Author Archives: Paul Older

The time course of physiological adaptations to high-intensity interval training in older adults.

Herrod PJJ; Blackwell JEM; Boereboom CL; Atherton PJ; Williams JP; Lund JN; Phillips BE;

Aging medicine (Milton (N.S.W)) [Aging Med (Milton)] 2020 Sep 17; Vol. 3 (4), pp. 245-251. Date of Electronic Publication: 2020 Sep 17 (Print Publication: 2020).

Objective: High-intensity interval training (HIIT) has been shown to be more effective than moderate continuous aerobic exercise for improving cardiorespiratory fitness (CRF) in a limited time frame. However, the length of time required for HIIT to elicit clinically significant improvements in the CRF of older adults is currently unknown. The aim of this study was to compare changes in the CRF of older adults completing identical HIIT protocols of varying durations.
Methods: Forty healthy, community-dwelling older adults completed a cardiopulmonary exercise test (CPET) before and after 2, 4, or 6 weeks of fully supervised HIIT on a cycle ergometer, or a no-intervention control period.
Results: Anaerobic threshold (AT) was increased only after 4 (+1.9 [SD 1.1] mL/kg/min) and 6 weeks (+1.9 [SD 1.8] mL/kg/min) of HIIT (both P  < 0.001), with 6-week HIIT required to elicit improvements in VO 2 peak (+3.0 [SD 6] mL/kg/min; P  = 0.04). Exercise tolerance increased after 2 (+15 [SD 15] W), 4 (+17 [SD 11] W), and 6 weeks (+16 [SD 11] W) of HIIT (all P  < 0.001), with no difference in increase between the groups. There were no changes in any parameter in the control group.
Conclusion: Improvements in exercise tolerance from HIIT precede changes in CRF. Just 4 weeks of a well-tolerated, reduced-exertion HIIT protocol are required to produce significant changes in AT, with a further 2 weeks of training also eliciting improvements in VO 2 peak.

A Pilot Study on the Association of Mitochondrial Oxygen Metabolism and Gas Exchange During Cardiopulmonary Exercise Testing: Is There a Mitochondrial Threshold?

Baumbach P; Schmidt-Winter C; Hoefer J; Derlien S; Best N; Herbsleb M; Coldewey SM;

Frontiers in medicine [Front Med (Lausanne)] 2020 Dec 21; Vol. 7, pp. 585462. Date of Electronic Publication: 2020 Dec 21 (Print Publication: 2020).

Background: Mitochondria are the key players in aerobic energy generation via oxidative phosphorylation. Consequently, mitochondrial function has implications on physical performance in health and disease ranging from high performance sports to critical illness. The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allows in vivo measurements of mitochondrial oxygen tension (mitoPO 2 ). Hitherto, few data exist on the relation of mitochondrial oxygen metabolism and ergospirometry-derived variables during physical performance. This study investigates the association of mitochondrial oxygen metabolism with gas exchange and blood gas analysis variables assessed during cardiopulmonary exercise testing (CPET) in aerobic and anaerobic metabolic phases. Methods: Seventeen volunteers underwent an exhaustive CPET (graded multistage protocol, 50 W/5 min increase), of which 14 were included in the analysis. At baseline and for every load level PpIX-TSLT-derived mitoPO 2 measurements were performed every 10 s with 1 intermediate dynamic measurement to obtain mitochondrial oxygen consumption and delivery (mito V . O 2 , mito D . O 2 ). In addition, variables of gas exchange and capillary blood gas analyses were obtained to determine ventilatory and lactate thresholds (VT, LT). Metabolic phases were defined in relation to VT1 and VT2 (aerobic: <VT1, aerobic-anaerobic transition: ≥VT1 and <VT2 and anaerobic: ≥VT2). We used linear mixed models to compare variables of PpIX-TSLT between metabolic phases and to analyze their associations with variables of gas exchange and capillary blood gas analyses.
Results: MitoPO 2 increased from the aerobic to the aerobic-anaerobic phase followed by a subsequent decline. A mitoPO 2 peak, termed mitochondrial threshold (MT), was observed in most subjects close to LT2. Mito D . O 2 increased during CPET, while no changes in mito V . O 2 were observed. MitoPO 2 was negatively associated with partial pressure of end-tidal oxygen and capillary partial pressure of oxygen and positively associated with partial pressure of end-tidal carbon dioxide and capillary partial pressure of carbon dioxide. Mito D . O 2 was associated with cardiovascular variables. We found no consistent association for mito V . O 2 .
Conclusion: Our results indicate an association between pulmonary respiration and cutaneous mitoPO 2 during physical exercise. The observed mitochondrial threshold, coinciding with the metabolic transition from an aerobic to an anaerobic state, might be of importance in critical care as well as in sports medicine.


