|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2003; 41:1404-1407, doi:10.1016/S0735-1097(03)00164-5 © 2003 by the American College of Cardiology Foundation |
,*
* The Hatter Institute for Cardiology Research, MRC Inter-University Cape Heart Group, University of Cape Town Medical School, Cape Town, South Africa
The Hatter Institute for Cardiovascular Studies, UCL Hospitals & Medical School, London, United Kingdom
Manuscript received June 11, 2002; revised manuscript received September 23, 2002, accepted November 19, 2002.
* Reprint requests and correspondence: Prof. Derek M. Yellon, The Hatter Institute and Centre for Cardiology, University College London Hospitals & Medical School, Grafton Way, London WC1E 6DB United Kingdom.
hatter-institute{at}ucl.ac.uk
Reperfusion therapy has become a practical and effective strategy in the salvage of ischemic myocardium. The direct enhancement of cardiac cellular tolerance against ischemic and reperfusion injury should further improve patient outcome in acute coronary syndromes (ACS). This approach has been explored for many decades, and although we await mortality-weighted randomized clinical trials, the infusion of glucose-insulin-potassium (GIK) has shown promise in protecting post-infarct myocardium. The current dogma is that this cardioprotective effect of GIK acts via the modulation of cardiac and circulating metabolites to provide the heart with an optimal metabolic milieu to resist ischemia and reperfusion injury. This concept of metabolic modulation has gained favor in coronary heart disease, and its efficacy currently is being investigated in stable angina using the new class of partial fatty acid oxidation inhibitors, including trimetazidine and ranolazine. We contend that the mitogen insulin, itself, promotes tolerance against ischemic cell death via the activation of innate cell-survival pathways in the heart. To advance this viewpoint, we will present clinical data that support a dose-dependent effect of insulin’s beneficial action in the management of acute myocardial infarction. Furthermore, we present experimental data that identify cell-survival programs that are directly activated by the administration of insulin. Finally, as intravenous insulin therapy is both labor intensive and associated with metabolic perturbations, we propose that the development of pharmaco-therapeutic agents that target downstream cell-survival insulin-activated signaling molecules may be an alternate approach to promote cardioprotection during ACS.
| ||||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  R. Ascione, C.A. Rogers, C. Rajakaruna, and G.D. Angelini Inadequate Blood Glucose Control Is Associated With In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery Circulation, July 8, 2008; 118(2): 113 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Li, I. S. Ali, and R. W. Currie Insulin-induced myocardial protection in isolated ischemic rat hearts requires p38 MAPK phosphorylation of Hsp27 Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H74 - H87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, I. S. Ali, and R. W. Currie Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1709 - H1721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Koskenkari, P. K. Kaukoranta, K. T. Kiviluoma, M.J. P. Raatikainen, P. P. Ohtonen, and T. I. Ala-Kokko Metabolic and Hemodynamic Effects of High-Dose Insulin Treatment in Aortic Valve and Coronary Surgery Ann. Thorac. Surg., August 1, 2005; 80(2): 511 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Nikolaidis, A. Doverspike, T. Hentosz, L. Zourelias, Y.-T. Shen, D. Elahi, and R. P. Shannon Glucagon-Like Peptide-1 Limits Myocardial Stunning following Brief Coronary Occlusion and Reperfusion in Conscious Canines J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 303 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. LaDisa Jr., J. G. Krolikowski, P. S. Pagel, D. C. Warltier, and J. R. Kersten Cardioprotection by glucose-insulin-potassium: dependence on KATP channel opening and blood glucose concentration before ischemia Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H601 - H607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lee, J. Horowitz, and M. Frenneaux Metabolic manipulation in ischaemic heart disease, a novel approach to treatment Eur. Heart J., April 2, 2004; 25(8): 634 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Nikolaidis, S. Mankad, G. G. Sokos, G. Miske, A. Shah, D. Elahi, and R. P. Shannon Effects of Glucagon-Like Peptide-1 in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction After Successful Reperfusion Circulation, March 2, 2004; 109(8): 962 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.M Piper, Y Abdallah, and C Schafer The first minutes of reperfusion: a window of opportunity for cardioprotection Cardiovasc Res, February 15, 2004; 61(3): 365 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J Hausenloy and D. M Yellon New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway Cardiovasc Res, February 15, 2004; 61(3): 448 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Schnell, O. Schafer, S. Kleybrink, W. Doering, E. Standl, and W. Otter Intensification of Therapeutic Approaches Reduces Mortality in Diabetic Patients With Acute Myocardial Infarction: The Munich registry Diabetes Care, February 1, 2004; 27(2): 455 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Herzog How to Manage the Renal Patient with Coronary Heart Disease: The Agony and the Ecstasy of Opinion-Based Medicine J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2556 - 2572. [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
