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Post-infarct morphine treatment mitigates left ventricular remodeling and dysfunction in a rat model of ischemia-reperfusion
Ist Teil von
European journal of pharmacology, 2019-03, Vol.847, p.61-71
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals Complete
Beschreibungen/Notizen
Following myocardial infarction, the heart undergoes a series of dramatic compensations which may later form a maladaptive picture characterized by ventricular dilation and pump failure. Among several opioid agents, morphine has been shown to confer protection against reperfusion injury and infarct size. Here, we sought to study the cardioprotective effect of post-infarct morphine treatment against left ventricular adverse remodeling. We induced myocardial infarction in male Sprague - Dawley rats by ligating left anterior descending artery and then, treated these animals with three different doses of morphine −0.3, 3 and 10 mg/kg (i.p.). The echocardiographic evaluation depicted improved cardiac performance and lesser chamber dilation in the animals that had received 3 mg/kg of morphine. Next, we studied the effect of 3 mg/kg morphine administration on left ventricular hemodynamics, infarct size, tissue architecture, changes in lung and heart weight, circulating TNF-α level and post-MI mRNA expression of collagen-1, collagen-3, TGF-β, TNF-α, MMP-2 and MMP-9. Five-day morphine administration markedly improved LV function, and also reduced infarct size, myocyte hypertrophy, fibrosis, index of infarct expansion, heart weight and serum TNF-α level. Moreover, morphine alleviated MI-induced increase in wet and dry lung weight. Morphine also altered the mRNA expression of fibrosis-related genes, TNF-α, MMP-2 and MMP-9. In conclusion, post-infarct morphine treatment can mitigate adverse remodeling and cardiac dysfunction after MI. Beside analgesic effect, we may be able to harvest benefits from the antifibrotic and anti-remodeling action of morphine in patients with the acute coronary syndrome.
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