|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2005; 45:1287-1291, doi:10.1016/j.jacc.2005.01.021 © 2005 by the American College of Cardiology Foundation |
Hatter Institute and Centre for Cardiology, University College London Hospital and Medical School, London, United Kingdom.
Manuscript received October 5, 2004; revised manuscript received November 1, 2004, accepted January 4, 2005.
* Reprint requests and correspondence to: Prof. Derek M. Yellon, The Hatter Institute and Centre for Cardiology, University College London Hospital, Grafton Way, London WC1E 6DB, United Kingdom. (Email: d.yellon{at}ucl.ac.uk).
OBJECTIVES: We sought to ascertain whether chronic oral therapy with atorvastatin protects against ischemia/reperfusion (I/R) injury.
BACKGROUND: We have recently shown that acute atorvastatin treatment protects against reperfusion-induced injury by activating the PI3K/Akt/eNOS pathway. However, many patients are on chronic statin therapy, and it is necessary to investigate whether this, in itself, provides a therapeutic advantage.
METHODS: Sprague-Dawley rats were orally treated for one day, three days, one week, or two weeks with 20 mg/kg of atorvastatin or vehicle, after which the hearts underwent 35 min of ischemia and 120 min reperfusion (IR). Two additional groups were treated for one or two weeks with atorvastatin and then received a supplementary dose of 40 mg/kg before IR. The risk zone was determined using Evans blue and infarct size (IR%) using triphenyltetrazolium chloride staining.
RESULTS: Treatment with atorvastatin for one and three days significantly reduced infarct size versus controls (38.9 ± 3.1% vs. 56.4 ± 2.3%; 39.3 ± 2.4% vs. 61.3 ± 3.8%, respectively). However, after one or two weeks of treatment, no protection was observed (52.6 ± 3.8% vs. 58.6 ± 4.3%; 58.3 ± 2.7% vs. 52.4 ± 5.7%, respectively). Surprisingly, a supplementary dose of atorvastatin recaptured the protection in the groups treated chronically (36.2 ± 2.8% vs. 58.6 ± 4.3%; 26.8 ± 1.5% vs. 51.2 ± 6.7%, at one and two weeks, respectively). Interestingly, we observed an increased level of phosphatase and tensin homolog deleted on chromosome ten (PTEN), the phosphatidylinositol-3 kinase inhibitor, in the chronic treated hearts.
CONCLUSIONS: In conclusion, atorvastatin appears to have an acute protective effect that wanes with time associated with an increase in PTEN levels. This waning protection can be recaptured by an acute high dose given immediately before IR. These results may have protential clinical relevance.
| ||||||
Related Article
J. Am. Coll. Cardiol. 2005 45: 1292-1294.
This article has been cited by other articles:
|
|
 |
|
  Y. Ye, J. D. Martinez, R. J. Perez-Polo, Y. Lin, B. F. Uretsky, and Y. Birnbaum The role of eNOS, iNOS, and NF-{kappa}B in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H343 - H351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yin, J. Zhu, Z. Wang, H. Huang, J. Qian, Z. Li, and H. Jing Simvastatin attenuates cardiac isograft ischemia-reperfusion injury by down-regulating CC chemokine receptor-2 expression J. Thorac. Cardiovasc. Surg., September 1, 2007; 134(3): 780 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Merla, Y. Ye, Y. Lin, S. Manickavasagam, M.-H. Huang, R. J. Perez-Polo, B. F. Uretsky, and Y. Birnbaum The central role of adenosine in statin-induced ERK1/2, Akt, and eNOS phosphorylation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1918 - H1928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, Y. Lin, R. Perez-Polo, M.-H. Huang, M. G. Hughes, D. J. McAdoo, S. Manickavasagam, B. F. Uretsky, and Y. Birnbaum Enhanced cardioprotection against ischemia-reperfusion injury with a dipyridamole and low-dose atorvastatin combination Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H813 - H818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Patti, V. Pasceri, G. Colonna, M. Miglionico, D. Fischetti, G. Sardella, A. Montinaro, and G. Di Sciascio Atorvastatin Pretreatment Improves Outcomes in Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Coronary Intervention: Results of the ARMYDA-ACS Randomized Trial J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1272 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, Y. Lin, S. Atar, M.-H. Huang, J. R. Perez-Polo, B. F. Uretsky, and Y. Birnbaum Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1158 - H1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, D. Berman, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, W. Y.W. Lew, D. Sahn, and S. Tsimikas Highlights of the Year in JACC 2005 J. Am. Coll. Cardiol., January 3, 2006; 47(1): 184 - 202. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Cai and G. L. Semenza PTEN Activity Is Modulated During Ischemia and Reperfusion: Involvement in the Induction and Decay of Preconditioning Circ. Res., December 9, 2005; 97(12): 1351 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrmann Peri-procedural myocardial injury: 2005 update Eur. Heart J., December 1, 2005; 26(23): 2493 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Bonvini, T. Hendiri, and E. Camenzind Inflammatory response post-myocardial infarction and reperfusion: a new therapeutic target? Eur. Heart J. Suppl., October 1, 2005; 7(suppl_I): I27 - I36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schulz Pleiotropic effects of statins: Acutely good, but chronically bad? J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1292 - 1294. [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
