title: Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation-contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure.
abstract: The development of muscle fatigue due to exhaustive exercise is associated with impaired sarcoplasmic reticulum (SR) Ca-transport activity. This study tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue owing to relative functional overload regardless of the method of induction: excessive stimulation, diminished performance capacity, or excessive excitation-contraction coupling. The Ca-transport activity was determined using three unique models of muscle fatigue: chronic and rapid ventricular pacing in dogs; metabolic inhibition caused by global cardiac ischemia in swine; and the hypermetabolic syndrome of porcine malignant hyperthermia (MH). Both pacing- and ischemia-induced fatigue resulted in reduction of SR Ca-transport ATPase activity: from 275 +/- 58 to 159 +/- 57 nmol.min-1.mg-1 (mU/mg) and from 577 +/- 82 to 177 +/- 133 mU/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95 +/- 2.4 to 3.11 +/- 0.67 nM/s at 300 nM Ca and 38.7 +/- 10.5 to 16.3 +/- 8.0 nM/s at 1500 nM Ca, respectively (all p less than 0.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r = 0.76; p less than 0.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Pathology Department, Ontario Veterinary College, University of Guelph, Ont., Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Brien
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: J
authors.initials: J
authors.lastname: Weiler
authors.forename: C D
authors.initials: CD
authors.lastname: Ianuzzo
authors.forename: C
authors.initials: C
authors.lastname: Wittnich
authors.forename: G W
authors.initials: GW
authors.lastname: Moe
authors.forename: P W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000503:physiopathology; D004285:Dogs; D004452:Echocardiography; D004558:Electric Stimulation; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008305:Malignant Hyperthermia / Q000503:physiopathology; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009132:Muscles / Q000502:physiology / Q000503:physiopathology* / Q000648:ultrastructure; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
chemical_list: D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D002118:Calcium