Nebulization of a non-anticoagulant heparinoid (gm1892) attenuates lung lymph flow after acute lung injury in sheep

After acute lung injury transvascular fluid flux increases secondary to an increased microvascular permeability to protein, and is thought to be a consequence of an inflammatory process. This manifestation has been well documented in an ovine model in which acute lung injury is induced by smoke inhalation. Kimura et. al showed that heparin nebulization would decrease lung lymph flow. GM-1892 is a low molecular weight heparin analog that has no anticoagulation properties. We hypothesized that this heparin analog would reduce transvascular fluid flux in our ovine model. Sheep (n=12)'were surgically prepared for chronic study by placement of cardiopulmonary catheters and a lung lymph fistula. After a 5 day recovery, baseline data were collected and the sheep insufflated with cotton smoke. They were then randomized into two erouos. a control eroun (3 ml lactated rineers. n-fi} and GM-1892 (2mg/kg,n=6).The solutions were delivered via an in line nebulizing system 1 hr after injury and each subsequent 4 hrs for the duration of the study (48hrs). The GM-1892 attenuated the increase in lymph flow when compared to the control group. P<0.05, vs baseline, (†) between groups. This confirmed our hypothesis. Reference: Circ Shock, 25:333,1988. Supported by NIH GM33324 and the Shriners of NA.