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 micrograms 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.
Kenny
D
D
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Coughlan
M G
MG
Pagel
P S
PS
Kampine
J P
JP
Warltier
D C
DC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D008297:Male; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012008:Recurrence; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000109:Acetylcholine