Abstract
Background. Hypertonic saline (HTS) resuscitation, in addition to enhancing hemodynamic recovery,
modulates postinjury hyperinflammation in the critically injured. The polymorphonuclear
neutrophil (PMN) cytotoxic response, a key element in the pathogenesis of postinjury
organ dysfunction, is attenuated under hypertonic conditions. Although plasma Na+ rises to 180 mmol/L after HTS infusion, baseline levels are reestablished within
24 hours. We hypothesized that HTS attenuation of the PMN cytotoxic response (β2-integrin expression, elastase release, and O2— production) is reversed upon return to normotonicity, but can be reestablished by
repeated HTS challenge. Methods. Isolated human PMNs were incubated in HTS (Na+ = 180 mmol/L) for 5 minutes at 37°C then returned to normotonicity by centrifugation
and resuspension in isotonic buffer. Stimulated (PAF) β2-integrin expression was measured by flow cytometry. Stimulated (PAF/fMLP) elastase
release and O2— production were measured by cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide
and reduction of cytochrome c (Cyt c). Protein tyrosine phosphorylation in PMN cell
lysates was assessed by Western blot. Results. Clinically relevant levels of HTS induced tyrosine phosphorylation in resting PMNs
and attenuated cytotoxic responses. Reestablishment of normotonicity returned these
functions to baseline. A repeated HTS challenge after restoration of normotonicity
also induced tyrosine phosphorylation and suppressed the cytotoxic response. Conclusions. HTS attenuation of the PMN cytotoxic response is reversible but can be reestablished
by repeated HTS treatment. This phenomenon may provide the unique opportunity to selectively
and temporarily decrease the postinjury inflammatory response when patients are at
greatest risk for PMN-mediated tissue damage. (Surgery 2001;129:567-75.)
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Article info
Publication history
Accepted:
November 24,
2000
Footnotes
*Supported in part by National Institutes of Health grants P50GM4922 and T32GM08315.
**Reprint requests: Ernest E. Moore, MD, Chief, Department of Surgery, Denver Health Medical Center, 777 Bannock St, Denver, CO 80204.
*Surgery 2001;129:567-75.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
