{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T10:23:16Z","timestamp":1752229396057},"reference-count":0,"publisher":"Canadian Science Publishing","issue":"2","license":[{"start":{"date-parts":[[1991,2,1]],"date-time":"1991-02-01T00:00:00Z","timestamp":665366400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[1991,2,1]]},"abstract":"<jats:p> 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\u2013contraction 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\u2002\u00b1\u200258 to 159\u2002\u00b1\u200257\u2002nmol\u2219min<jats:sup>\u22121<\/jats:sup>\u2219mg<jats:sup>\u22121<\/jats:sup>\u2002(mU\/mg) and from 577\u2002\u00b1\u200282 to 177\u2002\u00b1\u2002133\u2002mU\/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95\u2002\u00b1\u20022.4 to 3.11\u2002\u00b1\u20020.67\u2002nM\/s at 300\u2002nM Ca and 38.7\u2002\u00b1\u200210.5 to 16.3\u2002\u00b1\u20028.0\u2002nM\/s at 1500\u2002nM Ca, respectively (all p\u2002&lt;\u20020.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r\u2002=\u20020.76; p\u2002&lt;\u20020.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration. In the pacing model Ca-ATPase activity and left ventricular diastolic area were correlated (r\u2002=\u2002\u22120.64), in the ischemia model Ca-ATPase activity was highly correlated with myocardial lactate concentration (r\u2002=\u2002\u22120.83) and acidity (r\u2002=\u2002\u22120.85) but not glycogen content, and in the malignant hyperthermia model Ca-sequestration activity was correlated with myocardial ionized Ca concentration (r\u2002=\u2002\u22120.63) (all p\u2002&lt;\u20020.001). We conclude that failure of Ca sequestration by SR plays a major role in the pathogenesis of cardiac and muscle fatigue and failure owing to relative functional overload. A model is presented for the role of the SR in the pathogenesis of striated muscle fatigue.Key words: heart disease, fatigue, sarcoplasmic reticulum, Ca ATPase, Ca channel, malignant hyperthermia. <\/jats:p>","DOI":"10.1139\/y91-040","type":"journal-article","created":{"date-parts":[[2011,4,24]],"date-time":"2011-04-24T08:57:55Z","timestamp":1303635475000},"page":"262-268","source":"Crossref","is-referenced-by-count":8,"title":["Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation\u2013contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure"],"prefix":"10.1139","volume":"69","author":[{"given":"Peter James","family":"O'brien","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. David","family":"Ianuzzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carin","family":"Wittnich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon W.","family":"Moe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/pdf\/10.1139\/y91-040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T15:23:34Z","timestamp":1578237814000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/10.1139\/y91-040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1991,2,1]]}},"alternative-id":["10.1139\/y91-040"],"URL":"https:\/\/doi.org\/10.1139\/y91-040","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"value":"0008-4212","type":"print"},{"value":"1205-7541","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,2,1]]}}}