BLOOD CARDIOPLEGIA ENHANCED WITH NITRIC-OXIDE DONOR SPM-5185 COUNTERACTS POSTISCHEMIC ENDOTHELIAL AND VENTRICULAR DYSFUNCTION

This study tested the hypothesis that enhancement of blood cardioplegi a with the nitric oxide donor agent SPM-5185 inhibits postischemic lef t ventricular and coronary endothelial dysfunction, Eighteen anestheti zed dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4 degrees C multidose blood card ioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood cardioplegia with 1 mu mol/L SPM-5185 (low-dose g roup; n = 6), or 10 mu mol/L SPM-5185 (high-dose group; n = 6), After 60 minutes of cardioplegic arrest, the heart was reperfused for a tota l of 60 minutes, first in the beating empty state for 30 minutes and t hen after discontinuation of bypass for 30 minutes, Baseline and posti schemic left ventricular function was assessed by the slope of the end -systolic pressure-volume (impedance catheter) relation, Postischemic end-systolic pressure-volume relation was depressed by 53.7% of preisc hemic values in the vehicle group (from 8.2 +/- 1.0 to 3.8 +/- 0.3 mm Hg/ml) and by 33.7% (from 9.2 +/- 1.1 to 6.1 +/- 0.5 mm Hg/ml) in the low-dose group, In contrast, there was complete postischemic functiona l recovery in the high-dose group (from 7.6 +/- 1.1 to 7.2 +/- 1.2 mm Hg/ml), In coronary arteries isolated from these hearts, endothelium-d ependent maximal relaxation to acetylcholine was impaired by 27% in th e vehicle group and by 18% in the low-dose group, whereas the high-dos e group showed complete endothelium-dependent relaxation, Myeloperoxid ase activity, an index of neutrophil accumulation in postischemic myoc ardium, was elevated in the vehicle and low-dose groups (3.36 +/- 0.58 and 2.56 +/- 0.68 U/100 mg tissue) but was significantly reduced in t he high-dose group to 1.27 +/- 0.45 U/100 mg tissue, We conclude that inclusion of 10 mu mol/L nitric oxide donor SPM-5185 in blood cardiopl egia improves postischemic ventricular performance and endothelial fun ction in ischemically injured hearts, possibly via inhibition of neutr ophil-mediated damage.