Quantal breathing frequency variation in halothane anaesthetised neonatal rats
Introduction
In 1995, Goodman described quantal patterns of breathing frequency variation in adults during spontaneously breathing propofol anaesthesia (Goodman, 1995). Subsequently we have shown that the described quantal variations are attributable to a form of cardio-respiratory interaction, which has been called cardioventilatory coupling or synchronisation. Cardioventilatory synchronisation is a triggering of inspiratory onset by a cardiovascular afferent associated with a preceding heart beat (Galletly and Larsen, 1997, Galletly and Larsen, 2001, Larsen et al., 1999a, Larsen et al., 1999b). Synchronisation occurs in a range of mammalian species, during anaesthesia, sedation, and in the awake resting state (Larsen and Galletly, 1999, Tzeng et al., 2003). Although the pathway by which the triggering effect of synchronisation is achieved is not known, synchronisation results in several forms of quantal breathing frequency variability (Galletly and Larsen, 1999). The simplest quantal change in ventilatory period occurs when the entrainment ratio between heart beats and breaths changes that is when consecutive breaths are triggered after different numbers of heart beats. Other synchronisation-related quantal variations in breathing frequency occur when the ratio of heart rate to breathing frequency falls within certain regions (known as Arnold tongues) and breath-to-breath changes occur in synchronisation interval (the interval between the inspiratory onset and the triggering cardiac beat). Cardioventilatory synchronisation is a major cause of breath-to-breath breathing rate irregularity during spontaneous breathing anaesthesia in humans (Galletly and Larsen, 1999).
In a recent paper, Mellen et al. (2003) observed that following administration of opiods to awake neonatal rats, respiratory period jumped to integer multiples of the control respiratory period, which they referred to as “quantal slowing”. The authors suggested that this quantal variation may be due to noisy coupling between two brainstem oscillators, or alternatively to a random failure in transmission of respiratory drive. In contrast to the quantal fluctuations that we have previously observed during cardioventilatory synchronisation (in which breath-to-breath respiratory intervals fluctuate in increments of the heart period), the quantal variations observed by Mellen et al. were in multiples of the respiratory period itself; that is, one or more breaths failed to be initiated.
In this study we examined the presence of cardioventilatory synchronisation in neonatal rats (aged 2–14 days), and sought to identify whether this was associated with quantal (respiratory period multiples) fluctuations in respiratory period.
Section snippets
Animals and data acquisition
After gaining ethics approval we studied 26 Wistar rats, two at each day of age from 2- to 14-days old. Anaesthesia was induced by inhalation of 1.5% halothane in oxygen, and was maintained by inhalation of 1% halothane in oxygen via facemask. All preparations were maintained at 37 °C. Using subcutaneous needle electrodes an ECG with large positive R wave signal was obtained. Respiratory activity was recorded by placing a saline-filled PE 50 cannula connected to a pressure transducer into the
Results
Cardioventilatory synchronisation apparent as horizontal banding within the RI interval plot was observed in 24 of 26 rat pups (an example is shown in Fig. 1). In general, synchronisation was seen intermittently, for periods of 30–60 s at a time, rather than consistently over the 5 min data period (Fig. 1), and both patterns I and IV synchronisation were observed. We did not observe any periods of pattern II synchronisation, and therefore there were no examples of quantal respiratory variability
Discussion
In this study we have observed the presence of cardioventilatory synchronisation in rats from 2 to 14 days of age. In addition we observed quantal variation of respiratory frequency associated with one or more missed breaths. This quantal variation was seen most frequently rats less than 12-days old. This form of quantal variation was not related to cardiac influences on inspiratory timing as occurs with quantal variation in respiratory frequency associated with cardioventilatory
References (19)
- et al.
Cardioventilatory synchronisation during anaesthesia
Br. J. Anaesth.
(1997) - et al.
Ventilatory frequency variability during spontaneously breathing anaesthesia
Br. J. Anaesth.
(1999) - et al.
Inspiratory timing during anaesthesia: a model of cardioventilatory synchronisation
Br. J. Anaesth.
(2001) Bimodality of expiratory time in patients anaesthetised with propofol
Br. J. Anaesth.
(1995)- et al.
Cardioventilatory synchronisation: the effect of IPPV
Br. J. Anaesth.
(1999) - et al.
Cardioventilatory synchronisation in atrial fibrillation
Br. J. Anaesth.
(1999) - et al.
Opioid-induced quantal slowing reveals dual networks for respiratory rhythm generation
Neuron
(2003) - et al.
Cardio-respiratory synchronisms: synchrony with artificial circulation
Res. Exp. Med.
(1977) Peripheral Arterial Chemoreceptors and Respiratory–Cardiovascular Interaction
(1997)