Reply to Jha: Addition of 5% CO2 to Inspiratory Gas in Preventing Lung Injury Due to Pulmonary Artery Ligation.

From the Authors:

We thank Jha for the insightful comments on our recent experimental study (1). Indeed, the experiment offers food for thought as we are at the very beginning of understanding pathophysiological changes induced by unilateral pulmonary artery ligation (UPAL) and mechanisms of lung protection by inhaled 5% CO2.

After UPAL, PaCO did not increase, as if the additional experimental dead space did not affect the efficiency of gas exchange. Several pivotal studies on animals (2) and humans (3, 4) already showed that PaCO does not change after unilateral pulmonary artery occlusion, despite little or no increase in minute ventilation. Our and previous findings suggest that a compensatory mechanism, consisting of redistribution of ventilation toward perfused lung regions, maintains the effectiveness of CO2 clearance, avoiding the increase in wasted ventilation. This might help with understanding the lack of increase in PaCO after UPAL in our experiment. Moreover, decreased total CO2 production might also have occurred along the course of the experiment and affected the level of PaCO at stable minute ventilation independently from changes in dead space. As inhalation of 5% CO2 counteracted the compensatory redistribution of ventilation after UPAL, wasted ventilation could have been higher in the ligation + FiCO (fractional inspired CO2) animals and might have contributed to the higher PaCO in this group.

With respect to the comments on the PaCO–end-tidal CO2 (ETCO) gradient, we would like to underline that the latter might have reflected regional alveolar CO2 rather than the global average level. Indeed, unilateral bronchoconstriction and/or pneumoconstriction might have caused delayed or even incomplete exhalation from the ligated lung, which might have altered ETCO values (4, 5), potentially hindering the reliability of the PaCO–ETCO gradient to estimate wasted ventilation.

We appreciate the thoughtful comments on changes in pulmonary vascular resistance (PVR). As suggested by Jha, the combination of ligation and hypercapnia induced a relevant increase in PVR in the ligation + FiCO group. Nevertheless, this effect tended to be dampened over time, possibly due to renal buffering of respiratory acidosis (6), while the increase in PVR seemed to progress in the ligation group, and we only foresee the development of injury as an underlying mechanism. The effects of inhaled CO2 on PVR and right heart function in the presence of increased dead space definitely need further assessment before envisioning clinical applications (7).

Finally, as suggested by Jha, alternative mechanisms of injury remain to be investigated, including the role of increased blood flow to the right nonligated lung and possible inflammatory cross-talk between the two lungs.