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Because expiratory threshold loads increase intrathoracic pressure and decrease left ventricular afterload, we hypothesized that anesthetized rats forced to breathe against such a load would experience only diaphragmatic failure. Loading approximately doubled end-expiratory lung volume, halved respiratory frequency, and caused arterial hypoxemia and hypercapnia, respiratory acidosis, and increased inspiratory drive. Although hyperinflation immediately reduced the diaphragm's mechanical advantage, fatigue did not occur until near load termination. Mean arterial pressure progressively fell, becoming significant (cardiovascular failure) midway through loading despite tachycardia. Loading was terminated (endurance 125 \u00b1 43 min; range 82\u2013206 min) when mean arterial pressure dropped below 50 mmHg. Blood samples taken immediately after load termination revealed hypoglycemia, hyperkalemia, and cardiac troponin T, the last indicating myocardial injury that was, according to histology, mainly in the right ventricle. This damage probably reflects a combination of decreased O<jats:sub>2<\/jats:sub>delivery (decreased venous return and arterial hypoxemia) and greater afterload due to hyperinflation-induced increase in pulmonary vascular resistance. Thus, in rats breathing at an increased end-expiratory lung volume, cardiorespiratory, not just respiratory, failure still occurred. Right heart injury and dysfunction may contribute to the increased morbidity and mortality associated with acute exacerbations of obstructive airway disease.<\/jats:p>","DOI":"10.1152\/japplphysiol.91342.2008","type":"journal-article","created":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T02:08:55Z","timestamp":1241143735000},"page":"275-282","source":"Crossref","is-referenced-by-count":9,"title":["Hyperinflation-induced cardiorespiratory failure in rats"],"prefix":"10.1152","volume":"107","author":[{"given":"Jeremy A.","family":"Simpson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith R.","family":"Brunt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine P.","family":"Collier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Iscoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1985.59.5.1527"},{"key":"R2","unstructured":"Amorim S, Dias P, Rodrigues RA, Araujo V, Macedo F, Maciel MJ, Goncalves FR.Troponin I as a marker of right ventricular dysfunction and severity of pulmonary embolism.Rev Port Cardiol25: 181\u2013186, 2006."},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2006.10.038"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1978.45.3.425"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-003-1635-0"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Barbera JA, Roca J, Ferrer A, Felez MA, Diaz O, Roger N, Rodriguez-Roisin R.Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease.Eur Respir J10: 1285\u20131291, 1998.","DOI":"10.1183\/09031936.97.10061285"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.66.5.2305"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91472.2008"},{"key":"R9","unstructured":"Drislane FW, Samuels MA, Kozakewich H, Schoen FJ, Strunk RC.Myocardial contraction band lesions in patients with fatal asthma: possible neurocardiologic mechanisms.Am Rev Respir Dis135: 498\u2013501, 1987."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/141.4_Pt_1.926"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(80)90049-3"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1982.53.5.1110"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-6723.2004.00589.x"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1097\/00003643-200308000-00003"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1981.51.4.1009"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00046-X"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.77.5.2440"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1186\/cc3057"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1378\/chest.110.1.189"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.4.1563"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-006-0482-1"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1985.59.1.113"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2005.08.029"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.3109\/10520299709082237"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.73.5.1888"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.2170\/jjphysiol.42.779"},{"key":"R27","unstructured":"Parker CM, O'Donnell DE.Pathophysiology of acute exacerbations of COPD. 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