RESUMEN
Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatory effects. The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti-IL-6 antibodies (Abs) result in panantagonism. In a rat model of reperfused MI, sgp130Fc, but not anti-IL-6-Ab, attenuated neutrophil and macrophage infiltration into the myocardium, reduced infarct size, and preserved cardiac function 28 days after MI. These data demonstrate the efficacy of exclusive IL-6 trans-signaling blockade and support further investigation of sgp130Fc as a potential novel therapy in MI.
RESUMEN
With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac ischemia.
RESUMEN
No effective treatment is yet available to reduce infarct size and improve clinical outcomes after acute myocardial infarction by enhancing early reperfusion therapy using primary percutaneous coronary intervention. The study showed that Kyoto University Substance 121 (KUS121) reduced endoplasmic reticulum stress, maintained adenosine triphosphate levels, and ameliorated the infarct size in a murine cardiac ischemia and reperfusion injury model. The study confirmed the cardioprotective effect of KUS121 in a porcine ischemia and reperfusion injury model. These findings confirmed that KUS121 is a promising novel therapeutic agent for myocardial infarction in conjunction with primary percutaneous coronary intervention.
RESUMEN
Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague-Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (<1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.