Friday, June 22, 2018


When working with obese mice, what weight should be used when performing flexiVent measurements?

This question is quite an important one for two reasons. First, there is a substantial difference in weight between the obese subjects vs. the lean control group. For instance, obese mice can weigh 50g or more, while their age-matched control group can typically weigh 30g. While there is this significant difference in the weight between both groups, there may not be a large difference in the actual size of the subjects’ lungs.

Second, when working with the flexiVent system, the body weight of the subject is used to scale the amplitude of volume-controlled ventilation patterns and perturbations, such as the Snapshot-150 or the Quick Prime-3. In obese animals, the increase in body weight is not proportional to the subject’s lung size, so sending in a larger volume can have adverse effects on the subject’s lungs.

A recent study performed by Dr. Guivarchis et al.1, highlights the harmful effects of ventilating obese subjects with a tidal volume based on actual weight vs ideal weight using the flexiVent system. In this study, the effects of two hours of mechanical ventilation in a diet-induced obese mice model, with tidal volume calculated on either the actual body weight or the ideal body weight (based on the mean weight of control mice) were demonstrated. Their findings indicate that in comparison to lean control subjects, mechanically ventilating obese subjects with a tidal volume based on actual body weight is harmful.

They observed a noticeable variation in lung mechanics and associated lung inflammation in obese mice ventilated with a tidal volume based on actual body weight. In contrast, obese mice ventilated with a tidal volume calculated using the ideal body weight had lung mechanics and inflammation parameters close to the lean control group.

Therefore, when studies involve the assessment of obese mice, SCIREQ recommends entering the average weight of the lean control group rather than using the actual weight of the obese subjects.

1Guivarch et al. Pulmonary Effects of Adjusting Tidal Volume to Actual or Ideal Body Weight in Ventilated Obese Mice. Sci Rep. 2018 Apr 24;8(1):6439. doi: 10.1038/s41598-018-24615-5.

Monday, June 11, 2018

To open or close the lungs – that is the question!

Although often necessary, mechanical ventilation of small animals during pulmonary measurements can lead to both acute and chronic damage to their lungs, also known as ventilator-induced lung injury (VILI). The injury happens as a result of the frequent opening and closing of alveolar air sacs. Nevertheless, the two most common, and greatly contrasting methods, to study respiratory diseases include open lung- and closed lung-approaches. This has led to many pulmonary researchers conducting experiments with the goal of determining which approach is the least harmful and the best possible way to minimize VILI.


Open-chest models are often used to study ARDS and acute myocardial ischemia and reperfusion. These models allow for investigating cardiac physiology, morphological changes of the lungs, as well as the evaluation of therapeutic interventions. This procedure allows for invasive lung function measurements and tissue harvesting for further experimentation, but must be performed under deep anesthesia. Since opening the chest causes the lungs to collapse, the animals must be mechanically ventilated throughout the process.

The flexiVent has often been used in open-chest experiments, as the system allows for ventilation of the subject with a user-defined positive end-expiratory pressure (PEEP), which can be set to prevent airway collapse. Further, it can facilitate the complete recruitment of the lungs, using the Deep Inflation perturbation, before measurements can be taken.


Recent experimental evidence suggests that high PEEP does not necessarily reduce lung injury but instead, may lead to the contrary. Higher PEEP results in overstretching the alveolar sacs and potential development of edema, among other cardiopulmonary impairment. Moreover, a recent article by Dr. Patricia Rocco and team1, points out that most publications comparing high PEEP with no PEEP, do so with a combination of low tidal volume and high tidal volume, respectively. Thus, there is no clear indication as to what exactly led to the observed outcomes – high PEEP or low tidal volume.

Dr. Rocco goes on to recommend “in order to minimize VILI, we should consider moving away from the classical concept of ‘open up the lungs and keep them open’ towards ‘close down the lungs and keep them closed’”. Fortunately, the flexiVent can be adapted to different experimental conditions, and can provide detailed pulmonary measurements even as research trends change.

1Pelosi, P. et al. 2018. Close down the lungs and keep them resting to minimize ventilator-induced lung injury. Critical Care 22 (1):72.