Assessing structural and functional responses of murine hearts to acute and sustained β-adrenergic stimulation in vivo

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• 作者：Sarah-Lena Puhl ; ^{sarah_lena.puhl@kcl.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Kate L. Weeks ^{kate.weeks@kcl.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Antonella Ranieri ^{antonella.ranieri@kcl.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Metin Avkiran ^{metin.avkiran@kcl.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AW ; anterior wall ; β-AR ; β-adrenoceptor ; d ; end-diastolic ; DOB ; dobutamine ; EF ; ejection fraction ; FS ; fractional shortening ; HW ; heart weight ; i.p. ; intraperitoneal ; ISO ; isoprenaline ; IVS ; interventricular septum ; LV ; left ventricular ; LVAW ; left ventricular anterior wall ; LVID ; left ventricular internal diameter ; LVPW ; left ventricular posterior wall ; s ; end-systolic ; s.c ; subcutaneous ; TL ; tibia length ; vol ; volume
• 刊名：Journal of Pharmacological and Toxicological Methods
• 出版年：2016
• 出版时间：May-June 2016
• 年：2016
• 卷：79
• 期：Complete
• 页码：60-71
• 全文大小：1839 K

文摘

Given the importance of β-adrenoceptor signalling in regulating cardiac structure and function, robust protocols are required to assess potential alterations in such regulation in murine models in vivo.

Methods

Echocardiography was performed in naïve and stressed (isoprenaline; 30 μg/g/day s.c. for up to 14 days) mice, in the absence or presence of acute β-adrenergic stimulation (dobutamine 0.75 μg/g, i.p.). Controls received saline infusion and/or injection. Hearts were additionally analysed gravimetrically, histologically and biochemically.

Results

In naïve mice, acute β-adrenoceptor stimulation with dobutamine increased heart rate, left ventricular (LV) fractional shortening (LVFS), ejection fraction (LVEF) and wall thickness and decreased LV diameter (p < 0.05). In stressed mice, dobutamine failed to induce further inotropic and chronotropic responses. Furthermore, following dobutamine injection, these mice exhibited lower LVEF and LVFS at identical heart rates, relative to corresponding controls. Sustained isoprenaline infusion induced LV hypertrophy (increased heart weight, heart weight/body weight ratio, heart weight/tibia length ratio and LV wall thickness (p < 0.05)) by 3 days, with little further change at 14 days. In contrast, increases in LVEF and LVFS were seen only at 14 days (p < 0.05).

Discussion

We describe protocols for and illustrative data from the assessment of murine cardiac responses to acute and sustained β-adrenergic stimulation in vivo, which would be of value in determining the impact of genetic or pharmacological interventions on such responses. Additionally, our data indicate that acute dobutamine stimulation unmasks early signs of LV dysfunction in the remodelled heart, even at a stage when basal function is enhanced.