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CLINICAL RESEARCH: AUTONOMIC FUNCTION

Angiotensin-Converting Enzyme Genotype Predicts Cardiac and Autonomic Responses to Prolonged Exercise

Euan A. Ashley, MRCP, DPhil^_*,_*, Attila Kardos, MD, PhD, FESC, Ewan S. Jack, MB, ChB, FRCA, Walter Habenbacher, PhD, Mathew Wheeler, MD, PhD^||, Young M. Kim, BS^¶, Jeffrey Froning, MA^#, Jonathan Myers, PhD^_*, Gregory Whyte, PhD, FACSM^_**, Victor Froelicher, MD^_* and Pamela Douglas, MD, FACC, FASE

^_* Division of Cardiology, Stanford University, Stanford, California
^|| Division of Medicine, Stanford University, Stanford, California
Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
Department of Anaesthetics, University of Glasgow, Glasgow, Scotland
CNSystems, Graz, Austria
^¶ Department of Cardiovascular Medicine, University of Toronto, Toronto, Canada
^# Sunnyside Biomedical, Los Altos, California
^_** Director of Science and Research, English Institute of Sport, Manchester, United Kingdom
Ursula Geller Professor of Research in Cardiovascular Diseases and Cardiology Division, Duke University Medical Center, Durham, North Carolina.

Manuscript received October 8, 2005; revised manuscript received February 1, 2006, accepted February 21, 2006.

^_* Reprint requests and correspondence: Dr. Euan A. Ashley, Division of Cardiovascular Medicine, Falk CVRC, Stanford University, 300 Pasteur Drive, Stanford, California 94305. (Email: euan{at}stanford.edu).

OBJECTIVES: The purpose of this study was to investigate the phenomenon of left ventricular (LV) dysfunction after ultraendurance exercise.

BACKGROUND: Subclinical LV dysfunction in response to endurance exercise up to 24 h duration has been described, but its mechanism remains elusive.

METHODS: We tested 86 athletes before and after the Adrenalin Rush Adventure Race using echocardiography, impedance cardiography, and plasma immunoassay.

RESULTS: At baseline, athletes demonstrated physiology characteristic of extreme endurance training. After 90 to 120 h of almost-continuous exercise, LV systolic and diastolic function declined (fractional shortening before the race, 39.6 ± 0.65%; after, 32.2 ± 0.84%, p < 0.001; mitral inflow E-wave deceleration time before the race, 133 ± 5 ms; after, 160 ± 5 ms, n = 48, p < 0.001) without change in loading conditions as defined by LV end-diastolic dimension and total peripheral resistance estimated by thoracic impedance. There was a compensatory increase in heart rate (before, 55 ± 1.3 beats/min; after, 59 ± 1.5 beats/min, p = 0.05), which left cardiac output unchanged, as well as significant-but-subclinical increases in brain natriuretic peptide and troponin I. In addition, we found that athletes who were homozygous for the intron-16 insertion polymorphism of the angiotensin-converting enzyme (ACE) gene exhibited a significantly greater decrease in fractional shortening than athletes who were homozygous for the deletion allele. Heterozygotes showed an intermediate phenotype. In addition, the deletion group manifest an enhanced sympathovagal balance after the race, as evidenced by greater power in the low-frequency component of blood pressure variability.

CONCLUSIONS: The ACE genotype predicts the extent of reversible subclinical LV dysfunction after prolonged exercise and is associated with a differential postactivity augmentation of sympathetic nervous system function that may explain it.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   BRS = baroreceptor reflex sensitivity   BNP = brain natriuretic peptide   BP = blood pressure   HR = heart rate   LV = left ventricular

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