Pironti Gianluigi
Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Front Cardiovasc Med. 2023 Aug 7;10:1228789. doi: 10.3389/fcvm.2023.1228789. eCollection 2023.
Cardiovascular diseases (CVD) are still the leading cause of death worldwide. The improved survival of patients with comorbidities such as type 2 diabetes, hypertension, obesity together with the extension of life expectancy contributes to raise the prevalence of CVD in the increasingly aged society. Therefore, a translational research platform that enables precise evaluation of cardiovascular function in healthy and disease condition and assess the efficacy of novel pharmacological treatments, could implement basic science and contribute to reduce CVD burden. Heart failure is a deadly syndrome characterized by the inability of the heart to meet the oxygen demands of the body (unless there is a compensatory increased of filling pressure) and can manifest either with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The development and progression of HFrEF is mostly attributable to impaired contractile performance (systole), while in HFpEF the main problem resides in decreased ability of left ventricle to relax and allow the blood filling (diastole). Murine preclinical models have been broadly used in research to understand pathophysiologic mechanisms of heart failure and test the efficacy of novel therapies. Several methods have been employed to characterise cardiac systolic and diastolic function including Pressure Volume (PV) loop hemodynamic analysis, echocardiography and Magnetic Resonance Imaging (MRI). The choice of one methodology or another depends on many aspects including budget available, skills of the operator and design of the study. The aim of this review is to discuss the importance of several methodologies that are commonly used to characterise the cardiovascular phenotype of preclinical models of heart failure highlighting advantages and limitation of each procedure. Although it requires highly skilled operators for execution, PV loop analysis represents the "gold standard" methodology that enables the assessment of left ventricular performance also independently of vascular loading conditions and heart rate, which conferee a really high physiologic importance to this procedure.
心血管疾病(CVD)仍是全球主要的死亡原因。2型糖尿病、高血压、肥胖等合并症患者生存率的提高以及预期寿命的延长,促使心血管疾病在老龄化社会中的患病率不断上升。因此,一个能够在健康和疾病状态下精确评估心血管功能,并评估新型药物治疗效果的转化研究平台,可推动基础科学发展并有助于减轻心血管疾病负担。心力衰竭是一种致命综合征,其特征是心脏无法满足身体的氧气需求(除非充盈压代偿性升高),可表现为射血分数降低(HFrEF)或射血分数保留(HFpEF)。HFrEF的发生和发展主要归因于收缩功能受损(收缩期),而在HFpEF中,主要问题在于左心室舒张和允许血液充盈的能力下降(舒张期)。小鼠临床前模型已广泛应用于研究,以了解心力衰竭病理生理机制并测试新型疗法的疗效。已采用多种方法来表征心脏的收缩和舒张功能,包括压力-容积(PV)环血流动力学分析、超声心动图和磁共振成像(MRI)。选择哪种方法取决于许多因素,包括可用预算、操作人员的技能和研究设计。本综述的目的是讨论几种常用于表征心力衰竭临床前模型心血管表型的方法的重要性,突出每种方法的优点和局限性。尽管PV环分析需要高技能操作人员来执行,但它是“金标准”方法,能够独立于血管负荷条件和心率评估左心室功能,这赋予了该方法极高的生理重要性。