TRANSFORMING GROWTH-FACTOR BETA(1) PRESERVES ENDOTHELIAL FUNCTION AFTER MULTIPLE BRIEF CORONARY-ARTERY OCCLUSIONS AND REPERFUSION

The objective of this investigation was to determine the effect of transforming growth factor beta(1) (TGF-beta(1)) on endothelium-dependent relaxation in isolated epicardial coronary artery rings obtained from anesthetized dogs after multiple brief episodes of coronary artery occlusion and reperfusion in vivo. Dogs were subjected to four 5-minute periods of left anterior descending coronary artery occlusion interspersed with 5 minutes of reperfusion and followed by a final 1-hour period of reperfusion. Normal left circumflex coronary arteries were used as control samples. Repetitive ischemia and reperfusion significantly (p < 0.01) inhibited the relaxation response to acetylcholine in rings preconstricted with potassium. In an additional group of dogs subjected to the same protocol, 10 mu g of human recombinant TGF-beta(1) was infused into the left anterior descending coronary artery distal to the site of occlusion via a diagonal branch at 0.3 ml/min immediately before and during the repetitive occlusions and reperfusions. TGF-beta(1) prevented impaired endothelium-dependent relaxation after multiple brief occlusions and reperfusions. These results demonstrate a protective role for TGF-beta(1) in the endothelial injury that occurs during repeated episodes of coronary artery occlusion and reperfusion.