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

Lucilla D. Monti, Sonia Allibardi, Pier Marco Piatti, Gianpietro Valsecchi, Sabrina Costa, Guido Pozza, Sergio Chierchia, Michele Samaja

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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 (PO 2 = 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 (NO x), the end products of nitric oxide, up to 6 μmol/min. Trimetazidine (1 μmol) further increased NO x 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3 50-3
Publication statusPublished - 2001


  • Nitric oxide

ASJC Scopus subject areas

  • Physiology


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