AJP - Heart pressure measurements
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (November 4, 2004). doi:10.1152/ajpheart.00618.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/3/H1314    most recent
00618.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (20)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xu, Y.
Right arrow Articles by Schwartz, G. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, Y.
Right arrow Articles by Schwartz, G. G.
Submitted on June 22, 2004
Accepted on November 2, 2004

PPAR- {gamma} activation fails to provide myocardial protection in ischemia and reperfusion in pigs

Ya Xu1, Michael Gen1, Li Lu1, Jennifer Fox1, Sarah O. Weiss1, R. Dale Brown1, Daniel Perlov1, Hasan Ahmad1, Peili Zhu1, Clifford Greyson1, Carlin S. Long1, and Gregory G. Schwartz1*

1 Cardiology Section, VA Medical Center and University of Colorado Health Sciences Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: Gregory.Schwartz{at}med.va.gov.

Peroxisome proliferator-activated receptor-gamma (PPAR-{gamma}) modulates substrate metabolism and inflammatory responses. In experimental myocardial ischemia and reperfusion (I/R) in rats, thiazolidinedione PPAR-{gamma} activators reduce infarct size and preserve left ventricular function. To date, only troglitazone has been shown to be protective in I/R in large animals. However, because troglitazone contains both {alpha}-tocopherol and thiazolidinedione moieties it remains uncertain whether PPAR-{gamma} activation per se is protective in myocardial I/R in large animals. To address this question, 56 pigs were treated orally for 8 weeks with troglitazone 75 mg/kg/d, rosiglitazone 3 mg/kg/d, {alpha}-tocopherol 73 mg/kg/d (equimolar to troglitazone dose), or received no treatment. Pigs were then anesthetized and subjected to 90 min low flow regional myocardial ischemia and 90 min reperfusion. Myocardial expression of PPAR-{gamma}, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of pro-inflammatory cytokines during I/R, compared with untreated pigs. In contrast, pigs treated with troglitazone or {alpha}-tocopherol had greater preservation of myocardial contractile function and lactate uptake and attenuated cytokine expression, compared to untreated pigs. Multivariate analysis indicated that presence of an {alpha}-tocopherol moiety, but not a thiazolidinedione moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-{gamma} activation is not protective in a porcine model of myocardial I/R. The protective effects of troglitazone is attributable to its {alpha}-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest interspecies differences in the response to PPAR-{gamma} activation in the heart.




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
E. D. Abel, S. E. Litwin, and G. Sweeney
Cardiac Remodeling in Obesity
Physiol Rev, April 1, 2008; 88(2): 389 - 419.
[Abstract] [Full Text] [PDF]

Home page
 J ANIM SCIHome page
G. J. Hausman, S. P. Poulos, T. D. Pringle, and M. J. Azain
The influence of thiazolidinediones on adipogenesis in vitro and in vivo: Potential modifiers of intramuscular adipose tissue deposition in meat animals
J Anim Sci, April 1, 2008; 86(14_suppl): E236 - E243.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
N. A. Turner, R. S. Mughal, P. Warburton, D. J. O'Regan, S. G. Ball, and K. E. Porter
Mechanism of TNF{alpha}-induced IL-1{alpha}, IL-1{beta} and IL-6 expression in human cardiac fibroblasts: Effects of statins and thiazolidinediones
Cardiovasc Res, October 1, 2007; 76(1): 81 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
B. N. Finck
The PPAR regulatory system in cardiac physiology and disease
Cardiovasc Res, January 15, 2007; 73(2): 269 - 277.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Xu, L. Lu, C. Greyson, M. Rizeq, K. Nunley, B. Wyatt, M. R. Bristow, C. S. Long, and G. G. Schwartz
The PPAR-{alpha} activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs
Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1798 - H1807.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
S. E. Nissen, K. Wolski, and E. J. Topol
Effect of Muraglitazar on Death and Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus
JAMA, November 23, 2005; 294(20): 2581 - 2586.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.