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

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Abstract

INTRODUCTION: 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; 30μg/g/days.c. for up to 14days) mice, in the absence or presence of acute β-adrenergic stimulation (dobutamine 0.75μg/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 3days, with little further change at 14days. In contrast, increases in LVEF and LVFS were seen only at 14days (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.

Original languageEnglish
Pages (from-to)60-71
JournalJournal of pharmacological and toxicological methods
Volume79
Early online date4 Feb 2016
DOIs
Publication statusPublished - May 2016

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