Spontaneous "second wind" and glucose-induced second "second wind" in McArdle disease oxidative mechanisms

Ronald G. Haller, John Vissing

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Background: Blocked glycogen breakdown in McArdle disease impairs oxidative as well as anaerobic metabolism, but the contribution of impaired oxidative phosphorylation to everyday symptoms of McArdle disease remains poorly defined. Objective: To evaluate the oxidative implications of the spontaneous second wind and variables that influence the development of this typical feature of McArdle disease. Design: Assessment of exercise and oxidative capacity (VO2) before and after the spontaneous "second wind" and with a glucose infusion after a spontaneous second wind. Patients: Eight patients with complete myophosphorylase deficiency and 1 unique patient with 3% of normal myophosphorylase activity. Main Outcome Measures: Work capacity, VO2, heart rate, cardiac output. Results: All patients with complete myophosphorylase deficiency (1) had low peak VO2 (mean±SD, 13.0±2.0 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise; (2) achieved a spontaneous second wind with increased exercise capacity between 8 and 12 minutes of exercise due to a more than 25% increase in peak VO2 (16.5±3.1 mL · kg-1); and (3) with glucose infusion after a spontaneous second wind, experienced a further more than 20% increase in oxidative capacity (VO2, 19.9±3.9 mL · kg-1 min-1). In the patient with residual myophosphorylase, VO2 (22.2 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise was approximately 2-fold higher than the mean of patients lacking myophosphorylase, and no significant improvement in exercise and oxidative capacity accompanied prolonged exercise or glucose infusion. Conclusions: First, the spontaneous second wind and the glucose-induced second second wind in McArdle disease are due to substrate-dependent increases in muscle oxidative capacity. Second, by providing glycogen-derived pyruvate, a small amount of residual myophosphorylase activity normalizes the oxidative deficit of complete myophosphorylase deficiency and virtually eliminates the spontaneous second wind and glucose-induced second second wind.

Original languageEnglish (US)
Pages (from-to)1395-1402
Number of pages8
JournalArchives of Neurology
Volume59
Issue number9
DOIs
StatePublished - Sep 2002

Fingerprint

Glycogen Storage Disease Type V
Muscle Form Glycogen Phosphorylase
Exercise
Glucose
Glycogen
Anaerobiosis
Oxidative Phosphorylation
Pyruvic Acid
Cardiac Output
Heart Rate
Outcome Assessment (Health Care)
Muscles

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Spontaneous "second wind" and glucose-induced second "second wind" in McArdle disease oxidative mechanisms. / Haller, Ronald G.; Vissing, John.

In: Archives of Neurology, Vol. 59, No. 9, 09.2002, p. 1395-1402.

Research output: Contribution to journalArticle

@article{1332e389d0464331be46769256098212,
title = "Spontaneous {"}second wind{"} and glucose-induced second {"}second wind{"} in McArdle disease oxidative mechanisms",
abstract = "Background: Blocked glycogen breakdown in McArdle disease impairs oxidative as well as anaerobic metabolism, but the contribution of impaired oxidative phosphorylation to everyday symptoms of McArdle disease remains poorly defined. Objective: To evaluate the oxidative implications of the spontaneous second wind and variables that influence the development of this typical feature of McArdle disease. Design: Assessment of exercise and oxidative capacity (VO2) before and after the spontaneous {"}second wind{"} and with a glucose infusion after a spontaneous second wind. Patients: Eight patients with complete myophosphorylase deficiency and 1 unique patient with 3{\%} of normal myophosphorylase activity. Main Outcome Measures: Work capacity, VO2, heart rate, cardiac output. Results: All patients with complete myophosphorylase deficiency (1) had low peak VO2 (mean±SD, 13.0±2.0 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise; (2) achieved a spontaneous second wind with increased exercise capacity between 8 and 12 minutes of exercise due to a more than 25{\%} increase in peak VO2 (16.5±3.1 mL · kg-1); and (3) with glucose infusion after a spontaneous second wind, experienced a further more than 20{\%} increase in oxidative capacity (VO2, 19.9±3.9 mL · kg-1 min-1). In the patient with residual myophosphorylase, VO2 (22.2 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise was approximately 2-fold higher than the mean of patients lacking myophosphorylase, and no significant improvement in exercise and oxidative capacity accompanied prolonged exercise or glucose infusion. Conclusions: First, the spontaneous second wind and the glucose-induced second second wind in McArdle disease are due to substrate-dependent increases in muscle oxidative capacity. Second, by providing glycogen-derived pyruvate, a small amount of residual myophosphorylase activity normalizes the oxidative deficit of complete myophosphorylase deficiency and virtually eliminates the spontaneous second wind and glucose-induced second second wind.",
author = "Haller, {Ronald G.} and John Vissing",
year = "2002",
month = "9",
doi = "10.1001/archneur.59.9.1395",
language = "English (US)",
volume = "59",
pages = "1395--1402",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "9",

}

TY - JOUR

T1 - Spontaneous "second wind" and glucose-induced second "second wind" in McArdle disease oxidative mechanisms

AU - Haller, Ronald G.

