Effects of Similar Mechanical Power Resulting From Different Combinations of Respiratory Variables on Lung Damage in Experimental Acute Respiratory Distress Syndrome

Objectives: Mechanical power is a crucial concept in understanding ventilator-induced lung injury (VILI). We adopted the null hypothesis that under the same mechanical power, resulting from combinations of different static and dynamic variables—some with high stress per cycle and others without—would inflict similar degrees of damage on lung epithelial and endothelial cells as well as on the extracellular matrix in experimental acute respiratory distress syndrome (ARDS). To test this hypothesis, we varied tidal volume (V t ), which correlates with the stretching force per cycle, while adjusting respiratory rate (RR) to yield similar mechanical power values for identical durations across all experimental groups. Design: Animal study. Setting: Laboratory investigation. Subjects: Thirty male Wistar rats (333 ± 26 g). Interventions: Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, animals were anesthetized and mechanically ventilated (positive end-expiratory pressure = 3 cm H 2 O) with combination of V t and RR sufficient to induce similar mechanical power ( n = 8/group): V t = 6 mL/kg, RR = 140 breaths/minute (low V t –high RR [LVT–HRR]); V t = 12 mL/kg, RR = 70 breaths/minute (high V t –low RR [HVT–LRR]); and V t = 18 mL/kg, RR = 50 breaths/minute (very-high V t –very-low RR [VHVT–VLRR]). All groups were ventilated for 80 minutes. A control group, not subjected to mechanical ventilation (MV), was used for molecular biology analyses. Measurements and Main Results: After 80 minutes of MV, lung overdistension, alveolar/interstitial edema, fractional area of E-cadherin, and biomarkers of lung inflammation (interleukin-6), lung stretch (amphiregulin), damage to epithelial (surfactant protein B) and endothelial cells (vascular cell adhesion molecule 1 and angiopoietin-2), and extracellular matrix (versican and syndecan) were higher in group VHVT–VLRR than LVT–HRR. Plateau pressure and driving pressure increased progressively from LVT–HRR to HVT–LRR and VHVT–VLRR. Conclusions: In the current experimental model of ARDS, mechanical power alone is insufficient to account for VILI. Instead, the manner in which its components are applied determines the extent of injury at a given mechanical power value.