(Circulation. 2000;101:1165.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Troglitazone Improves Recovery of Left Ventricular Function After Regional Ischemia in Pigs
From the Cardiology Section, Veterans Affairs Medical Center and University of Colorado Health Sciences Center (L.L., Y.X., G.G.S.), Denver, Colo, and Cardiovascular Research Institute, University of California (P.Z.), San Francisco, Calif.
Correspondence to Gregory Schwartz, MD, PhD, Cardiology Section (111B), VA Medical Center, 1055 Clermont St, Denver, CO 80220. E-mail Gregory.Schwartz{at}med.va.gov
Background—This study determined whether treatment of normal (nondiabetic) pigs with the insulin-sensitizing agent troglitazone improves recovery of left ventricular (LV) function after acute ischemia and whether such effects are associated with altered myocardial substrate metabolism.
Methods and Results—Juvenile pigs (n=6) were treated with troglitazone (75 mg · kg-1 · d-1 PO) for 8 weeks. Untreated pigs (n=8) served as controls. Under anesthetized, open-chest conditions, pigs underwent 90 minutes of moderate regional LV ischemia and 90 minutes of reperfusion. Regional LV function was assessed with subendocardial sonomicrometry crystals. Fasting plasma insulin and free fatty acid levels were lower in troglitazone-treated pigs than in untreated pigs, whereas blood glucose did not differ between groups. These findings suggest that treatment enhanced systemic insulin sensitivity. Baseline hemodynamics and regional LV function did not differ between groups. After ischemia and reperfusion, systolic function (external work) of the ischemic region recovered to 44±6% of baseline in troglitazone-treated pigs versus 18±6% of baseline in untreated pigs (P<0.05). Regional diastolic function (maximum rate of wall expansion) recovered to 78±7% of baseline in treated pigs versus 52±7% of baseline in untreated pigs (P<0.05). Recovery of global LV systolic and diastolic function was also significantly greater in treated pigs. Myocardial glucose uptake did not differ between groups under any condition; however, net myocardial lactate uptake after reperfusion was 7 times greater in troglitazone-treated pigs than in untreated pigs, suggesting that treatment enhanced myocardial carbohydrate oxidation after reperfusion.
Conclusions—In nondiabetic pigs, chronic troglitazone treatment improves recovery of LV systolic and diastolic function after acute ischemia.
Key Words: metabolism • drugs • ischemia • myocardial contraction • diastole
This article has been cited by other articles:
 |
|
 |
|
  H Kaneda, T Shiono, Y Miyashita, S Takahashi, Y Taketani, H Domae, J Matsumi, S Mizuno, Y Minami, K Sugitatsu, et al. Efficacy and safety of pioglitazone in patients with ST elevation myocardial infarction treated with primary stent implantation Heart, July 1, 2009; 95(13): 1079 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 Y. Taniguchi, T. Ooie, N. Takahashi, T. Shinohara, M. Nakagawa, H. Yonemochi, M. Hara, H. Yoshimatsu, and T. Saikawa Pioglitazone but not glibenclamide improves cardiac expression of heat shock protein 72 and tolerance against ischemia/reperfusion injury in the heredity insulin-resistant rat. Diabetes, August 1, 2006; 55(8): 2371 - 2378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Molavi, J. Chen, and J. L. Mehta Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H687 - H693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rocic, B. Rezk, and P. A. Lucchesi PPAR-{gamma} agonists decrease hyperhomcysteinemia and cardiac dysfunction: new hope for ailing diabetic hearts? Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H26 - H28. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Verreth, J. Ganame, A. Mertens, H. Bernar, M.