nitric oxide synthase blocker NG‐monomethyl‐L‐arginine (L‐NMMA) and other drugs were infused via a brachial artery catheter. The contralateral forearm served as a control. 3. When L‐NMMA was given prior to mental stress it blunted the rise in blood flow in the treated forearm almost completely. The normal blood flow response returned during a second bout of stress conducted after a wash‐out period. During a third bout of mental stress, administration of more L‐NMMA again blunted the blood flow responses to mental stress. 4. When atropine was given prior to mental stress, the increases in blood flow were reduced in the treated forearm. Subsequent administration of both atropine and L‐NMMA caused a somewhat greater reduction in the blood flow responses than those observed with atropine alone. 5. These data demonstrate that NO plays a role in forearm vasodilatation during mental stress in humans. It is likely that most of the NO is released by cholinergic stimulation of the vascular endothelium.

Balance between cardiac output and sympathetic nerve activity in resting humans: role in arterial pressure regulation

Large, reproducible interindividual differences exist in resting sympathetic nerve activity among normotensive humans with similar arterial pressures, resulting in a lack of correlation between muscle sympathetic nerve activity (MSNA) and arterial pressure among individuals. Although it is known that the arterial pressure is the main short‐term determinant of MSNA in humans via the arterial baroreflex, the lack of correlation among individuals suggests that the level of arterial pressure is not the only important input in regulation of MSNA in humans. We studied the relationship between cardiac output (CO) and baroreflex control of sympathetic activity by measuring MSNA (peroneal microneurography), arterial pressure (arterial catheter), CO (acetylene uptake technique) and heart rate (HR; electrocardiogram) in 17 healthy young men during 20 min of supine rest. Across individuals, MSNA did not correlate with mean or diastolic blood pressure (r < 0.01 for both), but displayed a significant negative correlation with CO (r=−0.71, P= 0.001). To assess whether CO is related to arterial baroreflex control of MSNA, we constructed a baroreflex threshold diagram for each individual by plotting the percentage occurrence of a sympathetic burst against diastolic pressure. The mid‐point of the diagram (T50) at which 50% of cardiac cycles are associated with bursts, was inversely related to CO (r=−0.75, P < 0.001) and stroke volume (SV) (r=−0.57, P= 0.015). We conclude that dynamic inputs from CO and SV are important in regulation of baroreflex control of MSNA in healthy, normotensive humans. This results in a balance between CO and sympathetically mediated vasoconstriction that may contribute importantly to normal regulation of arterial pressure in humans.

Exercise and cardiovascular risk reduction: Time to update the rationale for exercise?

although it is generally accepted that the promotion of exercise accords with clinical best practice, the anecdotal experience of many primary care physicians, cardiologists, and exercise physiologists is that, even when exercise prescriptions are adhered to, risk factors often fail to demonstrate

Sex Differences in Sympathetic Neural-Hemodynamic Balance Implications for Human Blood Pressure Regulation

Among young normotensive men, a reciprocal balance between cardiac output and sympathetic nerve activity is important in the regulation of arterial pressure. In young women, the balance among cardiac output, peripheral resistance, and sympathetic nerve activity is unknown. Consequently, the aim of this study was to examine the relationship of cardiac output and total peripheral resistance to muscle sympathetic nerve activity in young women. Multiunit peroneal recordings of muscle sympathetic nerve activity were obtained in 17 women (mean±SEM: age 24±3 years) and 21 men (mean±SEM: age 25±5 years). Mean resting muscle sympathetic nerve activity was lower in women compared with men (19±3 versus 25±1 bursts minute−1; P<0.05), as was mean arterial pressure (89±1 versus 94±2 mm Hg; P<0.05). Mean arterial pressure was not related to muscle sympathetic nerve activity in men (P=0.80) or women (P=0.62). There was a positive relationship between total peripheral resistance and muscle sympathetic nerve activity (r=0.62; P<0.05) and an inverse relationship between cardiac output and muscle sympathetic nerve activity (r=−0.69; P<0.05) in men. Unexpectedly, muscle sympathetic nerve activity had no relationship to either total peripheral resistance (r=−0.27; P>0.05) or cardiac output (r=0.23; P>0.05) in women. Our results demonstrate that men and women rely on different integrated physiological mechanisms to maintain a normal arterial pressure despite widely varying sympathetic nerve activity among individuals. These findings may have important implications for understanding how hypertension and other disorders of blood pressure regulation occur in men and women.

Local inhibition of nitric oxide and prostaglandins independently reduces forearm exercise hyperaemia in humans

We tested the hypothesis that inhibition of synthesis of either nitric oxide (NO) or vasodilating prostaglandins (PGs) would not alter exercise hyperaemia significantly, but combined inhibition would synergistically reduce the hyperaemia. Fourteen subjects performed 20 min of moderate rhythmic forearm exercise (10% maximal voluntary contraction). Forearm blood flow (FBF) was measured by Doppler ultrasound. Saline or study drugs were infused (2 ml min−1) into the forearm via a brachial artery catheter to locally inhibit synthesis of NO and PGs during steady state exercise (NG‐nitro‐L‐arginine methyl ester (L‐NAME), 25 mg over 5 min to inhibit NO synthase (NOS); and ketorolac, 3 mg over 5 min to inhibit cyclooxygenase (COX)). After achieving steady state exercise over 5 min (control), L‐NAME was infused for 5 min, followed by 2 min saline, then by a 5 min infusion of ketorolac, and finally by 3 min of saline (n= 7). Drug order was reversed in seven additional subjects, such that single inhibition of NOS or COX was followed by combined inhibition. FBF during exercise decreased to 83 ± 2% of control exercise (100%) with NOS inhibition, followed by a transient decrease to 68 ± 2% of control during COX inhibition. However, FBF returned to levels similar to those achieved during NOS inhibition within 2 min (80 ± 3% of control) and remained stable through the final 3 min of exercise. When COX inhibition was performed first, FBF decreased transiently to 88 ± 4% of control (P < 0.01), and returned to control saline levels by the end of ketorolac infusion. Addition of L‐NAME reduced FBF to 83 ± 3% of control, and it remained stable through to the end of exercise. Regardless of drug order, FBF was ∼80% of steady state control exercise (P < 0.01) during the last 30 s of exercise. We conclude that (1) NO provides a significant, consistent contribution to hyperaemia, (2) PGs contribute modestly and transiently, suggesting a redundant signal compensates for the loss of vasodilating PGs, and (3) NO and PG signals appear to contribute independently to forearm exercise hyperaemia.