NEUTROPHIL RHEOLOGIC CHANGES IN SEPTIC SHOCK

Decreases in effective capillary brood flow during septic shock may be related to changes in neutrophil rheology which contribute to microva scular exclusion. The purpose of this study was to examine neutrophil deformability, adherence, and aggregation in patients with severe seps is and septic shock. Neutrophils were isolated from six patients with septic shack (SS), 12 patients with severe sepsis (S), six noninfected critically ill patients (CINS), and nine normal volunteers (N). Neutr ophil deformability was determined by examining filtration through 5-m u m filters. Neutrophil aggregation was measured by aggregometry and l eukergy. Neutrophil adherence was examined by assessing the binding of latex beads to neutrophils. Patients with S and SS demonstrated decre ased neutrophil filterability of 27 +/- 2% and 16 +/- 5%, respectively (p < 0.01), in comparison with N subjects, 55 +/- 4% and CINS patient s, 58 +/- 2%. Preincubation of neutrophils from S and SS patients with cytochalasin D significantly increased the percent filtration of neut rophils. Neutrophil aggregation, measured by aggregometry, was increas ed in SS patients, 16 +/- 4% (p < 0.01) compared with N subjects, 1 +/ - 0.2% and CINS patients, 1 +/- 0.2%. Incubation of neutrophils of SS patients with anti-CD11/CD18 significantly increased the filtration of isolated neutrophils to 46 +/- 3% (p < 0.01) and decreased aggregatio n to 7 +/- 2% . Neutrophil adherence was not increased in S or SS pati ents. These observations suggest that neutrophil deformability is decr eased in patients with S and SS. Increased leukoaggregation may also c ontribute to decreased filterability of neutrophils in SS patients. Th ese mechanisms may play a role in impaired microvascular flow in septi c shock.