The Deconditioning Effect of the COVID-19 Pandemic on Unaffected Healthy Children.

Dayton JD; Ford K; Carroll SJ; Flynn PA; Kourtidou S; Holzer RJ;

Pediatric cardiology [Pediatr Cardiol] 2021 Jan 04. Date of Electronic Publication: 2021 Jan 04.

The COVID-19 pandemic has had devastating direct consequences on the health of affected patients. It has also had a significant impact on the ability of unaffected children to be physically active. We evaluated the effect of deconditioning from social distancing and school shutdowns implemented during the COVID-19 pandemic on the cardiovascular fitness of healthy unaffected children. This is a single-center, retrospective case-control study performed in an urban tertiary referral center. A cohort of 10 healthy children that underwent cardiopulmonary exercise testing after COVID-19 hospital restrictions were lifted was compared to a matched cohort before COVID-19-related shutdowns on school and after-school activities. Comparisons of oxygen uptake (VO 2 ) max and VO 2 at anaerobic threshold between the pre- and post-COVID-19 cohorts were done. The VO 2 max in the post-COVID cohort was significantly lower than in the pre-COVID cohort (39.1 vs. 44.7, p = 0.031). Only one out of ten patients had a higher VO 2 max when compared to their matched pre-COVID control and was also the only patient with a documented history of participation in varsity-type athletics. The percentile of predicted VO 2 was significantly lower in the post-COVID cohort (95% vs. 105%, p = 0.042). This study for the first time documented a significant measurable decline in physical fitness of healthy children as a result of the COVID-19 pandemic and its associated restrictions. Measures need to be identified that encourage and facilitate regular exercise in children in a way that are not solely dependent on school and organized after-school activities.

The clinical value of cardiopulmonary exercise testing in the modern era.

Laveneziana P; Di Paolo M; Palange P;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Jan 06; Vol. 30 (159). Date of Electronic Publication: 2021 Jan 06 (Print Publication: 2021).

Cardiopulmonary exercise testing (CPET) has long been used as diagnostic tool for cardiac diseases. During recent years CPET has been proven to be additionally useful for 1) distinguishing between normal and abnormal responses to exercise; 2) determining peak oxygen uptake and level of disability; 3) identifying factors contributing to dyspnoea and exercise limitation; 4) differentiating between ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular, metabolic and peripheral muscle causes of exercise intolerance; 5) identifying anomalies of ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular and metabolic systems, as well as peripheral muscle and psychological disorders; 6) screening for coexistent ischaemic heart disease, peripheral vascular disease and arterial hypoxaemia; 7) assisting in planning individualised exercise training; 8) generating prognostic information; and 9) objectively evaluating the impact of therapeutic interventions. As such, CPET is an essential part of patients’ clinical assessment. This article belongs to the special series on the “Ventilatory efficiency and its clinical prognostic value in cardiorespiratory disorders”, addressed to clinicians, physiologists and researchers, and aims at encouraging them to get acquainted with CPET in order to help and orient the clinical decision concerning individual patients.

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients.

Delsart P, Delahaye C, Devos P, Domanski O, Azzaoui R, Sobocinski J, Juthier F(, Vincentelli A, Rousse N, Mugnier A, Soquet J, Loobuyck V, Koussa M, Modine T, Jegou B, Bical A, Hysi I, Fabre O, Pontana F, Matran R, Mounier-Vehier C, Montaigne D.

