thiobarbituric-acid and Escherichia-coli-Infections

Pentoxifylline (PTXF), a drug demonstrated to improve intermittent claudication, is a methylxanthine that increases intracellular cyclic AMP (cAMP) and, unlike theophylline, has few side effects. Because increased cAMP levels have been associated with a decrease in lung injury, we examined the effects of PTXF on acute lung injury in a septic guinea pig model. Five groups of guinea pigs were studied over a period of 8 h. (Group I: saline control injected intravenously with 2 ml of saline; Group II: septic control injected intravenously with 2 x 10(9) Escherichia coli; Group III: E. coli septicemia plus PTXF bolus 20 mg/kg injected 5 min before E. coli injection; Group IV: E. coli septicemia plus PTXF continuous infusion, begun with bolus [20 mg/kg] followed by continuous infusion [20 mg/kg/h] started 60 min before injection of E. coli; Group V: PTXF continuous infusion [20 mg/kg/h] control). Arterial blood gases, arterial blood pressure, and blood WBC counts were monitored serially for 8 h. Lung water (wet-to-dry ratio), the concentration ratio of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid to that in plasma (albumin index; AI), total cell count in BAL fluid, thiobarbituric-acid-reactive material (TBARM), and the lysosomal enzyme beta-glucuronidase (beta-G) were examined. Lung tissue was studied histologically to assess neutrophil accumulation. Our results showed that E. coli septicemia caused significant peripheral neutropenia and histopathologic evidence of neutrophil alveolitis associated with an increased ratio of TBARM and beta-G in BAL fluid as compared with those in plasma (TBARM BAL ratio and beta-G BAL ratio).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Bronchoalveolar Lavage Fluid; Escherichia coli Infections; Female; Glucuronidase; Guinea Pigs; Lung; Lung Diseases; Neutrophils; Pentoxifylline; Sepsis; Theobromine; Thiobarbiturates

We developed a new model of acute lung injury caused by live Escherichia coli peritonitis in guinea pigs. Arterial blood gas determinations, arterial blood pressure, and white blood cell counts were monitored serially for 12 h after the injection of either 2 x 10(9) E. coli J96 or saline. Lung water, albumin concentration in bronchoalveolar lavage fluid (BALF) and in lung tissue, WBC counts in BALF, and thiobarbituric-acid-reactive materials (TBARM) in plasma, lung tissue, and BALF were examined. Increased TBARM might be associated with pulmonary injury and are produced either by the generation of lipoperoxides secondary to oxygen-free radicals or as metabolic byproducts of prostanoid metabolism. Lung tissue sections were studied by light microscopy. E. coli peritonitis, as compared with control animals, caused significant peripheral neutropenia, histopathologic evidence of lung inflammation, acidosis, and hypotension. The wet-to-dry lung ratio was increased in the peritonitis group when compared with that in the control group (p less than 0.01). Pulmonary edema in the peritonitis group was associated with significantly increased albumin concentrations in BALF and lung tissue. We report the new finding of increased TBARM concentrations in BALF after E. coli peritonitis (p less than 0.01 and p less than 0.05, respectively). In contrast, plasma TBARM concentrations were unchanged. The levels of TBARM in the BALF correlated significantly with both lung water (p less than 0.01) and lung tissue albumin concentration (p less than 0.01). The measurement of elevated TBARM in BALF may allow acute lung injury to be detected. We conclude that this model may be useful for further studies of acute lung injury caused by E. coli peritonitis.

Topics: Animals; Blood Pressure; Body Water; Bronchoalveolar Lavage Fluid; Escherichia coli Infections; Lung; Organ Size; Osmolar Concentration; Peritonitis; Pulmonary Edema; Serum Albumin; Thiobarbiturates