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Background <p>The sigma-1 receptor (Sig-1R) plays diverse roles in regulating Endoplasmic Reticulum (ER) stress, calcium handling, and ion channel activity under pathological conditions, offering cardioprotective effects in pressure overload-induced dysfunction. However, its role in post-myocardial ischemia damage remains unclear. This study evaluated the cardioprotective effects of Sig-1R activation by fluvoxamine following myocardial ischemia in rats.</p> Method and Results <p>Wistar rats underwent 20&#xa0;min of coronary artery occlusion followed by reperfusion. Rats received either saline (control) or fluvoxamine for two weeks. ECG-gated SPECT with <sup>99m</sup>Tc-MIBI was performed on days 1, 14, and 28 post-reperfusion to measure the end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), and summed rest score (SRS). Autoradiography and histological analyses were performed on day 29. Fluvoxamine significantly improved LVEF after two weeks (D14–D1: 6 ± 7, <i>p</i> = 0.03), with the improvement persisting to the 28th day (8 ± 5, <i>p</i> &lt; 0.01). Autoradiography revealed a smaller non-salvaged area (0.15 ± 0.19 vs. 0.42 ± 0.32, <i>p</i> &lt; 0.05) and more salvaged myocardium (0.33 ± 0.13 vs. 0.14 ± 0.14, <i>p</i> &lt; 0.05) in the fluvoxamine group. Histology showed less fibrosis (0.06 ± 0.05 vs. 0.11 ± 0.08, <i>p</i> &lt; 0.05) and reduced macrophage infiltration (0.08 ± 0.05 vs. 0.16 ± 0.08, <i>p</i> &lt; 0.001) with fluvoxamine.</p> Conclusions <p>Sig-1R stimulation by fluvoxamine suppresses LV remodelling and enhances LVEF recovery post-ischemia, suggesting its potential as a novel cardioprotective strategy.</p>

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Positive Protective Effects of Sigma-1 Receptor Stimulation with Fluvoxamine after Myocardial Ischemia and Reperfusion in Rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月3日

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  • Xue Zhang,
  • Hiroshi Wakabayashi,
  • Hiroshi Mori,
  • Tomo Hiromasa,
  • Zhuoqing Chen,
  • Takashi Kozaka,
  • Kazuma Ogawa,
  • Seigo Kinuya,
  • Junichi Taki

摘要

Background

The sigma-1 receptor (Sig-1R) plays diverse roles in regulating Endoplasmic Reticulum (ER) stress, calcium handling, and ion channel activity under pathological conditions, offering cardioprotective effects in pressure overload-induced dysfunction. However, its role in post-myocardial ischemia damage remains unclear. This study evaluated the cardioprotective effects of Sig-1R activation by fluvoxamine following myocardial ischemia in rats.

Method and Results

Wistar rats underwent 20 min of coronary artery occlusion followed by reperfusion. Rats received either saline (control) or fluvoxamine for two weeks. ECG-gated SPECT with 99mTc-MIBI was performed on days 1, 14, and 28 post-reperfusion to measure the end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), and summed rest score (SRS). Autoradiography and histological analyses were performed on day 29. Fluvoxamine significantly improved LVEF after two weeks (D14–D1: 6 ± 7, p = 0.03), with the improvement persisting to the 28th day (8 ± 5, p < 0.01). Autoradiography revealed a smaller non-salvaged area (0.15 ± 0.19 vs. 0.42 ± 0.32, p < 0.05) and more salvaged myocardium (0.33 ± 0.13 vs. 0.14 ± 0.14, p < 0.05) in the fluvoxamine group. Histology showed less fibrosis (0.06 ± 0.05 vs. 0.11 ± 0.08, p < 0.05) and reduced macrophage infiltration (0.08 ± 0.05 vs. 0.16 ± 0.08, p < 0.001) with fluvoxamine.

Conclusions

Sig-1R stimulation by fluvoxamine suppresses LV remodelling and enhances LVEF recovery post-ischemia, suggesting its potential as a novel cardioprotective strategy.