-C. Herregods, and P. Holvoet Peroxisome Proliferator-Activated Receptor-{alpha},{gamma}-Agonist Improves Insulin Sensitivity and Prevents Loss of Left Ventricular Function in Obese Dyslipidemic Mice Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 922 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Berg, B. O. Christensen, S. Aagaard, T. B.N. Christensen, D. A. Steinbruchel, and J. M. Hasenkam Ischaemic preconditioning causes increased myocardial vascular resistance but no myocardial contractility changes in pigs after OPCAB Interactive CardioVascular and Thoracic Surgery, June 1, 2005; 4(3): 207 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Abdelrahman, A. Sivarajah, and C. Thiemermann Beneficial effects of PPAR-{gamma} ligands in ischemia-reperfusion injury, inflammation and shock Cardiovasc Res, March 1, 2005; 65(4): 772 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Peroxisome proliferator-activated receptors and cardiovascular remodeling Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1037 - H1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, M. Gen, L. Lu, J. Fox, S. O. Weiss, R. D. Brown, D. Perlov, H. Ahmad, P. Zhu, C. Greyson, et al. PPAR-{gamma} activation fails to provide myocardial protection in ischemia and reperfusion in pigs Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1314 - H1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Masoudi, S. E. Inzucchi, Y. Wang, E. P. Havranek, J. M. Foody, and H. M. Krumholz Thiazolidinediones, Metformin, and Outcomes in Older Patients With Diabetes and Heart Failure: An Observational Study Circulation, February 8, 2005; 111(5): 583 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-L. Yue, W. Bao, J.-L. Gu, J. Cui, L. Tao, X.-L. Ma, E. H. Ohlstein, and B. M. Jucker Rosiglitazone Treatment in Zucker Diabetic Fatty Rats Is Associated With Ameliorated Cardiac Insulin Resistance and Protection From Ischemia/Reperfusion-Induced Myocardial Injury Diabetes, February 1, 2005; 54(2): 554 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-M. Lee and T.-F. Chou Troglitazone administration limits infarct size by reduced phosphorylation of canine myocardial connexin43 proteins Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1650 - H1659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Schiffrin, F. Amiri, K. Benkirane, M. Iglarz, and Q. N. Diep Peroxisome Proliferator-Activated Receptors: Vascular and Cardiac Effects in Hypertension Hypertension, October 1, 2003; 42(4): 664 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, L. Lu, C. Greyson, J. Lee, M. Gen, K. Kinugawa, C. S. Long, and G. G. Schwartz Deleterious Effects of Acute Treatment With a Peroxisome Proliferator-Activated Receptor-{gamma} Activator in Myocardial Ischemia and Reperfusion in Pigs Diabetes, May 1, 2003; 52(5): 1187 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Kelly PPARs of the Heart: Three Is a Crowd Circ. Res., March 21, 2003; 92(5): 482 - 484. [Full Text] [PDF]
|
|
|
|
|
|
E. Aasum, A. D. Hafstad, D. L. Severson, and T. S. Larsen Age-Dependent Changes in Metabolism, Contractile Function, and Ischemic Sensitivity in Hearts From db/db Mice Diabetes, February 1, 2003; 52(2): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Khandoudi, P. Delerive, I. Berrebi-Bertrand, R. E. Buckingham, B. Staels, and A. Bril Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-{gamma}, Inhibits the Jun NH2-Terminal Kinase/Activating Protein 1 Pathway and Protects the Heart From Ischemia/Reperfusion Injury Diabetes, May 1, 2002; 51(5): 1507 - 1514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Sidell, M. A. Cole, N. J. Draper, M. Desrois, R. E. Buckingham, and K. Clarke Thiazolidinedione Treatment Normalizes Insulin Resistance and Ischemic Injury in the Zucker Fatty Rat Heart Diabetes, April 1, 2002; 51(4): 1110 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Molavi, N. Rasouli, and J. L. Mehta Peroxisome Proliferator-Activated Receptor Ligands as Antiatherogenic Agents: Panacea or Another Pandora's Box? Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 1 - 8. [Abstract] [PDF]
|
|
|
|
|
|
T.-l. Yue, J. Chen, W. Bao, P. K. Narayanan, A. Bril, W. Jiang, P. G. Lysko, J.-L. Gu, R. Boyce, D. M. Zimmerman, et al. In Vivo Myocardial Protection From Ischemia/Reperfusion Injury by the Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Rosiglitazone Circulation, November 20, 2001; 104(21): 2588 - 2594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Taegtmeyer Metabolism--the lost child of cardiology J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1386 - 1388. [Full Text] [PDF]
|
|