title: Transforming growth factor beta 1 preserves endothelial function after multiple brief coronary artery occlusions and reperfusion.
abstract: 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.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: D
authors.initials: D
authors.lastname: Kenny
authors.forename: M G
authors.initials: MG
authors.lastname: Coughlan
authors.forename: P S
authors.initials: PS
authors.lastname: Pagel
authors.forename: J P
authors.initials: JP
authors.lastname: Kampine
authors.forename: D C
authors.initials: DC
authors.lastname: Warltier
mesh_terms: 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*
chemical_list: D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000109:Acetylcholine