Category Archives: Publications

Estimating Equations for Cardiopulmonary Exercise Testing Variables in Fontan Patients:…

Estimating Equations for Cardiopulmonary Exercise Testing Variables
    in Fontan Patients: Derivation and Validation Using a Multicenter
    Cross-Sectional Database

Butts, Ryan; Spencer, Carolyn; Jackson,
Lanier; Heal, Martha; Forbus, Geoffrey; Hulsey, Thomas; Atz, Andrew

Pediatric Cardiology, February 2015, Vol. 36 Issue: Number 2 p393-401,

Abstract: Cardiopulmonary exercise testing (CPET) is a common
method of evaluating patients with a Fontan circulation. Equations to
calculate predicted CPET values are based on children with normal
circulation. This study aims to create predictive equations for CPET
variables solely based on patients with Fontan circulation. Patients
who performed CPET in the multicenter Pediatric Heart Network Fontan
Cross-Sectional Study were screened. Peak variable equations were
calculated using patients who performed a maximal test (RER > 1.1) and
anaerobic threshold (AT) variable equations on patients where AT was
adequately calculated. Eighty percent of each cohort was randomly
selected to derive the predictive equation and the remaining served as
a validation cohort. Linear regression analysis was performed for each
CPET variable within the derivation cohort. The resulting equations
were applied to calculate predicted values in the validation cohort.
Observed versus predicted variables were compared in the validation
cohort using linear regression. 411 patients underwent CPET, 166
performed maximal exercise tests and 317 had adequately calculated AT.
Predictive equations for peak CPET variables had good performance; peak
VO2, R2= 0.61; maximum work, R2= 0.61; maximum O2pulse, R2= 0.59. The
equations for CPET variables at AT explained less of the variability;
VO2at AT, R2= 0.15; work at AT, R2= 0.39; O2pulse at AT, R2= 0.34;
VE/VCO2at AT, R2= 0.18; VE/VO2at AT, R2= 0.14. Only the models for
VE/VCO2and VE/VO2at AT had significantly worse performance in
validation cohort. Of the 8 equations for commonly measured CPET
variables, six were able to be validated. The equations for peak
variables were more robust in explaining variation in values than AT

Effect of prehabilitation……….after neoadjuvant treatment in preoperative rectal cancer patients

Effect of prehabilitation on objectively measured physical fitness
after neoadjuvant treatment in preoperative rectal cancer patients: a
blinded interventional pilot study

West, M. A.; Loughney, L.;
Lythgoe, D.; Barben, C. P.; Sripadam, R.; Kemp, G. J.; Grocott, M. P.
W.; Jack, S..

BJA: British Journal of Anaesthesia, February 2015, Vol.
114 Issue: Number 2 p244-244, 1p;

Patients requiring surgery for locally advanced rectal cancer often
additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which
the effects on physical fitness are unknown. The aim of this
feasibility and pilot study was to investigate the effects of NACRT and
a 6 week structured responsive exercise training programme (SRETP) on
oxygen uptake at lactate threshold in such patients.
We prospectively studied 39 consecutive
subjects (27 males) with T3–4/N+ resection margin threatened rectal
cancer who completed standardized NACRT. Subjects underwent
cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0
(post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a
6 week SRETP on a training bike (three sessions per week) between week
0 and week 6 (exercise group). These were compared with 17
contemporaneous non-randomized subjects (control group). Changes in VO2 at theta
over time and between the groups were compared
using a compound symmetry covariance linear mixed model. Of 39 recruited subjects, 22 out of 22 (exercise)
and 13 out of 17 (control) completed the study. There were differences
between the exercise and control groups at baseline [age, ASA score
physical status, World Health Organisation performance status, and
Colorectal Physiologic and Operative Severity Score for the Enumeration
of Mortality and Morbidity (CR-POSSUM) predicted mortality]. In all
subjects,  VO2 at theta significantly reduced between
baseline and week 0 [−1.9 ml kg−1 min−1; 95% confidence interval (CI)
−1.3, −2.6; P</it><0.0001]. In the exercise group,
VO2 theta significantly improved between week 0 and week 6
(+2.1 ml kg−1 min−1; 95% CI +1.3, +2.9; P</it><0.0001), whereas the
control group values were unchanged (−0.7 ml kg−1 min−1; 95% CI −1.66,
+0.37; P</it>=0.204).

