Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

Abstract

BackgroundThere is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI).MethodsSixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations.ResultsHPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001).ConclusionsIn our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

Metformin attenuates ventilator-induced lung injury

“…Indeed, we observed an increase in the tidal volume in lungs ventilated at the higher peak inspiratory pressure/higher tidal volume (HiP groups) during the early phases of injurious ventilation, which (given the applied PCV mode of ventilation) could be translated into an increase in compliance (Figure 3). This increase in compliance after the initiation of high pressure ventilation is a consistent finding in our ex-vivo experiments [5,20,21]. On the other hand, as depicted in Figure 3, during the last 20 minutes of the injurious ventilation, lungs in the HiP-C, but not the HiP-Met group, sustained a decrease in tidal volume (and thus, in compliance).…”

“…The left lung was fixed for histology and a composite histological score was determined as previously described [5,20,21]. …”

Permissive hypercapnia

“…Studies using clinically more relevant (V t ) have further underlined the potential for hypercapnia to protect against mechanical stretch [46][47][48][49]. Studies using clinically more relevant (V t ) have further underlined the potential for hypercapnia to protect against mechanical stretch [46][47][48][49].…”

Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation*

“…Pulmonary vascular dysfunction is a known feature of ARDS/ALI. Pulmonary vascular resistance and pulmonary arterial pressure are elevated in patients with ARDS (4) and in animal models of ALI induced by sepsis/endotoxin (5,6) or HVt ventilation (7). Another key feature of ARDS/ ALI is the mismatch of ventilation and perfusion leading to Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation* intrapulmonary shunting due to an impaired hypoxic pulmonary vasoconstriction (HPV) (8), which contributes to the systemic hypoxemia in ARDS/ALI (9,10).…”