Sympathetic excitation contributes to clinical deterioration in systolic heart failure (HF). Significant inhibition of hypothalamic paraventricular nucleus (PVN) ERK1/2 signaling and a subsequent reduction of plasma norepinephrine (NE) levels in HF rats were achieved 2 weeks after a single subcutaneous injection of PD98059-loaded polymeric microparticles, without apparent adverse events, while blank microparticles had no effect. Similar reductions in plasma NE, a general indicator of sympathetic excitation, were previously achieved in HF rats by intracerebroventricular infusion of PD98059 or genetic knockdown of PVN ERK1/2 expression. This study presents a clinically feasible therapeutic approach to the central abnormalities contributing to HF progression.

中文翻译：

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可注射的微粒制剂可长期抑制心衰大鼠的下丘脑ERK1 / 2活性和交感神经兴奋性。

交感神经兴奋导致收缩性心力衰竭（HF）的临床恶化。皮下注射PD98059聚合物微粒一次皮下注射2周后，HF大鼠下丘脑室旁核（PVN）ERK1 / 2信号显着抑制，随后血浆去甲肾上腺素（NE）水平降低，无明显不良事件，而空白微粒没有作用。HF大鼠先前通过脑室内注入PD98059或通过基因敲低PVN ERK1 / 2表达，实现了血浆NE（交感神经兴奋的一般指标）的相似降低。这项研究提出了一种临床可行的治疗方法，用于治疗导致HF进展的中央异常。