AU - Vissing, John

PY - 2002/9

Y1 - 2002/9

N2 - Background: Blocked glycogen breakdown in McArdle disease impairs oxidative as well as anaerobic metabolism, but the contribution of impaired oxidative phosphorylation to everyday symptoms of McArdle disease remains poorly defined. Objective: To evaluate the oxidative implications of the spontaneous second wind and variables that influence the development of this typical feature of McArdle disease. Design: Assessment of exercise and oxidative capacity (VO2) before and after the spontaneous "second wind" and with a glucose infusion after a spontaneous second wind. Patients: Eight patients with complete myophosphorylase deficiency and 1 unique patient with 3% of normal myophosphorylase activity. Main Outcome Measures: Work capacity, VO2, heart rate, cardiac output. Results: All patients with complete myophosphorylase deficiency (1) had low peak VO2 (mean±SD, 13.0±2.0 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise; (2) achieved a spontaneous second wind with increased exercise capacity between 8 and 12 minutes of exercise due to a more than 25% increase in peak VO2 (16.5±3.1 mL · kg-1); and (3) with glucose infusion after a spontaneous second wind, experienced a further more than 20% increase in oxidative capacity (VO2, 19.9±3.9 mL · kg-1 min-1). In the patient with residual myophosphorylase, VO2 (22.2 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise was approximately 2-fold higher than the mean of patients lacking myophosphorylase, and no significant improvement in exercise and oxidative capacity accompanied prolonged exercise or glucose infusion. Conclusions: First, the spontaneous second wind and the glucose-induced second second wind in McArdle disease are due to substrate-dependent increases in muscle oxidative capacity. Second, by providing glycogen-derived pyruvate, a small amount of residual myophosphorylase activity normalizes the oxidative deficit of complete myophosphorylase deficiency and virtually eliminates the spontaneous second wind and glucose-induced second second wind.

AB - Background: Blocked glycogen breakdown in McArdle disease impairs oxidative as well as anaerobic metabolism, but the contribution of impaired oxidative phosphorylation to everyday symptoms of McArdle disease remains poorly defined. Objective: To evaluate the oxidative implications of the spontaneous second wind and variables that influence the development of this typical feature of McArdle disease. Design: Assessment of exercise and oxidative capacity (VO2) before and after the spontaneous "second wind" and with a glucose infusion after a spontaneous second wind. Patients: Eight patients with complete myophosphorylase deficiency and 1 unique patient with 3% of normal myophosphorylase activity. Main Outcome Measures: Work capacity, VO2, heart rate, cardiac output. Results: All patients with complete myophosphorylase deficiency (1) had low peak VO2 (mean±SD, 13.0±2.0 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise; (2) achieved a spontaneous second wind with increased exercise capacity between 8 and 12 minutes of exercise due to a more than 25% increase in peak VO2 (16.5±3.1 mL · kg-1); and (3) with glucose infusion after a spontaneous second wind, experienced a further more than 20% increase in oxidative capacity (VO2, 19.9±3.9 mL · kg-1 min-1). In the patient with residual myophosphorylase, VO2 (22.2 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise was approximately 2-fold higher than the mean of patients lacking myophosphorylase, and no significant improvement in exercise and oxidative capacity accompanied prolonged exercise or glucose infusion. Conclusions: First, the spontaneous second wind and the glucose-induced second second wind in McArdle disease are due to substrate-dependent increases in muscle oxidative capacity. Second, by providing glycogen-derived pyruvate, a small amount of residual myophosphorylase activity normalizes the oxidative deficit of complete myophosphorylase deficiency and virtually eliminates the spontaneous second wind and glucose-induced second second wind.

UR - http://www.scopus.com/inward/record.url?scp=0036716959&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036716959&partnerID=8YFLogxK

U2 - 10.1001/archneur.59.9.1395

DO - 10.1001/archneur.59.9.1395

M3 - Article

C2 - 12223025

AN - SCOPUS:0036716959

VL - 59

SP - 1395

EP - 1402

JO - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 9

ER -