Triacsin C, a Fatty Acyl CoA Synthetase Inhibitor, Improves Cardiac Performance Following Global Ischemia

Abstract

The role of fatty acyl CoA synthetase (FACS) in ischemia/reperfusion (I/R) injury has not been well established. Our earlier studies showed that triacsin C, a selective FACS inhibitor, decreases endothelial nitric oxide synthase (eNOS) palmitoylation and increases nitric oxide (NO) in cultured human coronary endothelial cells. In the present study, we tested the hypothesis that triacsin C would reduce infarct size and improve post-reperfusion cardiac function by increasing vascular NO. In isolated rat hearts, triacsin C, given during the first 5 minutes of reperfusion, significantly reduced infarct size and attenuated cardiac dysfunction during reperfusion. N G -nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor, 50 µM) completely abolished the protective effects of triacsin C. In the ischemic hind limb model, triacsin C significantly increased intravascular NO concentration during reperfusion, an effect that was blocked by L-NAME or S-methyl-L-thiocitrulline (SMTC, a selective neuronal NOS inhibitor), but not by 1400W (a highly selective iNOS inhibitor). Lastly, triacsin C significantly reduced L-NAME induced leukocyte rolling, adhesion, and transmigration in rat mesenteric circulation, as measured by intravital microscopy. In summary, this study provides novel evidence showing that triacsin C reduces myocardial infarct size, attenuates loss of post-reperfusion cardiac function, increases intravascular NO concentration and inhibits leukocyte recruitment. These pharmacologic properties suggest that triacsin C may be useful as an adjunct to Am.

Apocynin Exerts Dose-Dependent Cardioprotective Effects by Attenuating Reactive Oxygen Species in Ischemia/Reperfusion

“…At the end of the experiment, the infarct area and area-at-risk (i.e. entire heart) was visualized and measured by treating the tissue with 1% 2,3,5-triphenyltetazolium (TTC), as previously described [25].…”

Nox2ds-Tat, A Peptide Inhibitor of NADPH Oxidase, Exerts Cardioprotective Effects by Attenuating Reactive Oxygen Species During Ischemia/Reperfusion Injury

“…The plasma was used as the vehicle for infusion of Nox2ds-tat. The hearts were rapidly excised and perfused via the Langendorff heart preparation [24]. The aorta was cannulated and retrograde perfused with modified Krebs' buffer containing: 17.0 mM dextrose, 120.0 mM NaCl, 25.0 mM NaHCO 3 , 2.5 mM CaCl 2 , 0.5 mM EDTA, 5.9 mM KCl, and 1.2 mM MgCl 2 .…”

Comparison of the Effects of Myristoylated and Transactivating Peptide (TAT) Conjugated Mitochondrial Fission Peptide Inhibitor (P110) in Myocardial Ischemia/Reperfusion (I/R) Injury

“…At the end of reperfusion, five heart slices (2 mm/slice) were subjected to 1% triphenyltetrazolium chloride (TTC) staining to detect non-viable (unstained) and viable (red stained) area. Infarct size was expressed as the percentage of non-viable tissue to the total tissue weight [6]. All data are presented as means ± SEM.…”