Dr Richard Clements

Cardiovascular responses of older adults to downhill (DTW, -10% incline) and level treadmill walking (0%) at self-selected walking speed (SSWS) were examined. Fifteen participants (age 68 ± 4 yr, height 1.69 ± 0.08 m, body mass 74.7 ± 8.1 kg) completed two 15-min walks at their SSWS (4.6 ± 0.6 km/hr). Cardiovascular responses were estimated using an arterial-volume finger clamp and infrared plethysmography. Oxygen consumption was 25% lower during DTW and associated with lower values for stroke volume (9.9 ml/beat), cardiac output (1.0 L/min), arteriovenous oxygen difference (a-v O2 diff, 2.4 ml/L), and systolic blood pressure (10 mmHg), with no differences in heart rate or diastolic and mean arterial blood pressure. Total peripheral resistance (TPR) was higher (2.11 mmHg) during DTW. During downhill walking, an exercise performed with reduced cardiac strain, endothelial changes, and reduced metabolic demand may be responsible for the different responses in TPR and a-v O2 diff. Future work is warranted on whether downhill walking is suitable for higher risk populations.

Introduction. Cardiovascular function declines with increasing age. Most studies examining this phenomenon have not dissociated superimposed disease from normal healthy ageing. Aims. To determine the impact of normal healthy ageing on overall cardiac function, and the efficacy of exercise in attenuating such changes. Methodology. Four groups of male subjects were investigated; sedentary 20-yr (n=7) and 50-yr (n=6) olds, very active 50-yr (n=9), and 50-yr old heart failure patients (n=7). Subjects completed three tests, maximal aerobic capacity (VO 2max), resting (CPOrest), and maximal (CPOmax) cardiac power output. Results. There were no significant differences between the groups in CPOrest (P>0.05). In contrast, CPOmax declined significantly over 30 years of healthy ageing, and still further with heart disease. Long-term endurance training prevented these age-related decline in cardiac function. Conclusion. VO 2max, CPOmax and CR all decline over the course of healthy ageing, and are further accentuated in the failing heart. Exercise, and an active lifestyle, can attenuate these age-related changes.

Introduction The process of ageing is known to affect maximum oxygen consumption (VO2max) and some individual aspects of cardiac function (e.g. cardiac output; Q) in both men and women. In contrast, engaging in long-term endurance exercise can offset this decline in VO2max. Cardiac power output (CPO) has been established as the best measure of overall cardiac function (Cooke et al., 1998), integrating measurements of both blood pressure and blood flow. This is the first study to employ this method to examine the impact of long-term endurance exercise on cardiac function in women. Methods Two groups of women were recruited. Sedentary women (n=153), aged between 19 and 76 years, and veteran athletes (n=10) aged between 50 and 68 years. Furthermore the data from a group (n=72) of age-matched ( X = 58.4 ± 0.6 years) sedentary women were extracted to allow direct comparison to the athletic females. All procedures were approved by Liverpool John Moores University Ethics Committee and subjects gave their informed consent. After completing a health and medical questionnaire to ensure they were free from any known cardiovascular disease and confounding medications, all subjects completed a VO2max treadmill test. An incremental treadmill protocol was employed, and a 12-lead electrocardiogram was monitored throughout to detect any exercise induced abnormalities. To determine CPO, mean arterial pressure (MAP) and Q were measured at rest (CPOrest ) and at maximal exercise (CPOmax). Manual sphygmomanometry was used to measure blood pressure, and the non-invasive CO2 rebreathing techniques of Collier (1956) and Defares (1958) were employed to measure Q at rest and maximal exertion, respectively. Cardiac power output (in Watts) was calculated as (Q x MAP) x 2.22x10 -3 . Pearson’s correlation coefficient was used to examine any relationships over the full age range, with Anova and Tukey’s post-hoc test employed to compared the age-matched data. Statistical significance was defined as P < 0.01. Results While VO2max decreased with increasing age, the veteran athletes had a significantly higher VO2max than their agematched counterparts (Figure 1), and also possessed a significantly higher (38.7%) maximal arteriovenous oxygen difference (a- v O2 diff). Interestingly, both CPOrest and CPOmax failed to change significantly, either as a result of healthy ageing or participation in long-term exercise. Discussion/Conclusion The major novel findings of this study were that neither healthy ageing nor long-term endurance exercise had any significant impact on overall cardiac function in women. While the veteran athletes had a higher capacity to consume oxygen, this was mainly attributable to a higher peripheral extraction of oxygen, as illustrated by the a- v O2 diff. This is the first study to measure overall cardiac function in women. The results suggest that when compared to the male heart, the female heart is more resistant to the effects of ageing and endurance exercise.

