Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart.

ABSTRACT

BACKGROUND: Ventricular dysfunction after long cardioplegic arrest has been observed in cardiac operations. Urinary trypsin inhibitor, also called ulinastatin, may attenuate myocardial ischemia-reperfusion injury. The present study was designed to determine the protective efficacy of ulinastatin in blood-perfused parabiotic isolated rabbit hearts as a surgically relevant model with long (4-hour) cardioplegic arrest. METHODS: Each isolated rabbit heart, with a latex balloon inserted in the left ventricle, was parabiotically blood-perfused using a modified Langendorff column. The left ventricular developed pressure, rate of pressure development, and coronary flow with a left ventricular end-diastolic pressure of 10 mm Hg were measured before ischemia and 15, 30, 45, and 60 minutes after reperfusion began (control, n = 10). Ulinastatin (15,000 U/kg) was administered to the support animal just before reperfusion began (group U-1, n = 10) or at the beginning of the extracorporeal circulation and readministered before reperfusion (group U-2, n = 10). The endothelium of the coronary artery was observed by scanning electron microscopy to evaluate the extent of endothelial ischemia-reperfusion injury. RESULTS: Ulinastatin enhanced the recovery of developed pressure in both the U-1 (p<0.05) and U-2 (p < 0.01) groups compared with the control group. Although ulinastatin given just before reperfusion (group U-1) did not enhance the recovery of the rate of pressure development or the coronary flow compared with the control, earlier administration did improve the recovery of the rate of pressure development compared with the control (U-2, p<0.05), and there was improvement of the recovery of coronary flow after 60 minutes of reperfusion (U-2, p<0.05). Scanning electron microscopy showed that ulinastatin had ameliorated coronary endothelial damage. CONCLUSIONS: Ulinastatin improved functional recovery after long cardioplegic arrest and reduced coronary endothelial injury. Administration of ulinastatin at the beginning of cardiopulmonary bypass and just before reperfusion may be useful clinically in cases requiring prolonged aortic cross-clamping.