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Isoflurane prevents acute lung injury through ADP-mediated platelet inhibition. Surgery 2012 Aug;152(2):270-6

Date

07/26/2012

Pubmed ID

22828148

Pubmed Central ID

PMC3419262

DOI

10.1016/j.surg.2012.05.002

Scopus ID

2-s2.0-84864251334 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

BACKGROUND: Growing evidence suggests platelets are essential in posttraumatic, acute lung injury (ALI). Halogenated ethers interfere with the formation of platelet-granulocyte aggregates. The potential benefit of halogenated ethers has not been investigated in models of trauma/hemorrhagic shock (T/HS). Therefore, we hypothesized that isoflurane decreases T/HS-mediated ALI through platelet inhibition.

METHODS: Sprague-Dawley rats (n = 47) were anesthetized by either pentobarbital or inhaled isoflurane and placed into (1) control, (2) trauma (laparotomy) sham shock, (3) T/HS (mean arterial pressure, 30 mmHg × 45 min), (4) pretreatment with an ADP receptor antagonist, or (5) T/HS with isoflurane initiated during resuscitation groups. ALI was determined by protein and pulmonary immunofluorescence bronchoalveolar lavage (BAL) fluid. Platelet Mapping specifically evaluated thrombin-independent inhibition of the ADP and AA pathways of platelet activation.

RESULTS: Pretreatment with isoflurane abrogated ALI as measured by both BAL fluid protein and pulmonary immunofluorescence (P < .001). Platelet Mapping revealed specific inhibition of the platelet ADP-pathway with isoflurane (P < .001). Pretreatment with an ADP receptor antagonist decreased ALI to sham levels, confirming that specific platelet ADP inhibition decreases ALI. Isoflurane initiated during resuscitation also decreased ALI (P < .001).

CONCLUSION: Isoflurane attenuates ALI through an antiplatelet mechanism, in part, through inhibition of the platelet ADP pathway. Isoflurane given postinjury also protects against ALI, and highlights the potential applications of this therapy in various clinical scenarios of ischemia/reperfusion.

Author List

Harr JN, Moore EE, Stringham J, Wohlauer MV, Fragoso M, Jones WL, Gamboni F, Silliman CC, Banerjee A

MESH terms used to index this publication - Major topics in bold

Acute Lung Injury
Anesthetics, Inhalation
Animals
Blood Platelets
Fluorescent Antibody Technique
Isoflurane
Lung
Male
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P2
Receptors, Purinergic P2Y12
Resuscitation
Shock, Hemorrhagic
Ticlopidine