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Pentoxifylline Markedly Reduces Pulmonary Neutrophil Sequestration* FREE TO VIEW

I. Ehrhart, PhD; L. McCloud; K.M. Creamer, MD; H. Ocasio
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*From the Vascular Biology Center, Medical College of Georgia, Augusta, GA. Supported by the Georgia Affiliate, American Heart Association.

Correspondence to: I. Ehrhart, PhD, Department of Physiology and Endocrinology, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500

Chest. 1999;116(suppl_1):34S. doi:10.1378/chest.116.suppl_1.34S
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The size of the sequestered pulmonary neutrophil (polymorphonuclear leukocyte [PMN]) pool is increased in various types of acute lung injury. Proteases and superoxide radicals released by activated PMNs are putative mediators of lung injury. Pentoxifylline (PTX), a methylxanthine derivative, increases PMN deformability. Since decreased deformability increases leukocyte (WBC) sequestration by the lung, we hypothesized that PTX would reduce pulmonary WBC and PMN sequestration.

Autologous blood was recirculated at constant flow through an isolated canine lung lobe while blood samples were obtained for WBC counts and differential cell counts. Since the perfusion circuit neither takes up nor releases WBCs, change in circulating WBC ([WBC]) or PMN count ([PMN]) is opposite to change in size of the pulmonary sequestered cell pool. PTX (10−3 M) increased [WBC] within 1 min (3.0 ± 0.8 vs 2.1 ± 0.8 × 103 cells per microliter, p < 0.05, n = 6) without altering pulmonary arterial pressure. The increase in [WBC] post-PTX could not be detected as an arterial-venous difference across the lung (p > 0.05). At 90 min post-PTX, [WBC] was increased 85% (3,843 ± 498 vs 2,082 ± 330 WBC per microliter) and [PMN] was increased 147% (1,124 ± 143 vs 455 ± 78 PMN per microliter) over baseline (p < 0.001, n = 14). In the absence of PTX, neither [WBC] nor [PMN] increased (p > 0.05, n = 5). The increase in the [PMN] represents at least a 20-fold greater decrease in the size of the sequestered lung PMN pool since the 500-mL circulating blood volume is > 20 times the lobe blood volume. In contrast, epinephrine, 1 to 2 mg, which increased pulmonary arterial pressure from 16.7 to 29.4 cm H2O (p < 0.05, n = 7), transiently increased [WBC] only 45% (1,604 ± 365 vs 1,104 ± 139 cells per microliter, p < 0.05). Increasing blood flow from 600 to 1,700 mL/min increased [WBC] only 40% (3,166 ± 1,010 vs 2,265 ± 627 cells per microliter, p > 0.05, n = 5). Thus, relative to other interventions, PTX caused an intense and sustained decrease in the sequestered WBC pool. This decrease was associated with a marked mobilization of PMNs from the lung.




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