title: Relative susceptibility of endothelium and myocardial cells to ischaemia-reperfusion injury.
abstract: We have investigated the timescale, extent and sequence of endothelial, myocardial and smooth muscle cell dysfunction following ischaemia-reperfusion in the isolated rat heart. Myocardial function in the form of aortic flow was evaluated in the working heart preparation. Vasodilatation induced by endothelium-dependent agent 5-hydroxytryptamine (5-HT) and endothelium-independent substance glyceryl trinitrate (GTN) was used to assess endothelial and smooth muscle function, respectively. The percentage recovery of 5-HT response and aortic flow (endothelial vs. myocardial function) plus 5-HT response and GTN effect (endothelial function vs. smooth muscle response) after a period of ischaemia was statistically analysed by Wilcoxon's signed rank test. A possible correlation between structural and functional changes in coronary vascular endothelium after ischaemia was also explored by comparing endothelial dysfunction with morphological assessment of endothelial damage seen after ischaemia. The experiments were performed at two clinically relevant temperatures of 20 degrees C and 4 degrees C. There was no significant difference in the percentage recovery of aortic flow and 5-HT response or in 5-HT response and GTN effect after 30 min of unprotected ischaemia at 4 degrees C. The same duration of ischaemia at 20 degrees C led to significantly better recovery of GTN effect as compared with 5-HT response, but there was no difference in the recovery of aortic flow and 5-HT response. Sixty minutes of unprotected ischaemia at both temperatures caused significantly better recovery of aortic flow and GTN effect as compared with 5-HT response; 60 min of ischaemia protected by an infusion of a cardioplegic solution (protected ischaemia) at 4 degrees C had no significant effect on the recovery of the three parameters. Periods of 90, 120, 180 and 240 min of protected ischaemia at 4 degrees C, and 60, 90 and 120 min of protected ischaemia at 20 degrees C resulted in significantly better recovery of aortic flow compared with 5-HT response and of GTN effect as compared to 5-HT response. This demonstrates varying susceptibility of different cell types to ischaemic injury and highlights the strong vulnerability of endothelium to ischaemic damage as compared with myocytes and smooth muscle cells. Furthermore, there was lack of correlation between post-ischaemic endothelial dysfunction and microscopically assessed structural damage.
authors.affiliation: Department of Cardiac Surgery, National Heart and Lung Institute, London, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Mankad
authors.forename: M
authors.initials: M
authors.lastname: Amrani
authors.forename: S
authors.initials: S
authors.lastname: Rothery
authors.forename: N J
authors.initials: NJ
authors.lastname: Severs
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D007036:Hypothermia, Induced; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009130:Muscle, Smooth / Q000098:blood supply / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D012701:Serotonin; D005996:Nitroglycerin