The ability of
cardioplegia to protect against cardiac contractile dysfunction caused by
ischemia and reperfusion is well established. The effects 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 postischemic endothelium-dependent and endothelium-independent vascular function, the extent of the
no-reflow phenomenon, and the temporal relationship between postischemic vascular and contractile function. Isolated 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
ischemia and 40 minutes of reperfusion at 37 degrees C. Eight hearts in each group also received
cardioplegia (45 mm Hg for 2 minutes) before
ischemia. Left ventricular developed pressure was measured with an intraventricular balloon. At the end of reperfusion, a bolus of 250 micrograms nitro-
L-arginine methyl ester was infused to assess endothelium dependent vascular function. After a 20-minute washout, 25 micrograms
sodium nitroprusside was infused to assess endothelium-independent vascular function.
Fluorescein (1 ml, 1% weight/volume) was then infused to assess no-reflow; 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. No-reflow was defined as a flow of less than 5%. Compared with nonischemic control responses, endothelium-independent vascular function was significantly 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 protected 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
cardioplegia (-45.0% +/- 3.4%, p < 0.05 vs ischemic group). Areas of no reflow were present after 30 and 40 minutes of
ischemia (11.9% +/- 6.8% and 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 observed before any vascular alteration was apparent. After only 20 minutes of
ischemia, the postischemic recovery of left ventricular developed pressure fell to 56.7% +/- 4.0%, but both endothelium-dependent vascular function and endothelium-independent vascular function were unaffected. In conclusion, vascular alterations are apparent only after prolonged periods of
ischemia, longer than those required to observe contractile dysfunction, and
cardioplegia protects against postischemic endothelium-dependent and endothelium-independent vascular dysfunction and reduces the extent of the
no-reflow phenomenon.