title: Hypoxia, not hypercapnia, induces cardiorespiratory failure in rats.
abstract: Mechanical respiratory loads induce cardiorespiratory failure, presumably by increasing O2 demand concurrently with decreases in O2 availability (decreased PaO2). We tested the hypothesis that asphyxia alone can cause cardiorespiratory failure ("failure") in pentobarbital-anesthetized rats. We also tested the hypothesis that hypoxia, not hypercapnia, is responsible by supplying supplemental O2 during mechanical loading in a separate group of rats. Asphyxia (mean PaO2 and PaCO2 of 43 and 69mmHg, respectively) resulted in failure, evident as a slowing of mean respiratory frequency (133-83breaths/min) and a sudden and large drop in mean arterial pressure (71-47mmHg), after 214±66min (n=16; range 117-355min). Neither respiratory drive nor heart rate decreased, indicating that failure was peripheral, not central. Of 8 rats tested after 3h of asphyxia for the presence in blood of cardiac troponin T, all were positive. In an additional 6 rats, normocapnic hypoxia (mean PaCO2 and PaO2 were 39±2.2 and 41±3.1mmHg, respectively) caused failure after an average 205min (range 181-275min), no different from that of asphyxic rats. In the 6 rats that breathed O2 during an initially moderate inspiratory resistive load, endurances exceeded 7h (failure occurring only because we increased the load after 6h) and tracheal pressure and left ventricular dP/dt were maintained despite supercarbia (PaCO2>150mmHg). Thus, asphyxia alone can induce failure, the failure is due to hypoxia, not hypercapnia, and hypercapnia has minimal effects on cardiac and respiratory muscle function in the presence of hyperoxia.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6. Electronic address: jeremys@uoguelph.ca.
authors.forename: J A
authors.initials: JA
authors.lastname: Simpson
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: S
authors.initials: S
authors.lastname: Iscoe
mesh_terms: D000758:Anesthesia; D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D001237:Asphyxia / Q000503:physiopathology; D003964:Diaphragm / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate; D006352:Heart Ventricles / Q000503:physiopathology; D006935:Hypercapnia / Q000150:complications / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D010424:Pentobarbital; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000209:etiology / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology; D013997:Time Factors; D014132:Trachea / Q000503:physiopathology; D020107:Troponin T / Q000097:blood
chemical_list: D020107:Troponin T; D010424:Pentobarbital; D010100:Oxygen
keywords: Cardiac troponin; Hypercapnia; Hyperoxia