Abstract | OBJECTIVE: Metabolic interventions that promote glucose use during ischemia have been shown to protect the myocardium and improve functional recovery on reperfusion. In this study we evaluated if cardioprotection can be accomplished by inhibiting fatty acid uptake, which would be expected to increase glycolytic metabolism. METHODS: RESULTS: Ischemic injury, as assessed by creatine kinase release, was diminished in hearts perfused with DIDS (334+/-72 in DIDS vs. 565+/-314 IU/g dry wt in controls, P<0.04). Increases in LVEDP during ischemia were attenuated (8+/-3 mmHg in DIDS vs. 15+/-18 mmHg in controls, P<0.03) and the % recovery of LV function with reperfusion was enhanced in DIDS-treated hearts (78+/-10% of baseline in DIDS vs. 62+/-19% of baseline in controls, P<0.04). These beneficial effects of DIDS were associated with increased glucose metabolism and ATP content during ischemia and reperfusion. Furthermore, treatment with DIDS lowered the accumulation of long chain acyl carnitines. CONCLUSIONS: This study demonstrates that DIDS protects ischemic myocardium, and is associated with inhibition of fatty acid uptake, improved glucose metabolism, and enhanced functional recovery on reperfusion. The data presented here suggest a potential role for therapeutic agents that lower fatty acid uptake as a metabolic adjunct in the treatment of myocardial ischemia.
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Authors | R Ramasamy, Y Hwang, S Bakr, S R Bergmann |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 51
Issue 2
Pg. 275-82
(Aug 01 2001)
ISSN: 0008-6363 [Print] England |
PMID | 11470467
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anion Exchange Protein 1, Erythrocyte
- Fatty Acids
- Phospholipids
- Triglycerides
- acylcarnitine
- Phosphocreatine
- Adenosine Triphosphate
- Glucose
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
- Carnitine
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Topics |
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
(therapeutic use)
- Adenosine Triphosphate
(analysis)
- Animals
- Anion Exchange Protein 1, Erythrocyte
(antagonists & inhibitors)
- Carnitine
(analogs & derivatives, analysis)
- Fatty Acids
(analysis, metabolism)
- Glucose
(metabolism)
- Myocardial Ischemia
(metabolism)
- Myocardial Reperfusion
- Myocardium
(chemistry, metabolism)
- Oxidation-Reduction
- Perfusion
- Phosphocreatine
(analysis)
- Phospholipids
(metabolism)
- Rats
- Triglycerides
(metabolism)
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