RELATIVE SUSCEPTIBILITY OF ENDOTHELIUM AND MYOCARDIAL-CELLS TO ISCHEMIA-REPERFUSION INJURY

We have investigated the timescale, extent and sequence of endothelial , myocardial and smooth muscle cell dysfunction following ischaemia-re perfusion in the isolated rat heart. Myocardial function in the form o f aortic flow was evaluated in the working heart preparation. Vasodila tation induced by endothelium-dependent agent 5-hydroxytryptamine (5-H T) 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 (endothelia l function vs. smooth muscle response) after a period of ischaemia was statistically analysed by Wilcoxon's signed rank test. A possible cor relation between structural and functional changes in coronary Vascula r endothelium after ischaemia was also explored by comparing endotheli al dysfunction with morphological assessment of endothelial damage see n after ischaemia. The experiments were performed at two clinically re levant temperatures of 20 degrees C and 4 degrees C. There was no sign ificant difference in the percentage recovery of aortic flow and 5-HT response or in 5-HT response and GTN effect after 30 min of unprotecte d ischaemia at 4 degrees C. The same duration of ischaemia al 20 OC le d 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 temp eratures caused significantly better recovery of aortic flow and GTN e ffect as compared with 5-HT response; 60 min of ischaemia protected by an infusion of a cardioplegic solution (protected ischaemia) at 4 deg rees C had no significant effect on the recovery of the three paramete rs. Periods of 90, 120, 180 and 240 min of protected ischaemia at 4 OC , and 60, 90 and 120 min of protected ischaemia at 20 degrees C result ed in significantly better recovery of aortic flow compared with 5HT r esponse and of GTN effect as compared to 5-HT response. This demonstra tes varying susceptibility of different cell types to ischaemic injury and highlights the strong vulnerability of endothelium to ischaemic d amage as compared with myocytes and smooth muscle cells. Furthermore, there was lack of correlation between post-ischaemic endothelial dysfu nction and microscopically assessed structural damage.