Abstract
BACKGROUND: Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH(2)O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). METHODS: Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H(DS), n = 6) and (2) over-distension + low dynamic strain (OD + L(DS), n = 6). OD was caused by setting the inspiratory pressure at 40 cmH(2)O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. RESULTS: In normal tissue (N(T)), OD + L(DS) caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H(DS). In acutely injured tissue (ALI(T)), OD + L(DS) resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H(DS). CONCLUSIONS: Both N(T) and ALI(T) are resistant to VILI caused by OD alone, but when combined with a H(DS), significant tissue injury develops.