Ps. Mankad et al., RELATIVE SUSCEPTIBILITY OF ENDOTHELIUM AND MYOCARDIAL-CELLS TO ISCHEMIA-REPERFUSION INJURY, Acta Physiologica Scandinavica, 161(1), 1997, pp. 103-112
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.