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The ADP receptor P2Y(1) mediates t-PA release in pigs during cardiac ischemia.

Olivecrona, Göran LU ; Götberg, Matthias LU ; Harnek, Jan LU ; Jacobson, Kenneth; Jern, Sverker and Erlinge, David LU (2007) In Journal of Thrombosis and Thrombolysis 24(2). p.115-122
Abstract
Background The endothelial ADP receptor P2Y(1) is responsible for a large part of the reactive hyperemia following cardiac ischemia. Tissue plasminogen activator (t-PA) increases during reactive hyperemia. We postulated that the release of t-PA during reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor. Methods t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus in a porcine model. The stable ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery through the tip of a coronary angioplasty balloon. In separate pigs the... (More)
Background The endothelial ADP receptor P2Y(1) is responsible for a large part of the reactive hyperemia following cardiac ischemia. Tissue plasminogen activator (t-PA) increases during reactive hyperemia. We postulated that the release of t-PA during reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor. Methods t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus in a porcine model. The stable ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery through the tip of a coronary angioplasty balloon. In separate pigs the coronary artery was occluded with the balloon for 10 min. During the first and tenth minute of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion in 8 pigs, 10 pigs were used as controls. Results 2-MeSADP increased levels of t-PA in the coronary sinus, which could be significantly inhibited by co-infusion with MRS2179. During cardiac ischemia and reperfusion, t-PA increased significantly, an effect that could be significantly inhibited by MRS2179. Conclusions Intra coronary administered MRS2179, a selective P2Y(1) receptor blocker, significantly reduces the increased levels of t-PA caused by both 2-MeSADP and cardiac ischemia in coronary arteries. Thus, ADP acting on the endothelial P2Y(1) receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
P2Y1, ADP, t-PA, ischemia, coronary
in
Journal of Thrombosis and Thrombolysis
volume
24
issue
2
pages
115 - 122
publisher
Springer
external identifiers
  • wos:000248794000006
  • scopus:36348980838
ISSN
1573-742X
DOI
10.1007/s11239-007-0010-3
language
English
LU publication?
yes
id
cfbd0a31-c519-4e66-8ee8-34a86b54b3c8 (old id 165751)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17294140&dopt=Abstract
date added to LUP
2007-07-11 13:18:32
date last changed
2017-01-22 04:02:29
@article{cfbd0a31-c519-4e66-8ee8-34a86b54b3c8,
  abstract     = {Background The endothelial ADP receptor P2Y(1) is responsible for a large part of the reactive hyperemia following cardiac ischemia. Tissue plasminogen activator (t-PA) increases during reactive hyperemia. We postulated that the release of t-PA during reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor. Methods t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus in a porcine model. The stable ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery through the tip of a coronary angioplasty balloon. In separate pigs the coronary artery was occluded with the balloon for 10 min. During the first and tenth minute of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion in 8 pigs, 10 pigs were used as controls. Results 2-MeSADP increased levels of t-PA in the coronary sinus, which could be significantly inhibited by co-infusion with MRS2179. During cardiac ischemia and reperfusion, t-PA increased significantly, an effect that could be significantly inhibited by MRS2179. Conclusions Intra coronary administered MRS2179, a selective P2Y(1) receptor blocker, significantly reduces the increased levels of t-PA caused by both 2-MeSADP and cardiac ischemia in coronary arteries. Thus, ADP acting on the endothelial P2Y(1) receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP.},
  author       = {Olivecrona, Göran and Götberg, Matthias and Harnek, Jan and Jacobson, Kenneth and Jern, Sverker and Erlinge, David},
  issn         = {1573-742X},
  keyword      = {P2Y1,ADP,t-PA,ischemia,coronary},
  language     = {eng},
  number       = {2},
  pages        = {115--122},
  publisher    = {Springer},
  series       = {Journal of Thrombosis and Thrombolysis},
  title        = {The ADP receptor P2Y(1) mediates t-PA release in pigs during cardiac ischemia.},
  url          = {http://dx.doi.org/10.1007/s11239-007-0010-3},
  volume       = {24},
  year         = {2007},
}