Clin Cardiol. 2020 Dec 31. doi: 10.1002/clc.23537. Online ahead of print.

BACKGROUND: Although recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient’s physical rehabilitation and assess their cardiovascular prognosis. DESIGN: We aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed-up after acute aortic dissection. METHODS: Patients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow-up was done after CPET for new aortic event and major cardio-vascular events (MCE) not directly related to the aorta.
RESULTS: Among the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22-1.84) mlO2/beat, that is, 97 (83-113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow-up of 39(20-51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.
CONCLUSION: CPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.

Priming the cardiodynamic phase of pulmonary oxygen uptake through voluntary modulations of the respiratory pump at the onset of exercise

Experimental Physiology 28 December 2020


We examined how different breathing patterns can modulate venous return and alveolar gas transfer during exercise transients in humans. Ten healthy men transitioned from rest to moderate cycling while breathing spontaneously (SP) or with voluntary increases in abdominal (AB) or intrathoracic (RC) pressure swings. We used double body plethysmography to determine blood displacements between the trunk and the extremities (Vbs). From continuous signals of airflow and O2 fraction, we calculated breath‐by‐breath oxygen uptake at the mouth and used optoelectronic plethysmography to correct for lung O2 stores changes and calculate alveolar O2 transfer. Oesophageal (Poes) and gastric (Pga) pressures were monitored using balloon‐tipped catheters. Cardiac stroke volume was measured using impedance cardiography. During the cardiodynamic phase (Φ1) of ‐on kinetics (20 s following exercise onset), AB and RC increased total alveolar oxygen transfer compared to SP (227±32, p = 0.019 vs 235±27, p = 0.001 vs 206±20 ml, mean±SD). Pga and Poes swings increased with AB (by 24.4±9.6 cm H2O, p<0.001) and RC (by 14.5±5.7 cm H2O, p<0.001), respectively. AB yielded a greater increase in intra‐breath Vbs swings compared with RC and SP (+0.30±0.14 vs +0.16±0.11, p<0.001 vs +0.10±0.05 ml, p = 0.006) and increased the sum of stroke volumes compared to SP (4.47±1.28 vs 3.89±0.96 L, p = 0.053), while RC produced significant central blood translocation from the extremities compared with SP (by 493±311 ml, p<0.001). Our findings indicate that combining exercise onset with AB or RC increases venous return, thus increasing mass oxygen transport above metabolic consumption during Φ1 and limiting the oxygen deficit incurred.

Reference Values for Chronotropic Index from 1280 Incremental Cycle Ergometry Tests


Medicine & Science in Sports & Exercise: December 2020 – Volume 52 – Issue 12 – p 2515-2521

Clinical cardiopulmonary exercise testing can determine causes of exercise limitation. The slope of heart rate (fC) versus oxygen uptake (V˙O2), which we call the chronotropic index (CI), can help identify cardiovascular impairment. We aimed to develop a reference equation for CI based on a large number of subjects considered to have normal exercise responses.

From a database of 13,728 incremental cycle ergometry exercise tests, we identified 1280 normal tests based on the absence of a clinical diagnosis, normal body mass index, and normal aerobic performance plus absence of cardiovascular disease, medications, or ventilatory limitation. A linear mixed-model approach was used to analyze the relationship between CI and other variables.


Subjects were age 18–84 yr, and 693 (54.1%) were men. Mean ± SD CI in men was lower than in women, 41.2 ± 9.3 beats per liter versus 63.4 ± 15.7 L−1. Age (in years), sex (0, male; 1, female), height (in centimeters), and weight (in kilograms) were significant predictors for CI:CIi = 106.9 + 0.16 × agei + 14.3 × sexi − 0.31 × heighti − 0.24 × weighti. The SE of estimates ranged from 10.6 to 11.2 L−1 (median of 10.7 L−1).
We report a reference equation for CI derived from normal subjects. The CI can be used in conjunction with V˙O2max to interpret maximal cardiopulmonary exercise tests. We consider a high CI to be cardiovascular impairment and a low CI plus low V˙O2max to be chronotropic insufficiency.

