Abstract |
The study was designed to characterise the influence of a novel acyl-CoA:cholesterol acyltransferase inhibitor, VULM 1457, on the severity of myocardial ischaemia- reperfusion injury in a model of diabetes mellitus and hypercholesterolaemia induced by co-administration of streptozotocin and a high fat- cholesterol diet. We used Langendorff-perfused rat hearts to measure the size of myocardial infarction after 30 min of regional ischaemia, followed by a 2-h reperfusion period, and open-chest rats were exposed to 6 min of ischaemia and 10 min of reperfusion to analyse ventricular arrhythmias. In addition to the high fat- cholesterol diet, VULM 1457 was administered to the diabetic-hypercholesterolaemic rats for 5 days. Decreased plasma and liver cholesterol levels and a significantly reduced occurrence of ventricular fibrillation (29% vs. 100%, P<0.01), determined via the mean number and duration of episodes (0.6+/-0.4 and 2.1+/-1.4 s vs. 2.8+/-0.8 and 53.5+/-14.4 s in diabetic-hypercholesterolaemic rats, both P<0.01), were observed in these animals. Lethal ventricular fibrillation was suppressed, and arrhythmia severity was also significantly decreased in these animals as compared to the non-treated animals (2.9+/-0.6 vs. 4.9+/-0.2; P<0.05). A smaller infarct size, normalised to the size of area at risk, was observed in the treated diabetic-hypercholesterolaemic group as compared to the non-treated group (16.3+/-1.9% vs. 37.3+/-3.1%; P<0.01). Aside from remarkable hypolipidaemic activity, VULM 1457 improved the overall myocardial ischaemia- reperfusion injury outcomes in the diabetic-hypercholesterolaemic rats by suppressing arrhythmogenesis as well as by reducing myocardial necrosis.
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Authors | Adriana Adameová, Tána Ravingerová, Pavel Svec, Viera Faberová, Magdaléna Kuzelová |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 576
Issue 1-3
Pg. 114-21
(Dec 08 2007)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 17764671
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Arrhythmia Agents
- Cholesterol, Dietary
- Hypolipidemic Agents
- VULM 1457
- Sterol O-Acyltransferase
- Clofibrate
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Topics |
- Animals
- Anti-Arrhythmia Agents
(pharmacology)
- Cholesterol, Dietary
(administration & dosage)
- Clofibrate
(analogs & derivatives, pharmacology)
- Diabetes Mellitus, Experimental
(complications, drug therapy, physiopathology)
- Hypercholesterolemia
(complications, drug therapy, etiology, physiopathology)
- Hypolipidemic Agents
(pharmacology)
- Male
- Myocardial Infarction
(drug therapy, etiology, physiopathology)
- Rats
- Rats, Wistar
- Reperfusion Injury
(prevention & control)
- Sterol O-Acyltransferase
(antagonists & inhibitors)
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