Journal article
Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline
The Journal of pharmacology and experimental therapeutics, Vol.260(3), pp.1250-1256
03/01/1992
DOI: 10.1016/S0022-3565(25)11436-5
PMID: 1312165
Abstract
Myocardial ischemia and reperfusion cause coronary vascular injury involving both the large epicardial arteries and the microcirculation. Although the mechanisms are unclear, leukocytes appear to play an important role. Since the methylxanthine derivative pentoxifylline (PTX) decreases neutrophil activity in vitro, we hypothesized that it might diminish coronary vascular injury due to ischemia and reperfusion. We investigated the effects of PTX on coronary microvascular and epicardial artery injury in open chest, anesthetized dogs undergoing moderate (60 min) or more prolonged (90 min) ischemia due to left anterior descending coronary artery occlusion followed by 60 min of reperfusion. As an index of microvascular injury, we assessed regional permeability with a dual radioisotope protein leak index (PLI) method. Both ischemic periods with reperfusion increased the PLI of severely ischemic (flow less than or equal to 20/ml/min/100 g) myocardium by 2.5- and 3-fold, respectively, compared to nonischemic (flow greater than or equal to 100 ml/min/100 g) myocardium. Treated dogs received PTX (20 mg/kg bolus plus 0.1 mg/kg/min infusion) before ischemia. PTX reduced the increase in the PLI by 40% after 60 min of ischemia (PLI = 5.87 +/- 0.48 vs. 4.10 +/- 0.52 untreated vs. PTX-treated; P less than .05), and by 25% after 90 min of ischemia (6.84 +/- 0.49 vs. 4.84 +/- 0.42; P less than .05). The amount of protein leak was inversely related to ischemic blood flow, and the magnitude of this relationship was significantly reduced in PTX-treated animals. In arterial rings from untreated dogs exposed to 90 min of ischemia followed by reperfusion, there was impaired relaxation to ADP and acetylcholine, but not to sodium nitroprusside. However, relaxation in rings from the ischemic/reperfused vessel was significantly better in dogs treated with PTX. Collateral blood flow to the ischemic “at-risk” zone was not altered by PTX. Myeloperoxidase activity of ischemic reperfused myocardium, a measure of leukocyte accumulation, was reduced by PTX (myeloperoxidase = 1 .2 ± 0.2 vs. 0.8 ± 0.2 U/g myocardium, untreated vs. treated; P < .05), although still increased compared to nonischemic tissue (0.2 ± 0.2 U/g myocardium). We conclude that PTX diminishes coronary endothelial injury from ischemia and reperfusion, which is evident with increased permeability or impaired endothelium-dependent relaxation. This improvement is independent on the level of ischemic blood flow and is associated permeability or impaired endothelium-dependent relaxation. This improvement is independent on the level of ischemic blood flow and is associated with a decrease in myocardial leukocyte accumulation.
Details
- Title: Subtitle
- Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline
- Creators
- Ira M Dauber - University of Colorado HealthEdward J Lesenfsky - University of Colorado HealthRoger C Ashmore - University of Colorado HealthDouglas M Martel - University of Colorado HealthFrank M Sheridan - University of Colorado HealthJohn V Weil - University of Colorado HealthLawrence D Horwitz - University of Colorado Health
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.260(3), pp.1250-1256
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1016/S0022-3565(25)11436-5
- PMID
- 1312165
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Language
- English
- Date published
- 03/01/1992
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984656542002771
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