Hypoxia, not hypercapnia, induces cardiorespiratory failure in rats

• Asphyxia alone can induce cardiorespiratory failure.
• This failure is peripheral (heart and respiratory muscles), and is due to hypoxemia, not hypercapnia.
• Provision of supplementary oxygen prolongs endurance remarkably and, despite extraordinarily high levels of arterial PCO2, left ventricular contractility is not impaired.
• Concerns about the dangers of hypercarbia during treatment of respiratory failure with supplementary oxygen may be exaggerated.

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 69 mmHg, respectively) resulted in failure, evident as a slowing of mean respiratory frequency (133–83 breaths/min) and a sudden and large drop in mean arterial pressure (71–47 mmHg), after 214 ± 66 min (n = 16; range 117–355 min). Neither respiratory drive nor heart rate decreased, indicating that failure was peripheral, not central. Of 8 rats tested after 3 h 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 ± 3.1 mmHg, respectively) caused failure after an average 205 min (range 181–275 min), no different from that of asphyxic rats. In the 6 rats that breathed O2 during an initially moderate inspiratory resistive load, endurances exceeded 7 h (failure occurring only because we increased the load after 6 h) and tracheal pressure and left ventricular dP/dt were maintained despite supercarbia (PaCO2 > 150 mmHg). 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.