title: Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Cardiology, University of Colorado Health Sciences Center, Denver.
authors.forename: I M
authors.initials: IM
authors.lastname: Dauber
authors.forename: E J
authors.initials: EJ
authors.lastname: Lesnefsky
authors.forename: R C
authors.initials: RC
authors.lastname: Ashmore
authors.forename: D M
authors.initials: DM
authors.lastname: Martel
authors.forename: F M
authors.initials: FM
authors.lastname: Sheridan
authors.forename: J V
authors.initials: JV
authors.lastname: Weil
authors.forename: L D
authors.initials: LD
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010431:Pentoxifylline / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis
chemical_list: D001798:Blood Proteins; D009195:Peroxidase; D010431:Pentoxifylline