Many pre-clinical or basic research studies require long-term mechanical ventilation of small laboratory animals, which can be challenging without the appropriate ventilator. CWE has a solution, our SAR-1000 Advanced Small Animal Ventilator.
While the principles of positive-pressure ventilation are straightforward, it often proves difficult to maintain small animals, especially mice, for more than a few hours without causing Ventilator Induced Lung Injury (VILI) and a concomitant degradation in physiological status. The comments here provide some guidelines to achieving success in keeping your animal healthy during long sessions on the ventilator. These suggestions are mainly aimed at the mouse, but apply to all small laboratory mammals.
CWE’s SAR-1000 Small Animal Ventilator is specifically designed to support mice and other small animals safely and effectively during both long and short-term surgeries using two key strategies that have been pointed out in recent studies1.
1. Low Tidal Volume (VT) ventilation with periodic SIGH breaths or Recruitment Maneuvers (RM).
2. Positive End Expiratory Pressure (PEEP).
Both of these important techniques are outlined in detail below.
Low VT ventilation involves using a VT of around 8ml/kg, rather than the commonly used 10 -- 12ml/kg. By itself this would lead to eventual respiratory failure from hypoventilation, but when supplemented with periodic sighs, or RMs, atelectasis is avoided and alveolar recruitment occurs. This scheme maintains good gas exchange and does not promote injury. From the literature1,2, the optimum RM frequency is about 12hr-1, or every five minutes, at a Ppaw (Peak airway pressure) of 30cmH2O.
The second key is the use of PEEP. In combination with the above strategy, a PEEP of around 6cmH2O proves optimal in maintaining patency of the lower lobes and avoiding local atelectasis1,3. A diagram showing how to use PEEP with the SAR-1000 ventilator is linked below.
Comments: The 30cmH2O RM pressure is not an arbitrary value and may seem high for a mouse. This has been experimentally determined to increase lung compliance and is believed to either re-open collapsed alveoli, or possibly recruit a secondary population of alveoli that has a critical opening trans-respiratory pressure. In any case, lower Ppaw pressures are not nearly as effective in maintaining good blood gasses while avoiding VILI.
In summary, a strategy of low VT ventilation, periodic large volume RM breaths, and PEEP should help keep your small animals healthy during ventilation. The Respiratory Rate (RR) should be set appropriately to provide a normal Minute Ventilation (MV) taking into consideration the reduced VT plus the periodic high VT RM breaths. There is much more to this story, including the role of inflammation or pathological changes to lung mechanics, etc. Although positive pressure ventilation is an inherently unnatural operation, much can be learned by studying the patterns of spontaneously breathing animals. For example, the five minute RM interval discussed above could be randomized to better mimic natural patterns and produce even better results2.
CWE Inc.’s SAR-1000 ventilator supports the ventilation strategies discussed above with its built in auto-SIGH function and easy PEEP connection, plus remote control and other capabilities included with the SAR-Comm Software. The SAR-1000 allows you to safely and easily lengthen your surgeries to produce better results and healthier outcomes.
More information can be found here
References (see links below):
1. Lucy Kathleen Reiss, Anke Kowallik, Stefan Uhlig. (2011) Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice
2. W. Alan C. Mutch, Stefan Harms, et.al. (1999) Biologically Variable or Naturally Noisy Mechanical Ventilation Recruits Atelectatic Lung
3. Lillian Moraes, Cíntia Lourenco Santos, Raquel Souza Santos, et.al. (2014) Effects of sigh during pressure control and pressure support ventilation in pulmonary and extrapulmonary mild acute lung injury.