The mammalian heart has a limited regenerative capacity (Anversa et al. 2002), so cardiomyocyte death, whether it occurs with normal ageing or ischaemic damage, results in a net loss of contractile cells. Furthermore, Olivetti et al. (1991) have reported a 33 % loss of cardiomyocytes between 20 and 70 years of age. This, together with a decrease in peak cardiac output, and blunted inotropic and chronotopic responses to catecholamines etc are known to occur with increasing age (Lakatta 2000). Cardiac power output (CPO) represents the overall function of the heart, measuring both its pressure and flow generating capacities. When determined at rest CPO (CPOrest) is around 1 watt (W) and like other indices of heart function fails to discriminate between age, fitness or heart failure (HF) (Fig. 1). It is only when the heart is maximally stimulated that true differences in CPO (CPOmax), and hence cardiac functional reserve (CR), become apparent (Fig. 1). To test the hypothesis that healthy ageing is associated with a decrease in CPOmax and CR, and that endurance training improves CPO, six groups of male subjects were studied (Fig. 1). Ethical approval was given by the university and all subjects signed a consent form. All subjects were screened (questionnaire) to ensure that they were free from known cardiovascular diseases and medications. Cardiac output (CO) and mean arterial pressure (MAP) were measured non-invasively using the CO2 rebreathe and auscultation methods respectively, at rest and at maximal exercise (Cooke et al. 1998) and CPO was calculated as (MAP X CO) X 2.22 X 10-3. CR was calculated from CPOmax - CPOrest. A one-way ANOVA was used to measure statistical significances between groups, with significance defined as P < 0.05, using a Tukey's post hoc analysis. CPOmax and CR declined significantly (P < 0.05) by 16 % and 18 %, respectively in sedentary (Sed) subjects between the ages of 20 and 60 years. These changes were accentuated in patients suffering from NY Class III HF (Fig. 1). In contrast to these effects of ageing, the veteran athletes (Tr) demonstrated significantly (P < 0.05) higher CPOmax and CR values than their 'age-matched' sedentary counterparts at both 50 and 60 years of age (Fig. 1). Of interest is the finding that these trained individuals exhibited similar or better cardiac function than the Sed 20 yr-old subjects. These results indicate that normal healthy ageing is associated with a reduction in overall cardiac function, represented by a decline in CPOmax and CR and that endurance training can ameliorate such changes in cardiac functional reserve. We are grateful to the British Heart Foundation for their support of this research Where applicable, experiments conform with Society ethical requirements

The purpose of this study was to determine the best scaling method to account for the effects of body size on measurements of overall cardiac function and subsequently the interpretation of data based on cardiac power output (CPO). CPO was measured at rest (CPOrest) and at maximal exercise (CPOmax) on 88 and 103 healthy but untrained men and women, respectively, over the age range of 20–70 yr. Cardiac reserve (CR) was calculated as CPOmax− CPOrest. CPOrest, CPOmax, and CR were all significantly related to body mass (BM), body surface area (BSA), and lean body mass (LBM). The linear regression model failed to completely normalize these measurements. In contrast, the allometric model produced size-independent values of CPO. Furthermore, all the assumptions associated with the allometric model were achieved. For CPOrest, mean body size exponents were BM0.33, BSA0.60, and LBM0.47. For CPOmax, the exponents were BM0.41, BSA0.81, and LBM0.71. For CR, mean body size exponents were BM0.44, BSA0.87, and LBM0.79. LBM was identified (from the root-mean-squares errors of the separate regression models) as the best physiological variable (based on its high metabolic activity) to be scaled in the allometric model. Scaling of CPO to LBMb(where b is the scaling exponent) dramatically reduced the between-gender differences with only a 7% difference in CPOrestand CPOmaxvalues. In addition, the gender difference in CR was completely removed. To avoid erroneous interpretations and conclusions being made when comparing data between men and women of different ages, the allometric scaling of CPO to LBMbwould seem crucial.

