Heritable differences in respiratory drive and breathing pattern in mice during anaesthesia and emergence †

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Abstract
Postanaesthetic hypoxia and ischaemia can lead to postoperative morbidity and mortality. We studied the effect of isoflurane anaesthesia in two inbred mouse strains known for phenotypic differences in breathing pattern and respiratory drive during carbon dioxide challenge and their first-generation offspring (F(1)). Using whole body plethysmography, we assessed respiratory rate (RR) and pressure amplitude (Amp) in male B6 (high responder to hypercapnia), C3 (low responder), and F(1) mice at rest, during anaesthesia with isoflurane, and during recovery from anaesthesia. At each time point, the magnitude and pattern of breathing were determined during hypercapnic challenge (FI(CO(2)) = 0.08). Data (mean (SD)) were analysed by generalized ANOVA with post hoc Bonferroni's correction (P<0.05). During isoflurane anaesthesia, strain differences between B6 and C3 mice in RR were obscured while differences in Amp persisted. In contrast to baseline RR responses to carbon dioxide were significantly reduced at 0.5 MAC (increase in RR: 175 (33) bpm, 147 (44) bpm, 127 (33) bpm, for B6, C3, and F(1) strains respectively) and completely blocked at 1.5 MAC (change in RR: -3 (10) bpm, -2 (1) bpm, -4 (5) bpm, for B6, C3, and F(1) strains, respectively). During recovery, B6 mice showed a significant increase in RR (77 (33) bpm; P<0.0001) as well as in Amp. This was not observed in either C3 (-22 (31) bpm) or F(1) mice (23 (51) bpm). Isoflurane anaesthesia abolished the strain differences in respiratory drive between B6, C3, and F(1) mice. However, during recovery from anaesthesia, significant strain variation in respiratory drive reappeared and was more pronounced compared with pre-anaesthetic levels. These results suggested, that genetic differences may have minimal contribution to decreased respiratory drive during anaesthesia, but may be a major risk factor for post-operative hypoventilation and the associated morbidity and mortality.

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