Conclusions NACRT before rectal cancer surgery reduces physical fitness. A structured exercise
intervention is feasible post-NACRT and returns fitness to baseline
levels within 6 weeks.

Cardiopulmonary exercise testing to evaluate the exercise capacity of patients with inoperable chronic thromboembolic pulmonary hypertension: An endothelin receptor antagonist improves the peak PETCO2

Hirashiki, Akihiro; Adachi, Shiro; Nakano, Yoshihisa; Kono, Yuji;
Shimazu, Shuzo; Shimizu, Shinya; Morimoto, Ryota; Okumura, Takahiro;
Takeshita, Kyosuke; Yamada, Sumio; Murohara, Toyoaki; Kondo, Takahisa.

Life Sciences, November 2014, Vol. 118 Issue: Number 2 p397-403, 7p;
Abstract: The 6-min walking distance is often used for assessing the
exercise capacity under the treatment with an endothelin receptor
antagonist (ERA) in patients with chronic thromboembolic pulmonary
hypertension (CTEPH). The cardiopulmonary exercise testing (CPX) was
reported to be more useful for the patients with pulmonary arterial
hypertension (PAH), however, few reports exist in patients with
inoperable CTEPH. The aim of this study was to investigate the effects
of an oral dual ERA, bosentan, on exercise capacity using CPX in
patients with PAH and inoperable CTEPH.;

Reference values for cardiopulmonary exercise testing in healthy adults: a systematic review

Paap, Davy; Takken, Tim.
Expert Review of Cardiovascular Therapy, December 2014, Vol. 12 Issue: Number 12 p1439-1453, 15p

Abstract: Reference values (RV) for cardiopulmonary exercise testing (CPET) provide the comparative basis for answering
important questions concerning the normality of exercise response in
patients and significantly impacts the clinical decision-making
process. The aim of this study is to systematically review the
literature on RV for CPET in healthy adults. A secondary aim is to make
appropriate recommendations for the practical use of RV for CPET.
Systematic searches of MEDLINE, EMBASE and PEDro databases up to March
2014 were performed. In the last 30 years, 35 studies with CPET RV were
published. There is no single set of ideal RV; characteristics of each
population are too diverse to pool the data in a single equation.
Therefore, each exercise laboratory must select appropriate sets of RV
that best reflect the characteristics of the population/patient tested,
and equipment and methodology utilized.

Putting lung function and physiology into perspective: cystic fibrosis in adults

Horsley, Alex; Siddiqui, Salman
Respirology, January 2015, Vol. 20 Issue: Number 1 p33-45, 13p
Abstract: Adult cystic fibrosis (CF) is notable for the wide heterogeneity in severity
of disease expression, both between patients and within the lungs of
individuals. Although CFairways disease appears to start in the small
airways, in adults there is typically widespread bronchiectasis,
increased airway secretions, and extensive obstruction and inflammation
of the small airways. The complexity and heterogeneity of airways
disease in CFmeans that although there are many different methods of
assessing and describing lung ‘function’, none of these
single‐dimensional tests is able to provide a comprehensive assessment
of lung physiology across the spectrum seen in adult CF. The most
widely described measure, the forced expiratory volume in 1 s, remains
a useful and simple clinical tool, but is insensitive to early changes
and may be dissociated from other more detailed assessments of disease
severity such as computed tomography. In this review, we also discuss
the use of more sensitive novel assessments such as multiple breath
washout tests and impulse oscillometry, as well as the role of
cardiopulmonary exercise testing. In the future, hyperpolarized gas
magnetic resonance imaging techniques that combine regional structural
and functional information may help us to better understand these
measures, their applications and limitations.;

The global peripheral chemoreflex drive in patients with systemic sclerosis: a rebreathing and exercise study

Ninaber, M.K.; Hamersma,
W.B.G.J.; Schouffoer, A.A.; van ’t Wout, E.F.A.; Stolk, J.. QJM:

An International Journal of Medicine, January 2015, Vol. 108 Issue: Number
1 p33-33, 1p;


