Rationale: Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. Objectives: The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Methods: Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (K fc ), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. Results: In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in K fc . However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of K fc . Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. Conclusions: We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.Keywords: acid aspiration syndrome; extravascular lung water; filtration coefficient; leukocyte count; lung blood contentThe aspiration of gastric acid, which is prone to occur in conditions such as drug overdose, stroke, and general anesthesia, is an increasingly important cause of acute lung injury (ALI), which is associated with high rates of morbidity and mortality (1). In animal models of acid-induced ALI, intratracheal acid instillation induces lung leukocyte sequestration that characteristically precedes pulmonary edema (2, 3). Accordingly, proposed therapeutic strategies include protocols that either inhibit lung leukocyte accumulation (4-8) or reduce alveolar liquid accumulation (9-11). However, strategies for lung endothelial barrier strengthening remain inadequately considered. The lung endothelial barrier, which is established by intercellular junctional proteins of endothelial cells lining lung microvessels, protects against excessive lung liquid accumulation. Decreased lung endothelial barrier function increases transmicrovascular liquid flux, thereby promoting pulmonary edema, which is a hallmark of ALI. Although it has long been known that airway acid instillation injures the lung microvascular barrier (12), relevant therapeutic strategies are not known. This article considers the possibility that...

Most cells possess mechanisms that are able to detect cellular volume shifts and to signal the initiation of appropriate volume regulatory responses. However, the identity and characteristics of the detecting mechanism remain obscure. In this study, we explored the influence of hypertonic and hypotonic challenges of varying magnitude on the characteristics of the ensuing regulatory volume increase (RVI) and regulatory volume decrease (RVD) of cultured bovine corneal endothelial cells (CBCECs). The main question we asked was whether a threshold of stimulation existed that would unleash a regulatory response. CBCECs (passage 1-3) were seeded on rectangular glass coverslips and grown for 1-2 days. We used a procedure based on detection of light scattering to monitor the transient volume changes of such plated cells when subjected to osmotic challenge. The osmometric responses were asymmetric: cells shrank faster than they swelled (by a factor of 3). Complete volume regulatory responses took 10-12 min. Bumetanide (50 microM) resulted in incomplete (50%) RVI. We found no threshold as the cells examined responded to hypertonic and hypotonic stimuli as low as 1%. There was some gradation as stimuli of <4% resulted in incomplete volume regulation. The degree of activation of the volume responses grew as an exponential buildup with the strength of the anisotonic challenge. We discuss how our observations are consistent with volume sensing mechanisms based on both ionic strength and the cytoskeleton.