Reply: Tolerating Large Preclinical Models of HFpEF But Without the Intolerance?
Reply: Tolerating Large Preclinical Models of HFpEF But Without the Intolerance?
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DOI：
10.1016/j.jacbts.2021.03.004
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Goodchild TT
中科院分区：
文献类型：
--
作者：
Sharp TE;Lefer DJ;Goodchild TT
Sharp等人(1)报道了一种新的大型动物心力衰竭模型，通过长期饮食和盐皮质激素的使用，使用了一种已知易患肥胖症、代谢综合征和动脉粥样硬化的健康小型猪，建立了射血分数保留(HFpEF)的大动物模型。我们要祝贺作者试图实现从较小的临床前实验模型到较大的临床前实验模型的复杂过渡，这是改进HFpEF治疗方法迫切需要的重要一步。作者的结论是，他们的模型准确而恰当地概括了人类HFpEF条件下所有共病的复杂性特征。然而，奇怪的是，正如作者在导言中所说的那样，所有患者都表现出典型的左心室充盈率升高，尽管保留了LVEF并伴有运动耐受。然而，似乎没有提供任何数据来说明与健康对照组相比，小型猪是否出现了运动不耐受的迹象。鉴于HFpEF患者的必要条件是运动不耐受，人们不禁要问，目前的小型猪模型是否解决了这一重要问题。如美国心脏病学会基金会/美国心脏协会临床指南所示，以心脏和非心脏生理储备受损为特征的运动不耐受是HFpEF的基本特征。此外，运动不耐受与HFpEF的外周改变密切相关，包括骨骼肌、外周血流和血管异常(2-5)。在没有数据证实运动限制的存在和严重程度，以及外周限制的继发性发展的情况下，我们应该停下来仔细思考，这个模型实际上是否真实地反映了HFpEF患者，或者仅仅反映了几乎但不完全反映。
Sharp et al.(1) report a novel large animal model of heart failure with preserved ejection fraction (HFpEF) induced through long-term dietary and mineralocorticoid administration, using a wellestablished minipig breed with known susceptibilities to obesity, metabolic syndrome, and atherosclerosis. We would like to congratulate the authors on attempting to make the complex transition from smaller to larger pre-clinical experimental models, an important step that is urgently required to progress therapeutic treatments in HFpEF. The authors concluded that their model accurately and appropriately recapitulated all the comorbidity complexities characteristic of the human HFpEF condition. Curiously, however, as stated by the authors in the introduction, all patients typically demonstrate elevated left ventricular (LV) filling rates, despite preserved LVEF alongside exercise intolerance. However, it appears no data were provided as to whether the minipigs developed signs of exercise intolerance compared to healthy controls. Given the sine qua non of patients with HFpEF is exercise intolerance, one begs the question of whether this current minipig model addresses this important point. Exercise intolerance, characterized by impairments to both cardiac and noncardiac physiological reserves, is a cardinal feature of HFpEF, as shown in the American College of Cardiology Foundation/American Heart Association clinical guidelines. Moreover, exercise intolerance is closely linked to peripheral alterations in HFpEF that includes skeletal muscle, peripheral blood flow, and vascular abnormalities(2–5). Without data corroborating the presence and severity of exercise limitation, as well as secondary development of peripheral limitations, we should pause to carefully reflect whether this model does in fact closely reflect the patient with HFpEF or simply reflect an almost but not quite.
影响因子：
37.8
作者：
Ho JE;Redfield MM;Lewis GD;Paulus WJ;Lam CSP
通讯作者：
Lam CSP
影响因子：
18.2
作者：
Pieske, Burkert;Tschoepe, Carsten;Filippatos, Gerasimos
通讯作者：
Filippatos, Gerasimos