Background: Exercise intolerance (EI) in
systemic sclerosis (SSc) is difficult to manage by the clinician. The
peripheral chemoreflex drive compensates for metabolic acidosis during
exercise and may be related to EI. Aim: To assess the global peripheral
chemoreflex drive (GPCD) in patients with SSc at rest and during

Methods: Consecutively tested SSc patients (n = 49) were
evaluated by pulmonary function tests, carbon dioxide (CO2)
rebreathing studies and non-invasive cardiopulmonary exercise testing
(CPET). Results of their CO2 rebreathing tests were compared
with those of controls (n = 32). Respiratory compensation for
metabolic acidosis during CPET was defined by the occurrence of a sharp
increase in minute ventilation (VdotE) and the ventilatory equivalent
for CO2 (V’E and V’CO2) at the end of the
isocapnic buffer phase. Euoxic (eVHR) and hyperoxic (hVHR) ventilatory
responses to hypercapnia were measured and its difference (eVHR − hVHR)
was considered to reflect the GPCD. Results: In 45 patients with SSc,
CPET results showed respiratory compensation at the occurrence of
metabolic acidosis. eVHR − hVHR in patients with diffuse cutaneous SSc
(dcSSc) differed significantly from that in patients with limited
cutaneous SSc (lcSSc) and from that in controls (0.47 ± 0.38 (dcSSc)
vs. 0.90 ± 0.77 (lcSSc) and 0.90 ± 0.49 (controls) l/min/mmHg; P =
0.04 and P = 0.03, respectively).

Conclusions: Respiratory
compensation for metabolic acidosis occurred in all patients. However,
the GPCD was diminished in dcSSc patients, suggesting an altered
control of breathing. Its assessment may help the clinician to better
understand reported EI and exertional dyspnea in dcSSc patients.;

Arterial H+ regulation during exercise in humans

Karlman Wasserman, William L Beaver, Xing-Guo Sun, William Stringer

Resting arterial H+ concentration ([H+]a) is in the nanomolar range (40+/-2 nm/L) while its production is in the millimolar range/min, with little variation from subject to subject. To determin the precision with which [H+]a is regulated during exercise, [H+]a, PaCO2 and ventilation (Ve) were measured during progressively increasing work rate exercise in 16 normal subjects. (Ve) increased with [H+]a, the latter attributable to PaCO2 increase below the lactic acidosis threshold (LAT) (DVe/D[H+]a ~15 L min-1 nanomol-1). [H+]a and PaCO2 increased, simultaneously, as work rate was increased below LAT. PaCO2 reversed direction of change between LAT and ventilatory compensation point (VCP). Above LAT, [H+]a increase relative to (Ve) increase was greater than below LAT. PaCO2 decreased above the LAT, while [H+]a continued to increase. Thus the exercise acidosis was converted from respiratory, below, to a metabolic, above the LAT. We conclude that [H+]a is increased and regulated over the full range of exercise, but with less sensitivity above the LAT.

Respiratory Physiology & Neurobiology 178 (2011) 191-195

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Pulmonary O2 Uptake during Exercise: Conflating Muscular and Cardiovascular Responses

Brian J. Whipp, Susan A. Ward, and Harry B. Rossiter
Med. Sci. Sports Exerc., Vol. 37, No. 9, pp. 1574-1585, 2005 
For moderate-intensity exercise (below lactate threshold, thetaL), muscle O(2) consumption (VO(2)) kinetics are expressed in a first-order phase 2 (or fundamental) pulmonary O(2) uptake (VO(2)) response: dVO(2)/dt . tau + DeltaVO(2)((t)) = DeltaVO(2)((ss)); where DeltaVO(2)(ss) is the steady-state VO(2) increment, and tau the VO(2) time constant (which is within approximately 10% of tauQVO(2)). A likely source of VO(2) control in this intensity domain is ADP-mediated, for which intramuscular phosphocreatine (PCr) may serve as a proxy variable. Whether, in reality, this behavior reflects the operation of a single homogeneous compartment is unclear, however; a multicompartment structure comprised of units having a similar DeltaVO(2)((ss)) but with widely varying tau can also yield a “well-fit” exponential response with an apparent single tau. In support of this is the inverse (although poorly predictive) correlation between tau and both theta(L) and VO(2max). Above theta(L), the fundamental VO(2) kinetics are supplemented with a delayed, slowly developing component that can set VO(2) on a trajectory towards VO(2max), and that has complex temporal- and intensity-related kinetics. This VO(2) slow component is also demonstrable in [PCr], suggesting that the decreased efficiency above theta(L) predominantly reflects a high phosphate cost of force production rather than a high O(2) cost of phosphate production. In addition, the oxygen deficit for the slow component is more likely to reflect a progressive shifting of DeltaVO(2)((ss)) rather than a single DeltaVO(2)((ss)) having a single tau.

