The effect of maturation and motor activity on recovery from hypoxic apnea by gasping (autoresuscitation) was investigated in Swiss Webster mice and a SW-related strain. Apnea was induced with 97% N2-3% CO2 and air given at its onset. In 69 Swiss Webster-related strain mice that gasped for at least 5s, the survival rates were 100% in 1- to 16-day-old mice, 19% in 17- to 23-day-old mice, and 90% in adults. The rates in 81 Swiss Webster mice were 100, 70, and 95%, respectively. The decrease in survival in 17- to 23-day-old mice was statistically significant for both strains, as was the difference in survival in 17- to 23-day-old mice between the two strains. Gasping was absent or of brief (less than 5s) duration in 15 Swiss Webster mice that failed to recover. Seizure-like activity was observed during hypoxic apnea and gasping but was not seen significantly more often in mice that died. Simultaneous recordings of limb movement (electromyogram) and breathing pattern indicated that movement did not interfere with the occurrence of gasping. We conclude that in adults and very young mice autoresuscitation is a powerful mechanism for recovery from hypoxia, but at an intermediate age, it is frequently unsuccessful.

Mechanisms underlying failure of autoresuscitation from hypoxic apnea were investigated. Failure was induced by repeated exposure to hypoxia. The influence of maturation was studied in adults, weanlings, and 10- and 5-day-old mice. Mice successful at autoresuscitation (BALB/c) as well as those prone to autoresuscitation failure (SWR weanlings) were studied. Hypoxic apnea was induced with 97% N2-3% CO2, and 21% O2 was given at its onset; electrocardiogram and ventilation were recorded. Hypoxic exposure was repeated if autoresuscitation (recovery of eupnea) occurred. Autoresuscitation failure (death) was induced in all mice. Young BALB/c mice tolerated more trials than older mice. SWR weanlings frequently failed to autoresuscitate on the initial exposure and tolerated fewer repeat trials overall than age-matched BALB/c mice. Induced autoresuscitation failure in all mice appeared to be unrelated to gasping regulation, because both gasp number and amplitude were similar during the failed trial and the previous successful trial. In most mice, failure was associated with absent recovery of heart rate during gasping. In BALB/c mice in particular, this persistent bradycardia was usually due to heart block, which occurred in 95% of failed trials. In addition, heart block occurred with increasing frequency on later successful trials, but conversion to sinus rhythm always preceded successful autoresuscitation. Heart block was also frequent in SWR mice and had similar consequences. BALB/c mice exposed to continuous anoxia survived longer than SWR mice, indicating increased endurance of components of the autoresuscitation mechanism not directly related to the ventilatory function of gasping (e.g., cardiovascular components).(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism of failure of autoresuscitation from hypoxic apnea in 17- to 23-day-old (weanling) Swiss Webster related/J mice was investigated by recording electrocardiogram (ECG) and ventilation in adult, weanling, and 11-day-old mice. Hypoxic apnea was induced with 97% N2-3% CO2. O2 (21% or 50% O2) or 97% N2-3% CO2 was given at the onset of apnea. The ECG showed no arrhythmias predictive of failure of autoresuscitation. The first indication of failure was a progressive fall in gasp volume ("run down"). This pattern also occurred in animals given continuous 97% N2-3% CO2 and was significantly different from that in mice that survived. Gasping duration in 97% N2 was longer in weanlings than adults but shorter than in 11 day olds. Respiratory and heart rate recovery were more rapid in adults than in weanlings. Although recovery in high O2 was more rapid, the survival rate was not increased. The lack of effect of high O2 on survival and the virtually identical pattern of gasping in mice dying in 97% N2 and air leads us to conclude that in mice that fail to autoresuscitate little or no O2 reaches the medullary respiratory centers. We speculate that this may be due to increased vulnerability of cardiac muscle to anoxia in 17- to 23-day-old mice, resulting in early and severe heart failure.

ABSTRAm. The maturation of the process of spontaneous recovery from hypoxic apnea by gasping (autoresuscitation) was characterized in adult, weanling (18-22 d), and infant (5 and 10 d) BALB/c mice. ECG and respiration

Rapid steady-state CO2 responses were determined in five normal adults at rest and at up to six levels of exercise by injecting pure CO2 at a constant flow into the inspiratory limb of a breathing circuit. Ventilation (V) was measured with a dry gas meter and PCO2 at the mouth was recorded by a mass spectrometer. Mean alveolar PCO2 (PACO2) was taken as equal to end-tidal PCO2 at rest, and during exercise was derived graphically from the sloping alveolar plateaus. The accuracy of the latter method was checked in separate experiments against arterial PCO2 (PaCO2). The mean results showed a linear relationship between change in PACO2 and change in V for work loads ranging from rest to 75 W (r = 0.94-0.98). Above 75 W the response became concave down with an initial essentially isocapnic phase. This suggests that during exercise there is a large increase in CO2 sensitivity about the control point.