Macrophage cyclooxygenase expression, immunosuppression, and cardiopulmonary dysfunction after blunt chest trauma.

Background: Two series of experiments were performed in swine who received severe blunt chest trauma. The goals were to determine the time course of constitutive and inducible cyclooxygenase (COX) isozyme expression in pulmonary macrophages (Mphis), and to determine whether COX expression and cardiopulmonary dysfunction were altered when neutrophils (PMNs) were pharmacologically depleted with cyclophosphamide (CYC).

Methods: In series 1 (n = 17), anesthetized, mechanically ventilated swine were subjected to right chest trauma via captive bolt gun, hemorrhage, and a 60-minute shock period.

Combination therapy that targets secondary pulmonary changes after abdominal trauma.

After abdominal trauma, the lung is susceptible to secondary injury caused by acute neutrophil (PMN) sequestration and alveolar capillary membrane disruption. Adenosine is an endogenous anti-inflammatory metabolite that decreases PMN activation. AICAR ([5-amino-1-[beta-D-ribofuranosyl]imidazole-4-carboxamide]riboside) is the prototype of a novel class of anti-inflammatory drugs that increase endogenous adenosine.

Endogenous adenosine and secondary injury after chest trauma.

Background: No previous studies have examined actions of adenosine or related compounds after blunt chest trauma, but we have shown that the prototype adenosine-regulating agent, acadesine (aminoimidazole carboxamide ribonucleotide [AICAR]), has multiple favorable anti-inflammatory actions after other forms of trauma, ischemia, hemorrhage, and sepsis; and that a progressive inflammatory response in the contralateral (uninjured) lung after unilateral blunt chest trauma is caused (in part) by activation and sequestration of circulating leukocytes (white blood cells [WBCs]). Thus, we hypothesized that AICAR would ameliorate WBC-dependent, secondary pathophysiologic changes after blunt chest trauma.

Methods: Mongrel pigs (28+/-1 kg, n = 21) were anesthetized, mechanically ventilated, and injured on the right chest (pulmonary contusion) with a captive bolt gun.

Granulocyte colony-stimulating factor and neutrophil-related changes in local host defense during recovery from shock and intra-abdominal sepsis.

Background: We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum.

Methods: Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma).

Acadesine during fluid resuscitation from shock and abdominal sepsis.

Objective: To determine properties of acadesine, the prototype adenosine regulating agent, in an experimental model in which abdominal sepsis is superimposed onto hemorrhagic shock.

Design: Randomized, blinded animal study.

Setting: University-based animal research facility.