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 mu mol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (PO2 = 670 mmHg, pH 7.4, 37 degreesC) 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 mu mol/min. Trimetazidine (1 mu mol) 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 muM trimetazidine.

Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine / L. Monti, S. Allibardi, P. Piatti, G. Valsecchi, S. Costa, G. Pozza, S. Chierchia, M. Samaja. - In: AMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY. - ISSN 0363-6135. - 281:3(2001), pp. H1122-H1130.

Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine

M. Samaja
2001

Abstract

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 mu mol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (PO2 = 670 mmHg, pH 7.4, 37 degreesC) 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 mu mol/min. Trimetazidine (1 mu mol) 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 muM trimetazidine.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/181724
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