A pacing-controlled protocol for frequency-diastolic relations distinguishes diastolic dysfunction specific to a mouse HFpEF model
A pacing-controlled protocol for frequency-diastolic relations distinguishes diastolic dysfunction specific to a mouse HFpEF model
复制标题
频率-舒张关系的起搏控制方案可区分小鼠 HFpEF 模型特有的舒张功能障碍
DOI：
10.1152/ajpheart.00241.2022
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发表时间：
2022
影响因子：
4.8
通讯作者：
Komuro Issei
中科院分区：
文献类型：
--
作者：
Numata Genri;Takimoto Eiki;Kariya Taro;Adachi Yusuke;Tokiwa Hiroyuki;Toyoda Masayuki;Mafune Ryo;Saito Yoshihiro;Nakamura Shun;Ueda Kazutaka;Ikeda Yuichi;Komuro Issei
射血分数保留性心力衰竭（HFpEF）以舒张功能障碍和运动能力不足为特征，是全球范围内日益严重的健康问题。HFpEF实验研究的一个主要困难是缺乏一致检测小鼠模型舒张功能障碍的方法。我们开发了一种起搏控制的压力-容积（PV）回路方案，用于评估小鼠在不同心率下的舒张功能，并测试该方案是否可以检测HFpEF模型特有的舒张功能障碍。通过高脂饮食（HFD）喂养伴随给予NG-硝基-L-精氨酸甲酯产生HFpEF模型，并且通过手术收缩横主动脉（TAC）产生压力超负荷肥大（PO）模型。通过腹腔注射伊伐布雷定，心率（HR）减慢至400次/min以下。使用插入食管的微型起搏导管，通过心房起搏，在HR从400次/min增加到700次/min时采集并分析PV环数据，并在对照、HFpEF和PO小鼠之间进行比较。在无起搏的基线时，PO或HFpEF模型均未检测到舒张异常。然而，频率-舒张的关系，揭示了显着的舒张功能障碍，具体的HFpEF模型;舒张时间常数（Tau）和舒张末期压力-容积关系（EDPVR）恶化的心率增加。左心室压力峰值正一阶导数（dP/dtmax）在HFpEF中仅在700次/分钟的高HR下显著低于对照组。起搏控制方案将是检测小鼠HFpEF模型特异性舒张功能障碍的可行且有效的方法。这是一种可行的和有效的方法，用于表征小鼠HFpEF模型中的舒张功能障碍，该模型的舒张功能障碍在静息条件下没有起搏可能难以检测。
Heart failure with preserved ejection fraction (HFpEF), characterized by diastolic dysfunction and insufficient exercise capacity, is a growing health problem worldwide. One major difficulty with experimental research on HFpEF is the lack of methods to consistently detect diastolic dysfunction in mouse models. We developed a pacing-controlled pressure-volume (PV) loop protocol for the assessment of diastolic function at different heart rates in mice and tested if the protocol could detect diastolic dysfunction specific to a HFpEF model. A HFpEF model was generated by high-fat diet (HFD) feeding with concomitantNG-nitro-l-arginine methyl ester administration, and a pressure-overload hypertrophy (PO) model was produced by surgical constriction of the transverse aorta (TAC). Heart rate (HR) was slowed below 400 beats/min by intraperitoneal injection of ivabradine. PV loop data were acquired and analyzed at HR incrementing from 400 to 700 beats/min via atrial pacing using a miniature pacing catheter inserted into the esophagus, and comparisons were made among control, HFpEF, and PO mice. At baseline without pacing, no diastolic abnormalities were detected in either PO or HFpEF models. Frequency-diastolic relations, however, revealed the significant diastolic impairment specific to the HFpEF model; both relaxation time constant (Tau) and end-diastolic pressure-volume relationship (EDPVR) were worsened as heart rate increased. Peak positive first derivative of left ventricular pressure (dP/dtmax) was significantly lower in HFpEF versus controls only at a high HR of 700 beats/min. A pacing-controlled protocol would be a feasible and potent method to detect diastolic dysfunction specific to a mouse HFpEF model.NEW & NOTEWORTHYWe developed a pacing-controlled PV loop protocol for the assessment of diastolic function at different heart rates in mice, which is a feasible and potent method for the characterization of diastolic dysfunction in a murine HFpEF model whose diastolic dysfunction might be difficult to be detected under resting conditions without pacing.