| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
2 The Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
3 Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA; The Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA
* To whom correspondence should be addressed. E-mail: jchatham{at}uab.edu.
Interventions that stimulate carbohydrate oxidation appear to be beneficial in the setting of myocardial ischemia or infarction. However, the mechanisms underlying this protective effect have not been defined, in part due to our limited understanding of substrate utilization under ischemic conditions. Therefore we used 1H and 13C NMR spectroscopy to investigate substrate oxidation and glycolytic rates in a global low flow model of myocardial ischemia. Isolated male Sprague-Dawley rat hearts were perfused for 30 min under conditions of normal flow (Control) and low flow ischemia (LFI, 0.3 ml/min) with insulin and 13C-labeled lactate, pyruvate, palmitate, and glucose at concentrations representative of the physiologic fed state. Despite a ~50-fold reduction in substrate delivery and oxygen consumption, oxidation of all exogenous substrates plus glycogen occurred during LFI. Oxidative metabolism accounted for 97% of the total calculated ATP production in the Control group and ~30% in the LFI group. For controls, lactate oxidation was the major source of ATP; however in LFI this shifted to a combination of oxidative and non-oxidative glycogen metabolism. Interestingly, in the LFI group, anaplerosis relative to citrate synthase increased 7-fold compared to the Control value. These results demonstrate the importance of oxidative energy metabolism for ATP production even during very low flow ischemia. We believe that the approach described here will be valuable for future investigations into the underlying mechanisms related to protective effect of increasing cardiac carbohydrate utilization and may ultimately lead to the identification of new therapeutic targets for the treatment of myocardial ischemia.
This article has been cited by other articles:
|
|
 |
|
  K. Carvajal, E. Zarrinpashneh, O. Szarszoi, F. Joubert, Y. Athea, P. Mateo, B. Gillet, S. Vaulont, B. Viollet, X. Bigard, et al. Dual cardiac contractile effects of the {alpha}2-AMPK deletion in low-flow ischemia and reperfusion Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3136 - H3147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Mallet, J. Sun, E. M. Knott, A. B. Sharma, and A. H. Olivencia-Yurvati Metabolic Cardioprotection by Pyruvate: Recent Progress Experimental Biology and Medicine, July 1, 2005; 230(7): 435 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wang, S. G. Lloyd, H. Zeng, A. Bonen, and J. C. Chatham Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2102 - H2110. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
