| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Divisione di Medicina, 2 Unita' di Malattie Metaboliche, Divisione di Medicina, 3 Cattedra di Clinica Medica Generale e Terapia Medica, Universita' Vita-Salute, 4 Dipartimento di Cardiologia, Istituto di Ricovero e Cura a Carattere Scientifico, Hospital San Raffaele, 20132 Milan; and 5 Dipartimento di Medicina, Chirurgia ed Odontoiatria-DiMCO, Ospedale San Paolo, University of Milan, Milan I-20090, Italy
There is growing evidence that hypertriglyceridemia exacerbates ischemic injury. We tested the hypothesis that triglycerides impair myocardial recovery from low-flow ischemia in an ex vivo model and that such an effect is related to endothelin-1. Hyperglycemic (glucose concentration = 12 mmol/l) and hyperinsulinemic (insulin concentration = 1.2 µmol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (PO2 = 670 mmHg, pH 7.4, 37°C) added with increasing triglycerides (0, 1,000, 2,000, and 4,000 mg/dl, n = 6-9 rats/group). Hearts were exposed to 60 min of low-flow ischemia (10% of basal coronary flow), followed by 30 min of reperfusion. We found that increasing triglycerides impaired both the diastolic (P < 0.005) and systolic (P < 0.02) recovery. The release of endothelin-1 during reperfusion increased linearly with triglyceride concentration (P = 0.0009). Elevated triglycerides also increased the release of nitrite and nitrate (NOx), the end products of nitric oxide, up to 6 µmol/min. Trimetazidine (1 µmol) further increased NOx release, blunted endothelin-1 release, and protected myocardial function during recovery. We conclude that high triglyceride levels impair myocardial recovery after low-flow ischemia in association with endothelin-1 release. The endothelium-mediated effect of triglycerides on both contractile recovery and endothelin-1 release is prevented by 1 µM trimetazidine.
nitric oxide
This article has been cited by other articles:
|
|
 |
|
  S. Tamareille, H. Achour, J. Amirian, P. Felli, R. J. Bick, B. Poindexter, Y. J. Geng, W. H. Barry, and R. W. Smalling Left ventricular unloading before reperfusion reduces endothelin-1 release and calcium overload in porcine myocardial infarction. J. Thorac. Cardiovasc. Surg., August 1, 2008; 136(2): 343 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Monti, E. Setola, G. Fragasso, R. P. Camisasca, P. Lucotti, E. Galluccio, A. Origgi, A. Margonato, and P. Piatti Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E54 - E59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Monti, C. Landoni, E. Setola, E. Galluccio, P. Lucotti, E. P. Sandoli, A. Origgi, G. Lucignani, P. Piatti, and F. Fazio Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1225 - H1231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Milano, A. F. Corno, S. Lippa, L. K. von Segesser, and M. Samaja Chronic and Intermittent Hypoxia Induce Different Degrees of Myocardial Tolerance to Hypoxia-Induced Dysfunction Experimental Biology and Medicine, June 1, 2002; 227(6): 389 - 397. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
