EFFECTS OF CARDIOPLEGIA ON VASCULAR FUNCTION AND THE NO-REFLOW PHENOMENON AFTER ISCHEMIA AND REPERFUSION - STUDIES IN THE ISOLATED BLOOD-PERFUSED RAT-HEART

The ability of cardioplegia to protect against cardiac contractile dys function caused by ischemia and reperfusion is well established. The e ffects of cardioplegia on vascular injury and the no-reflow phenomenon , however, remain controversial. We used the blood-perfused rat heart to study the effect of St. Thomas' Hospital cardioplegic solution on p ostischemic endothelium-dependent and endothelium-independent vascular function, the extent of the no-reflow phenomenon, and the temporal re lationship between postischemic vascular and contractile function. Iso lated rat hearts (16 per group) perfused with blood from a support rat at 60 mm Hg were subjected to 10, 20, 30 or 40 minutes of global isch emia and 40 minutes of reperfusion at 37 degrees C. Eight hearts in ea ch group also received cardioplegia (45 mm Hg for 2 minutes) before is chemia. Left ventricular developed pressure was measured with an intra ventricular balloon. At the end of reperfusion, a bolus of 250 mu g ni tro-L-arginine methyl ester was infused to assess endothelium dependen t vascular function. After a 20-minute washout, 25 mu g sodium nitropr usside was infused to assess endothelium-independent vascular function . Fluorescein (1 mi, 1% weight/volume) was then infused to assess no-r eflow; this involved freezing the hearts, cutting them into transverse sections (10 x 1 mm), video recording the sections under ultraviolet light, digitizing the images, and analyzing density of fluorescence. N o-reflow was defined as a flow of less than 5%. Compared with nonische mic control responses, endothelium-independent vascular function was s ignificantly decreased only after 30 and 40 minutes of ischemia (48.1% +/- 3.8% and 24.3% +/- 7.4%, p < 0.05), but it was significantly prot ected by cardioplegia (66.6% +/- 3.9% and 64.5% +/- 5.2%, p < 0.05). A significant reduction in endothelium-dependent vascular function was observed after 40 minutes of ischemia (-31.8% +/- 6.6% vs -50.4% +/- 1 .6% in control hearts, p < 0.05), and again this was improved by cardi oplegia (-45.0% +/- 3.4%, p < 0.05 vs ischemic group). Areas of no ref low were present after 30 and 40 minutes of ischemia (11.9% +/- 6.8% a nd 33.4% +/- 14.1% of left ventricular mass), and at each time period they were significantly decreased by cardioplegia (0.7% +/- 0.4% and 3 .8% +/- 1.6%, p < 0.05). Postischemic contractile dysfunction was obse rved before any vascular alteration was apparent, After only 20 minute s of ischemia, the postischemic recovery of left ventricular developed pressure fell to 56.7% +/- 4.0%, but both endothelium-dependent vascu lar function and endothelium-independent vascular function were unaffe cted, In conclusion, vascular alterations are apparent only after prol onged periods of ischemia, longer than those required to observe contr actile dysfunction, and cardioplegia protects against postischemic end othelium-dependent and endothelium-independent vascular dysfunction an d reduces the extent of the no-reflow phenomenon.