Walsh-Wilkinson Elisabeth, Arsenault Marie, Couet Jacques
Universite Laval, Groupe de recherche sur les valvulopathies, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Quebec, Quebec, Canada.
PeerJ. 2021 Mar 12;9:e11085. doi: 10.7717/peerj.11085. eCollection 2021.
We studied by conventional and speckle-tracking echocardiography, the response of the left ventricle (LV) to a three-week continuous infusion of isoproterenol (Iso), a non-specific beta-adrenergic receptor agonist in male and female C57Bl6/J mice. Before and after Iso (30 mg/kg/day), we characterized LV morphology and function as well as global and segmental strain. We observed that Iso reduced LV ejection in both male (-8.7%) and female (-14.7%) mice. Several diastolic function parameters were negatively regulated in males and females such as E/A, E/E', isovolumetric relaxation time. Global longitudinal (GLS) and circumferential (GCS) strains were reduced by Iso in both sexes, GLS by 31% and GCS by about 20%. For the segmental LV analysis, we measured strain, strain rate, reverse strain rate, peak speckle displacement and peak speckle velocity in the parasternal long axis. We observed that radial strain of the LV posterior segments were more severely modulated by Iso than those of the anterior wall in males. In females, on the other hand, both posterior and anterior wall segments were negatively impacted by Iso. Longitudinal strain showed similar results to the radial strain for both sexes. Strain rate, on the other hand, was only moderately changed by Iso. Reverse strain rate measurements (an index of diastolic function) showed that posterior LV segments were negatively regulated by Iso. We then studied the animals 5 and 17 weeks after Iso treatment. Compared to control mice, LV dilation was still present in males. Ejection fraction was decreased in mice of both sex compared to control animals. Diastolic function parameters, on the other hand, were back to normal. Taken together, our study indicates that segmental strain analysis can identify LV regions that are more negatively affected by a cardiotoxic agent such as Iso. In addition, cessation of Iso was not accompanied with a complete restoration of cardiac function after four months.
我们通过传统超声心动图和斑点追踪超声心动图，研究了雄性和雌性C57Bl6/J小鼠的左心室（LV）对为期三周的异丙肾上腺素（Iso）持续输注的反应，Iso是一种非特异性β-肾上腺素能受体激动剂。在给予Iso（30 mg/kg/天）之前和之后，我们对左心室的形态和功能以及整体和节段应变进行了表征。我们观察到，Iso降低了雄性（-8.7%）和雌性（-14.7%）小鼠的左心室射血。男性和女性的几个舒张功能参数受到负调节，如E/A、E/E'、等容舒张时间。Iso使两性的整体纵向（GLS）和圆周（GCS）应变均降低，GLS降低31%，GCS降低约20%。对于左心室节段分析，我们测量了胸骨旁长轴的应变、应变率、反向应变率、峰值斑点位移和峰值斑点速度。我们观察到，雄性小鼠左心室后壁节段的径向应变比前壁受Iso的调节更严重。另一方面，在雌性小鼠中，后壁和前壁节段均受到Iso的负面影响。两性的纵向应变与径向应变结果相似。另一方面，应变率仅受到Iso的中度改变。反向应变率测量（舒张功能指标）显示，左心室后壁节段受到Iso的负调节。然后，我们在Iso治疗后5周和17周对动物进行了研究。与对照小鼠相比，雄性小鼠仍存在左心室扩张。与对照动物相比，两性小鼠的射血分数均降低。另一方面，舒张功能参数恢复正常。综上所述，我们的研究表明，节段应变分析可以识别受心脏毒性药物如Iso负面影响更大的左心室区域。此外，停止使用Iso四个月后，心脏功能并未完全恢复。
