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Pentoxifylline attenuates pulmonary macromolecular leakage after intestinal ischemia-reperfusion
M B Carter1, M A Wilson, W B Wead
1Department of Surgery, School of Medicine, University of Louisville, Ky, USA.
Objective:
To assess the effects of pentoxifylline posttreatment on hemodynamic variables and acute pulmonary injury in the rat intestinal ischemia-reperfusion (I-R) model, using a recently developed method of fluorescent intravital pulmonary videomicroscopy.
Design:
Anesthetized male Sprague-Dawley rats were cannulated for measurement of mean arterial pressure, heart rate, cardiac output, arterial blood gas values, and hematocrit. Rats underwent isolation of the superior mesenteric artery for intestinal I-R (45 minutes of ischemia, 120 minutes of reperfusion) and right lateral thoracotomy for pulmonary videomicroscopy. Epi-illumination fluorescent videomicroscopy was used to quantitate leakage of intravascular fluorescently labeled albumin into alveoli, while hemodynamic variables were simultaneously recorded. In the treatment groups, pentoxifylline was administered after 30 minutes of intestinal ischemia. Data (mean +/- SEM) were recorded before and during intestinal ischemia and after reperfusion at 30-minute intervals.
Main Outcome Measure:
The appearance of fluorescently labeled albumin into alveolar airspaces was quantitated off-line by computer and reported as the alveolar leak index.
Results:
Intestinal I-R caused alveolar macromolecular leakage, marked by a 300% +/- 48% increase from baseline (P < .05) in the alveolar leak index. Intestinal I-R also produced systemic hemodynamic instability demonstrated by a decrease in the mean arterial blood pressure (-36% +/- 5% vs baseline, P < .05) and cardiac output (-42% +/- 6% vs baseline, P < .05), metabolic acidosis (final arterial pH of 7.17, P < .05 vs initial pH), and a 2.3-fold increase in the intravenous fluid requirement when compared with that in sham animals (P < .05). Treatment with pentoxifylline 30 minutes after intestinal ischemia attenuated pulmonary macromolecular leakage (P < .05 vs nontreated I-R) and reduced the decrease in cardiac output (-15% +/- 7% vs baseline, not statistically significant). Pentoxifylline treatment had no effect on the mean arterial blood pressure, heart rate, metabolic acidosis, or intravenous fluid requirement.
Conclusions:
Pentoxifylline reduces alveolar capillary membrane injury and subsequent protein leakage and improves cardiac output when administered after 30 minutes of intestinal ischemia. These data suggest that pentoxifylline may be a possible candidate as a future therapy for acute pulmonary dysfunction. Further studies in human patients are necessary.
Insights
Pentoxifylline treatment post-intestinal ischemia-reperfusion attenuated pulmonary injury and improved cardiac output in rats. This suggests pentoxifylline may be a potential therapy for acute pulmonary dysfunction.
Area of Science:
- Physiology
- Pharmacology
- Pulmonary Medicine
Background:
- Intestinal ischemia-reperfusion (I-R) can lead to systemic complications, including acute pulmonary injury.
- Assessing the efficacy of therapeutic interventions in mitigating these complications is crucial.
Purpose of the Study:
- To evaluate the effects of pentoxifylline on hemodynamic variables and pulmonary injury following intestinal I-R in a rat model.
- To utilize advanced fluorescent intravital pulmonary videomicroscopy for precise outcome measurement.
Main Methods:
- Male Sprague-Dawley rats underwent intestinal I-R, with hemodynamic parameters and arterial blood gases monitored.
- Pulmonary videomicroscopy quantified alveolar albumin leakage, serving as the primary outcome measure.
- Pentoxifylline was administered post-ischemia, and data were collected before, during, and after reperfusion.
Main Results:
- Intestinal I-R significantly increased alveolar macromolecular leakage and caused hemodynamic instability, including decreased blood pressure and cardiac output.
- Pentoxifylline treatment attenuated pulmonary leakage and mitigated the reduction in cardiac output.
- No significant effects of pentoxifylline were observed on mean arterial blood pressure, heart rate, or metabolic acidosis.
Conclusions:
- Pentoxifylline administration after intestinal ischemia reduces alveolar capillary membrane injury and protein leakage.
- The drug also demonstrates a beneficial effect on cardiac output in this model.
- These findings support pentoxifylline as a potential therapeutic agent for acute pulmonary dysfunction, warranting further clinical investigation.