The purpose of this study was to determine the best scaling method to account for the effects of body size on measurements of overall cardiac function and subsequently the interpretation of data based on cardiac power output (CPO). CPO was measured at rest (CPOrest) and at maximal exercise (CPOmax) on 88 and 103 healthy but untrained men and women, respectively, over the age range of 20-70 yr. Cardiac reserve (CR) was calculated as CPOmax - CPOrest. CPOrest, CPOmax, and CR were all significantly related to body mass (BM), body surface area (BSA), and lean body mass (LBM). The linear regression model failed to completely normalize these measurements. In contrast, the allometric model produced size-independent values of CPO. Furthermore, all the assumptions associated with the allometric model were achieved. For CPOrest, mean body size exponents were BM

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The mechanical function of the heart is known to deteriorate with increasing age and disease. After rigorous screening of necropsied hearts to exclude cardiovascular disease, Olivetti et al1 in New York showed that about one third of the cardiomyocytes are lost from the human male heart between the ages of 17–90 years. This natural attrition contrasts with the loss incurred through myocardial infarction and cardiomyopathy, the most common causes of heart failure (HF) in western societies. We sought to identify whether the functional impacts of cardiac impairment through aging and HF are similar or different by conducting symptom limited cardiopulmonary exercise testing in conjunction with haemodynamic evaluations.

Various studies have shown that patients with severe growth hormone deficiency (GHD) have diverse changes in left ventricular (LV) size or performance but so far there is no direct indication of cardiac reserve ability to maintain the circulation during peak exercise. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls. Eighteen patients with severe GHD were studied and compared with 18 age‐, sex‐, and body mass index (BMI)‐matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive hemodynamic measurements during maximal cardiopulmonary exercise testing. Compared with matched controls, the cardiac power of GHD patients during exercise to volitional exhaustion was significantly reduced by 15% (mean ± SD: 4.4 ± 1.0 watts (W) vs. 5.2 ± 1.0 W, P= 0.02), despite attaining similar aerobic exercise peaks (VO2 max, GHD: 2390 ± 822 mL/min vs. controls: 2461 ± 872 mL/min, P= 0.80) and similar peak respiratory exchange ratios. The lower peak cardiac power could not be accounted for by peripheral alterations because both groups reached similar peak exercise systemic vascular resistances. Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate: 154 ± 21 bpm vs. 174 ± 11 bpm, P= 0.001) and a lower cardiac pressure‐generating capacity (systolic blood pressure [SBP] 160 ± 25 mmHg vs. 200 ± 15 mmHg, P < 0.0001). Using this robust noninvasive method of assessing functional cardiac pumping capacity we have for the first time shown that patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure‐generating capacity.

Aims: Cardiac resynchronization therapy (CRT) is a recognized treatment for appropriate patients. However, placement of the transvenous left ventricular lead is unsuccessful in 5–10% of patients and a further 20% fail to respond. For these groups, epicardial left ventricular lead placement is one alternative. We prospectively evaluated the effects of epicardial vs. transvenous placed CRT. Methods and results: Twenty-three subjects with unsuccessful transvenous coronary sinus lead placement underwent epicardial implantation. The subjects underwent clinical evaluation, cardiopulmonary exercise testing, and echocardiography before 3 and 6 months after. The results were compared with a control group (n = 35) who had received transvenous CRT. In both groups, there were significant improvements in all measures at 3 and 6 months. The improvement in peak VO2 was delayed in the epicardial group compared with the transvenous group. At 6 months, the improvements seen in all variables showed no difference between the groups. Conclusion: Epicardial lead placement is a viable option for patients with unsuccessful coronary sinus lead placement. The improvements in most variables were of a similar magnitude and over a similar time scale compared with transvenous placement. Improvements in peak VO2 were delayed in the epicardial group, probably as a result of a prolonged recovery time.

Summary

Introduction  Patients with severe GH deficiency (GHD) suffer with a reduced quality of life in addition to diverse changes in cardiac size and performance. So far, the cardiac reserve ability to maintain the circulation during peak exercise has not been measured. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls and that this could explain, in part, their reduced quality of life.

