ENDOTHELIN-1 AND MYOCARDIAL PRECONDITIONING

This study attempted to define the role of endothelin (ET) in precondi tioning. We previously showed that ET is produced during myocardial is chemia and reperfusion. Because both preconditioning and ET act throug h protein kinase C, ET could play a role in preconditioning. Dogs were randomized to three groups subjected to 40 minutes of ischemia, with (groups A end B) or without (group C) preconditioning, followed by 4 h ours of reperfusion. Groups A and C received saline infusions; group B received continuous infusions of the ET(A)-selective antagonist FR139 317. Both preconditioned groups had smaller infarct sizes (group A, 7. 9% +/- 2.5%; group B, 8.4% +/- 2.6%) than the nonpreconditioned group (group C, 16.2% +/- 3.3%). Administration of the ET(A) antagonist FR13 9317 did not alter infarct size. This study demonstrated that ET(A)-re ceptor blockade did not alter infarct size in preconditioned animals a nd suggests that endothelin does not play a significant role in this p rocess.