Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA; Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic University of Norway, 9037, Tromsø, Norway.
Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA.
Cryobiology. 2024 Sep;116:104927. doi: 10.1016/j.cryobiol.2024.104927. Epub 2024 Jun 25.
Victims of severe accidental hypothermia are frequently treated with catecholamines to counteract the hemodynamic instability associated with hypothermia-induced cardiac contractile dysfunction. However, we previously reported that the inotropic effects of epinephrine are diminished after hypothermia and rewarming (H/R) in an intact animal model. Thus, the goal of this study was to investigate the effects of Epi treatment on excitation-contraction coupling in isolated rat cardiomyocytes after H/R. In adult male rats, cardiomyocytes isolated from the left ventricle were electrically stimulated at 0.5 Hz and evoked cytosolic [Ca] and contractile responses (sarcomere length shortening) were measured. In initial experiments, the effects of varying concentrations of epinephrine on evoked cytosolic [Ca] and contractile responses at 37 °C were measured. In a second series of experiments, cardiomyocytes were cooled from 37 °C to 15 °C, maintained at 15 °C for 2 h, then rewarmed to 37 °C (H/R protocol). Immediately after rewarming, the effects of epinephrine treatment on evoked cytosolic [Ca] and contractile responses of cardiomyocytes were determined. At 37 °C, epinephrine treatment increased both cytosolic [Ca] and contractile responses of cardiomyocytes in a concentration-dependent manner peaking at 25-50 nM. The evoked contractile response of cardiomyocytes after H/R was reduced while the cytosolic [Ca] response was slightly elevated. The diminished contractile response of cardiomyocytes after H/R was not mitigated by epinephrine (25 nM) and epinephrine treatment reduced the exponential time decay constant (Tau), but did not increase the cytosolic [Ca] response. We conclude that epinephrine treatment does not mitigate H/R-induced contractile dysfunction in cardiomyocytes.
严重意外低体温症患者经常接受儿茶酚胺治疗，以对抗与低温诱导的心肌收缩功能障碍相关的血液动力学不稳定。然而，我们之前报道过，在完整的动物模型中，肾上腺素的变力作用在低温和复温（H/R）后会减弱。因此，本研究的目的是研究 Epi 处理对 H/R 后分离的大鼠心肌细胞兴奋-收缩偶联的影响。在成年雄性大鼠中，从左心室分离的心肌细胞以 0.5 Hz 的频率电刺激，测量胞质[Ca]和收缩反应（肌节长度缩短）。在最初的实验中，测量了不同浓度肾上腺素对 37°C 时胞质[Ca]和收缩反应的影响。在第二个系列的实验中，将心肌细胞从 37°C 冷却至 15°C，在 15°C 下维持 2 小时，然后复温至 37°C（H/R 方案）。复温后立即测定肾上腺素处理对心肌细胞胞质[Ca]和收缩反应的影响。在 37°C 时，肾上腺素处理以浓度依赖性方式增加了胞质[Ca]和心肌细胞的收缩反应，峰值在 25-50 nM。H/R 后心肌细胞的诱发收缩反应降低，而胞质[Ca]反应略有升高。H/R 后心肌细胞收缩反应减弱不能被肾上腺素（25 nM）缓解，肾上腺素处理降低指数时间衰减常数（Tau），但不增加胞质[Ca]反应。我们得出结论，肾上腺素处理不能减轻心肌细胞的 H/R 诱导的收缩功能障碍。