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Gas Exchange Responses to Constant Work-Rate Exercise in Patients with Glycogenosis Type V and VII

Hean-Yee Ong, Conor S. O’Dochartaigh, Sharon Lovell, Victor H. Patterson, Karlman Wasserman, D. Paul Nicholls, and Marshall S. Riley
Am J Respir Crit Care Med, Vol 169. pp 1238-1244, 2004 
During constant work-rate exercise above the lactic acidosis threshold, oxygen consumption fails to plateau by 3 minutes, but continues to rise slowly. This slow component correlates closely with the rise in lactate in normal subjects. We investigated if oxygen consumption during constant work-rate exercise could rise after 3 minutes in the absence of a rise in lactate. We studied five patients with McArdle’s disease, one patient with phosphofructokinase deficiency and six normal subjects. Subjects performed two 6-minute duration constant work-rate exercise tests at 40 and 70% of peak oxygen consumption. During low-intensity exercise, oxygen consumption reached steady state by 3 minutes in both groups. Lactate rose slightly in control subjects but not in patients. During high-intensity exercise, oxygen consumption rose from the third to the sixth minute by 144 (21-607) ml/minute (median and range) in control subjects and by 142 (73-306) ml/minute in patients (p = not significant, Mann-Whitney U test). Over the same period, lactate (geometric mean and range) rose from 2.68 (1.10-5.00) to 5.39 (2.70-10.00) mmol/L in control subjects, but did not rise in patients (1.20 [0.64-1.60] to 0.70 [0.57-1.20] mmol/L). We conclude that the slow component of oxygen consumption during heavy exercise is not dependent on lactic acidosis.

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Aerobically generated CO2 stored during early exercise

Chuang, M. L. Ting, H. Otsuka, T. et al
J Appl Physiol 87:1087-1097; 1999
Previous studies have shown that a metabolic alkalosis develops in the muscle during early exercise. This has been linked to phosphocreatine hydrolysis. Over a similar time frame, the femoral vein blood pH and plasma K(+) and HCO(-)(3) concentrations increase without an increase in PCO(2). Thus CO(2) from aerobic metabolism is converted to HCO(-)(3) rather than being eliminated by the lungs. The purpose of this study was to quantify the increase in early CO(2) stores and the component due to the exercise-induced metabolic alkalosis (E-I Alk). To avoid masking the increase in CO(2) stores by CO(2) released as HCO(-)(3) buffers lactic acid, the transient increase in CO(2) stores was measured only for work rates (WRs) below the lactic acidosis threshold (LAT). The increase in CO(2) stores was evident at the airway starting at approximately 15 s; the increase reached a peak at approximately 60 s and was complete by approximately 3 min of exercise. The increase in CO(2) stores was greater, but the kinetics were unaffected at the higher WR. Three components of the change in aerobically generated CO(2) stores were considered relevant: the carbamate component of the Haldane effect, the increase in CO(2) stores due to increase in tissue PCO(2), and the E-I Alk. The Haldane effect was calculated to be approximately 5%. Physically dissolved CO(2) in the tissues was approximately 30% of the store increase. The remaining E-I Alk CO(2) stores averaged 61 and 68% for 60 and 80% LAT WRs, respectively. The kinetics of O(2) uptake correlated with the time course of the increase in CO(2) stores; the size of the O(2) deficit correlated with the size of the E-I Alk component of the CO(2) stores. We conclude that a major component of the aerobically generated increase in CO(2) stores is the new HCO(-)(3) generated as phosphocreatine is converted to creatine.

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