salvianolic-acid-a and Ventricular-Dysfunction--Left

Salvianolic acid A (Sal A), the water-soluble component from the root of the Salvia miltiorrhiza plant, possesses antioxidant, antiproliferative, and antiplatelet properties. However, whether it plays a role in the protection against ischemia-reperfusion (I/R) injury in rat hearts has yet to be elucidated. In the present study, we tested cell viability, shortening amplitude, necrosis, apoptosis, and the expression levels of Akt, phosphorylated Akt, Bcl-2, Bax, and caspase-3 after 3-hour simulated ischemia and 2- or 6-hour simulated reperfusion in cardiomyocytes. We further observed the contractile function and infarct size in isolated hearts after they were subjected to global 30-minute ischemia and 120-minute reperfusion. Pretreatment with Sal A markedly increased cell viability and shortening amplitude while reducing evidence of necrosis and apoptosis in the cells. In addition, the expression of Bcl-2 was upregulated and Bax was downregulated, thereby increasing the Bcl-2/Bax ratio. Sal A inhibited the activation of caspase-3 as well. The results also showed that Sal A significantly increased phosphorylation of Akt and that this phosphorylation can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor. Furthermore, Sal A improved I/R-induced myocardial contractile function and reduced infarct size. In summary, our results showed that Sal A prevents I/R-induced myocardial damage by reducing necrosis and apoptosis in isolated rat hearts and cardiomyocytes.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caffeic Acids; Cardiotonic Agents; Caspase 3; Cell Shape; Cell Survival; Heart; Heart Rate; In Vitro Techniques; L-Lactate Dehydrogenase; Lactates; Male; Myocardial Contraction; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Necrosis; Perfusion; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ventricular Dysfunction, Left