Aims  Eighteen patients with severe GHD and an assessment of GHD in adults (AGHDA) score ≥11 (mean 20·0, range 12–25) were studied and compared with 18 age‐, sex‐ and body mass index‐matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive haemodynamic measurements during maximal cardiopulmonary exercise testing.

Results  Compared with matched controls, the cardiac power of GHD patients during exercise to volitional exhaustion was significantly reduced by 15% (mean ± SD 4·4 ± 1·0 W vs. 5·2 ± 1·0 W, P = 0·02). Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate 154 ± 21/min vs. 174 ± 11/min, P = 0·001) and a lower cardiac pressure‐generating capacity (systolic blood pressure 160 ± 25 mmHg vs. 200 ± 15 mmHg, P < 0·0001). We found no correlation between any measure of peak cardiac power or function and the AGHDA score.

Conclusion  Using this robust noninvasive method of assessing functional cardiac pumping capacity, we have for the first time shown that, while patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure‐generating capacity, this does not correlate with their reduced quality of life assessed using the current standard AGHDA score.

Background: The impact of ageing on the human cardiovascular system has been the subject of several studies in recent years, but with insufficient emphasis on defining sex-specific differences. To rectify this, gender-specific differences in structure and function in the human cardiovascular system were studied in a European population during natural ageing. Methods: Cardiac power output (CPO) was measured and integrated with changes in left ventricular (LV) mass, diastolic, systolic and limb blood flow, blood pressure and exercise capacity in 93 health-screened men and 122 women, aged 20 to 75 years. Results: Correlating with a 21% loss of LV mass, maximum cardiac pumping (i.e. CPOmax = Q̇max x MAPmax) and reserve (CR = CPOmax - CPOrest) capacities decreased 20-25% with age in male hearts. In contrast, CPOmax, CR and LV mass were all preserved in ageing women. Maximum cardiac output (Q̇max; 26-32%), peak forearm blood flow (FBFpeak; 61%) and exercise capacity (40-50%) all decreased, but more so in men than women. In contrast, systemic vascular resistance (68-75%) and mean arterial pressure (MAPmax; 14-26%) increased in both sexes. CPOrest decreased 27% in men, but was unchanged in women, despite lower early:late diastolic filling (48-51%), Q̇rest (19-23%) and FBFrest (56%) in both sexes. Conclusions: Understanding sex-specific differences in cardiovascular ageing is important for public health and biomedical research, given increasingly larger older populations and the need to prevent and treat cardiovascular disease. © 2008 Elsevier Ireland Ltd. All rights reserved.

This study investigated the influence of age, sex, and aerobic capacity on resting and peak forearm and cutaneous blood flow (FBF, CBF). We recruited 93 female and 129 male subjects (age range 16-76 years). FBF and CBF were assessed by plethysmography and laser-Doppler flowmetry, respectively. Peak FBF was obtained following 5 min forearm vascular occlusion and peak CBF in response to local skin heating of 42°C. Blood pressure was measured manually and by Finapres. Maximal oxygen uptake (VO 2max) was obtained from a treadmill exercise stress test. Age was associated with declines in resting FBF (y = -1.176 ln(x) + 6.6899,r

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This study examined in older adults the effects of wearing the Cosmed K4b2 metabolic system with face mask during the 1‐mile Rockport Fitness Walking Test (RFWT). A randomised cross‐over design was used (13 males, 12 females, age: 67±4 (yrs). Walking time, walking speed and final heart rate were recorded and predicted VO2max calculated. Participants had a constant walking speed during the RFWT (P = 0.24) not influenced by wearing the Cosmed K4b2. Using Bland‐Altman analysis, bias for walking time, heart rate and predicted VO2max was not sig‐ nificant. The predicted VO2max wearing the Cosmed K4b2 was within 0.05±0.36 L∙min‐1. Wearing the Cosmed K4b2 metabolic system with face mask did not influence 1‐mile walking performance in older adults. This observa‐ tion allows the Cosmed K4b2 metabolic system to be used during walking tests in older adults to examine metabolic and physiologic adaptations by controlled exercise interventions.

