Published online before print October 3, 2002, doi: 10.1161/01.RES.0000040396.79379.77
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 3, 2002
Revised on September 23, 2002
Accepted on September 25, 2002
Dissociation of Regional Adaptations to Ischemia and Global Myolysis in an Accelerated Swine Model of Chronic Hibernating Myocardium
Salome A. Thomas ;
From the VA Western New York Healthcare System, Buffalo, NY; the Department of Medicine and the Department of Physiology and Biophysics, University of New York at Buffalo; and the Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, the Netherlands.
* To whom correspondence should be addressed. E-mail: canty{at}buffalo.edu.
We tested the hypothesis that an acute critical limitation in coronary flow reserve could rapidly recapitulate the physiological, molecular, and morphological phenotype of hibernating myocardium. Chronically instrumented swine were subjected to a partial occlusion to produce acute stunning, followed by reperfusion through a critical stenosis. Stenosis severity was adjusted serially so that hyperemic flow was severely reduced yet always higher than the preocclusion resting level. After 24 hours, resting left anterior descending coronary artery (LAD) wall thickening had decreased from 36.3±4.0% to 25.5±3.7% (P<0.05), whereas resting flow had remained normal (67±6 versus 67±8 mL/min, respectively). Although peak hyperemic flow exceeded the prestenotic value, resting flow (45±10 mL/min) and LAD wall thickening (17.0±5.0%) progressively decreased after 2 weeks, when physiological features of hibernating myocardium had developed. Regional reductions in sarcoplasmic reticulum proteins were present in hibernating myocardium but absent in stunned myocardium evaluated after 24 hours. Histological analysis showed an increase in connective tissue along with myolysis (myofibrillar loss per myocyte >10%) and increased glycogen typical of hibernating myocardium in the LAD region (33±3% of myocytes from animals with hibernating myocardium versus 15±4% of myocytes from sham-instrumented animals, P<0.05). Surprisingly, the frequency of myolysis was similar in normally perfused remote regions from animals with hibernating myocardium (32±7%). We conclude that the regional physiological and molecular characteristics of hibernating myocardium develop rapidly after a critical limitation in flow reserve. In contrast, the global nature of myolysis and increased glycogen content dissociate them from the intrinsic adaptations to ischemia. These may be related to chronic elevations in preload but appear unlikely to contribute to chronic contractile dysfunction.
Key words: hibernating myocardium • stunned myocardium • myocardial ischemia • myofibrillar loss
This article has been cited by other articles:
 |
|
 |
|
  X. Zhang, X.-j. Liu, S. Hu, T. H. Schindler, Y. Tian, Z.-x. He, R. Gao, Q. Wu, H. Wei, J. W. Sayre, et al. Long-Term Survival of Patients with Viable and Nonviable Aneurysms Assessed by 99mTc-MIBI SPECT and 18F-FDG PET: A Comparative Study of Medical and Surgical Treatment J. Nucl. Med., August 1, 2008; 49(8): 1288 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Duncker and R. J. Bache Regulation of Coronary Blood Flow During Exercise Physiol Rev, July 1, 2008; 88(3): 1009 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Watanabe, H. Yaoita, K. Ogawa, M. Oikawa, K. Maehara, and Y. Maruyama Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol Cardiovasc Res, August 1, 2006; 71(3): 537 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Klocke Resting Blood Flow in Hypocontractile Myocardium: Resolving the Controversy Circulation, November 22, 2005; 112(21): 3222 - 3224. [Full Text] [PDF]
|
|
|
|
|
|
R. B. Driesen, G. D. Dispersyn, F. K. Verheyen, S. M. van den Eijnde, L. Hofstra, F. Thone, P. Dijkstra, W. Debie, M. Borgers, and F. C.S. Ramaekers Partial cell fusion: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts Cardiovasc Res, October 1, 2005; 68(1): 37 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ovchinnikov, G. Suzuki, J. M. Canty Jr., and J. A. Fallavollita Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1719 - H1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wiggers, H. E. Botker, V.L.J.L. Thijssen, M. Borgers, M.-H. Lenders, F.C.S. Ramaekers, G. Suzuki, B. Palka, J.A. Fallavollita, S.A. Thomas, et al. Letter Regarding Article by Thijssen et al, "Temporal and Spatial Variations in Structural Protein Expression During the Progression From Stunned to Hibernating Myocardium" * Response Circulation, June 7, 2005; 111(22): e378 - e379. [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, R. Schulz, and S. H. Rahimtoola Myocardial hibernation: a delicate balance Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H984 - H999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V.L.J.L. Thijssen, M. Borgers, M.-H. Lenders, F.C.S. Ramaekers, G. Suzuki, B. Palka, J.A. Fallavollita, S.A. Thomas, and J.M. Canty Jr Temporal and Spatial Variations in Structural Protein Expression During the Progression From Stunned to Hibernating Myocardium Circulation, November 23, 2004; 110(21): 3313 - 3321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. McFalls, M. Hou, R. J. Bache, A. Best, D. Marx, J. Sikora, and H. B. Ward Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1328 - H1334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Depre, S.-J. Kim, A. S. John, Y. Huang, O. E. Rimoldi, J. R. Pepper, G. D. Dreyfus, V. Gaussin, D. J. Pennell, D. E. Vatner, et al. Program of Cell Survival Underlying Human and Experimental Hibernating Myocardium Circ. Res., August 20, 2004; 95(4): 433 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Elsasser, A. M. Vogt, H. Nef, S. Kostin, H. Mollmann, W. Skwara, C. Bode, C. Hamm, and J. Schaper Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death J. Am. Coll. Cardiol., June 16, 2004; 43(12): 2191 - 2199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch and K. R. Sipido Myocardial Hibernation: A Double-Edged Sword Circ. Res., April 30, 2004; 94(8): 1005 - 1007. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Canty Jr, G. Suzuki, M. D. Banas, F. Verheyen, M. Borgers, and J. A. Fallavollita Hibernating Myocardium: Chronically Adapted to Ischemia but Vulnerable to Sudden Death Circ. Res., April 30, 2004; 94(8): 1142 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Kim, A. Peppas, S.-K. Hong, G. Yang, Y. Huang, G. Diaz, J. Sadoshima, D. E. Vatner, and S. F. Vatner Persistent Stunning Induces Myocardial Hibernation and Protection: Flow/Function and Metabolic Mechanisms Circ. Res., June 13, 2003; 92(11): 1233 - 1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch and R. Schulz Hibernating Myocardium: New Answers, Still More Questions! Circ. Res., November 15, 2002; 91(10): 863 - 865. [Full Text] [PDF]
|
|