Mechanisms underlying induced autoresuscitation failure in BALB/c and SWR mice

Abstract

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)

Impaired Cardiorespiratory Recovery after Laryngeal Stimulation in Nicotine-Exposed Young Lambs

“…N lambs had more sighs, and these efforts appeared less efficient in restoring a sustained rise in HR and regular breathing. Sighing and gasping are considered to be key elements in successful cardiorespiratory recovery (27), and our findings of less-efficient sighs support other reports that nicotine exposure impairs the ability to autoresuscitate in situations such as repeated hypoxic exposures or LCR-induced apnea after IL-1B pretreatment (15,28,29).…”

Inhibitory effects of hyperthermia on mechanisms involved in autoresuscitation from hypoxic apnea in mice: a model for thermal stress causing SIDS

“…Four target temperatures were studied: 40.5, 41.5, 42.5, and 43.5°C. Immediately after the target temperature was reached, hypoxic apnea was induced by sudden introduction of a 97% N2-3% CO2 gas mixture into the chamber at the same flow rate (9,10,14). Then a flow of 21% O2 (balance N2) was started at the onset of the apnea to allow for successful AR (10).…”

“…In groups 1 and 2 once gasping ceased and eupneic respiration started, apnea was induced again before the animal was fully awake. This process was repeated until the animal failed to AR (10). Thus the survival rate (% successful AR) after the first episode and total number of successful ARs per animal were determined.…”

“…As used in prior studies, the point at which heart rate increased to 60% of the baseline (averaged over 2 s) was used as an end point for some of the analyses (9,10).…”

“…In contrast, Swiss Webster mice (21-23 days old) have been shown to be prone to AR failure during a relatively narrow window of development and after the first exposure to hypoxia, providing a model more closely resembling the AR failure occurring in SIDS (4,10,14,15). In the present study, we tested four hypotheses in 21-to 23-day-old C57BL/6 mice, which are normally competent in AR.…”