The aim of the study was to examine whether self-selected walking speed during downhill treadmill walking by older adults would result in muscle injury and changes in physiological responses during level walking. Twenty-six participants (age: 67 ± 4 yrs; height: 1.69 ± 0.09 m; body mass: 74.9 ± 13.1kg) were assigned to level (n = 11, 30 min, 0%) or downhill walking (n=15, 30 min, -10%) at a self-selected walking speed. Self-selected walking speed and exercise intensity were similar for both groups (level: 4.2±0.4 km·hr-1, 42±6% VO2max; downhill: 4.6±0.6 km·hr-1, 44±15% VO2max). After 48-hours, downhill walking had reduced maximal voluntary isometric force of the m. quadriceps femoris (-15%, P<0.001), indicative of muscle injury, but no changes were observed for walking economy, minute ventilation, heart rate and respiratory exchange ratio during level walking. For older adults, downhill walking at a selfselected walking speed causes muscle injury without any detrimental effect on walking economy. Regular downhill walking at a self-selected walking speed by older adults is an eccentric endurance activity that may have the potential to improve cardiovascular fitness and muscle strength.

Age-associated decline in muscle mass and strength impairs functional mobility in older adults. We examined the effects of an eccentric endurance exercise programme (downhill treadmill walking, DTW) at a self-selected walking speed (SSWS) on functional mobility and eccentric and concentric strength of m. quadriceps femoris of older adults. Twenty-four older adults (67 ± 4 years) were randomly assigned to complete 3 × 30 min treadmill walks per week for 12 weeks on a level (n = 11, LTW 0%) or downhill (n = 13, DTW −10%) treadmill gradient at SSWS. SSWS was re-adjusted every 4 weeks. Participants were assessed for five repetition sit-to-stand (5-RSTS), maximal walking speed (MWS), timed up-and-go (TUG) and dynamic strength. SSWS was similar for both groups with increases from 1.18 ± 0.11 to 1.53 ± 0.09 m s−1 (LTW) and 1.26 ± 0.16 to 1.61 ± 0.12 m s−1 (DTW) (time, P < 0.01). Improvements in 5-RSTS, MWS and TUG were substantial and similar for both groups (time, P < 0.01). 5-RSTS (baseline LTW: 8.50 ± 1.19 s, DTW: 8.54 ± 1.52 s) improved by 32 and 34%. MWS (baseline LTW: 2.39 ± 0.38 m s−1, DTW: 2.40 ± 0.33 m s−1) improved by 22 and 23%. TUG (baseline LTW: 5.58 ± 0.51 s, DTW: 5.46 ± 0.89 s) improved by 22% for both groups. Peak eccentric and concentric torque did not change. Knee angle of concentric peak torque (180° s−1) was decreased after 12 weeks in both groups (LTW: 37° ± 16° to 26° ± 14°, DTW: 42° ± 18° to 37° ± 16°, P < 0.05). Regular level and downhill treadmill walking by older adults, at a SSWS, results in substantial improvements in functional mobility. Changes in functional mobility were not explained by changes in dynamic strength of the m. quadriceps femoris.

Cardiovascular responses of older adults to downhill (DTW, –10% incline) and level treadmill walking (0%) at self-selected walking speed (SSWS) were examined. Fifteen participants (age 68 ± 4 yr, height 1.69 ± 0.08 m, body mass 74.7 ± 8.1 kg) completed two 15-min walks at their SSWS (4.6 ± 0.6 km/hr). Cardiovascular responses were estimated using an arterial-volume finger clamp and infrared plethysmography. Oxygen consumption was 25% lower during DTW and associated with lower values for stroke volume (9.9 ml/beat), cardiac output (1.0 L/min), arteriovenous oxygen difference (a-v O2 diff, 2.4 ml/L), and systolic blood pressure (10 mmHg), with no differences in heart rate or diastolic and mean arterial blood pressure. Total peripheral resistance (TPR) was higher (2.11 mmHg) during DTW. During downhill walking, an exercise performed with reduced cardiac strain, endothelial changes, and reduced metabolic demand may be responsible for the different responses in TPR and a-v O2 diff. Future work is warranted on whether downhill walking is suitable for higher risk populations.