Heparin and the nonanticoagulant N-acetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung

Background. Ischemia-reperfusion injury of the lung frequently occurs after cardiopulmonary bypass, after pulmonary thromboendarterectomy, and especia lly after lung transplantation. Heparin is known to be protective in ischem ia-reperfusion injury but the risk for bleeding disorders may restrict its use in a variety of diseased conditions. Therefore, we tested the efficienc y of nonanticoagulant N-acetyl (NA) heparin to protect from post-ischemic r eperfusion injury of the lung. Methods. Pentobarbital-anesthetized, mechanically ventilated Lewis rats wer e heparinized (100 IU/kg) before insertion of catheters. Additionally, anim als received either heparin (200 IU/kg; n = 7), NA heparin (1.1 mg/kg; n = 7), or saline (control, n = 7) before ischemia. After normothermic ischemia for So minutes, the left lung was reperfused for 120 minutes, or until the death of the animal. The nonischemic right lung was excluded after 10 minu tes of reperfusion. Results. Survival rate at 120 minutes of reperfusion was 7 of 7 and 6 of 7 in the heparin and the NA-heparin group, but 0 in 7 in the control group (p < 0.01). At 30 minutes of reperfusion, PaO2 blood flow through the ascendi ng aorta and mean systemic blood pressure were also significantly higher in the heparin and the NA-heparin group when compared with the control group (p < 0.05). Pulmonary vascular resistance was significantly lower in the he parin and the NA-heparin groups, and histologic examination of the lungs fr om these groups confirmed reperfusion of nutritive alveolar capillaries by the presence of red blood cells. Lack of red blood cells in the alveolar ca pillaries of lung specimens from the control group indicated failure of cap illary reperfusion. Conclusions. Heparin and NA heparin exert similar protection against capill ary no-reflow after normothermic ischemia. of the lung. This implies that t he protective eff ect of heparin is mediated by properties different from i ts anticoagulant activity. Thus the nonanticoagulant N-acetyl heparin may p ose a safe new therapeutic approach in lung ischemia-reperfusion injury wit hout increasing the risk of hemorrhagic complications. (C) 2001 by The Soci ety of Thoracic Surgeons.