Factors Contributing to Exercise Intolerance in Patients With Atrial Fibrillation.

Elliott AD; Verdicchio CV; Gallagher C; Linz D; Mahajan R; Mishima R; Kadhim K; Emami M; Middeldorp ME; Hendriks JM; Lau DH; Sanders P;

Heart, lung & circulation [Heart Lung Circ] 2020 Dec 16. Date of Electronic Publication: 2020 Dec 16.

Background: Reduced exercise capacity and exercise intolerance are commonly reported by individuals with atrial fibrillation (AF). Our objectives were to evaluate the contributing factors to reduced exercise capacity and describe the association between subjective measures of exercise intolerance versus objective measures of exercise capacity.
Methods: Two hundred and three (203) patients with non-permanent AF and preserved ejection fraction undergoing cardiopulmonary exercise testing (CPET) were recruited. Clinical characteristics, AF-symptom evaluation, and transthoracic echocardiography measures were collected. Peak oxygen consumption (VO2peak ) was calculated during CPET as an objective measure of exercise capacity. We assessed the impact of 16 pre-defined clinical features, comorbidities and cardiac functional parameters on VO2peak .
Results: Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO2peak was 20.3±6.3 ml/kg/min. 24.9% of patients had a VO2peak considered low (<16 ml/kg/min). In multivariable analysis, echocardiography-derived estimates of elevated left ventricular (LV) filling pressure (E/E’) and reduced chronotropic index were significantly associated with lower VO2peak . The presence of AF at the time of testing was not significantly associated with VO2peak but was associated with elevated minute ventilation to carbon dioxide production indicating impaired ventilatory efficiency. There was a poor association between VO2peak and subjectively reported exercise intolerance and exertional dyspnoea.
Conclusion: Reduced exercise capacity in AF patients is associated with elevated LV filling pressure and reduced chronotropic response rather than rhythm status. Subjectively reported exercise intolerance is not a sensitive assessment of reduced exercise capacity. These findings have important implications for understanding reduced exercise capacity amongst AF patients and the approach to management in this cohort.

Heart rate recovery in patients with hypertrophic cardiomyopathy.

Patel V; Critoph CH; Finlay MC; Mist B; Lambiase PD; Elliott PM.

American Journal of Cardiology. 113(6):1011-7, 2014 Mar 15.

Recovery in heart rate (HR) after exercise is a measure of autonomic
function and a prognostic indicator in cardiovascular disease. The aim of
this study was to characterize heart rate recovery (HRR) and to determine
its relation to cardiac function and morphology in patients with
hypertrophic cardiomyopathy (HC).
We studied 18 healthy volunteers and 41
individuals with HC. All patients underwent clinical assessment and
transthoracic echocardiography. Continuous beat-by-beat assessment of HR
was obtained during and after cardiopulmonary exercise testing using
finger plethysmography. HRR and power spectral densities were calculated
on 3 minutes of continuous RR recordings.
Absolute HRR was lower in
patients than that in controls at 1, 2, and 3 minutes (25.7 +/- 8.4 vs
35.3 +/- 11.0 beats/min, p <0.001; 36.8 +/- 9.4 vs 53.6 +/- 13.2
beats/min, p <0.001; 41.2 +/- 12.2 vs 62.1 +/- 14.5 beats/min, p <0.001,
respectively). HRR remained lower in patients at 2 and 3 minutes after
normalization to peak HR. After normalization to the difference in HR
between peak exercise and rest, HRR was significantly impaired in
individuals with obstructive HC at 3 minutes compared with controls. HR at
3 minutes correlated with peak left ventricular outflow tract gradient (B
0.154 beats/min/mm Hg, confidence interval 0.010 to 0.299, p = 0.037) and
remained a significant predictor of HRR after multivariable analysis.
Spectral analysis showed a trend toward an increased low-frequency to
high-frequency ratio in patients (p = 0.08) suggesting sympathetic
In conclusion, HRR is impaired in HC and correlates with the
severity of left ventricular outflow tract gradient. Prospective studies
of the prognostic implications of impaired HRR in HC are warranted.