Cardiac and coronary function in the Langendorff-perfused mouse heart model

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Title Cardiac and coronary function in the Langendorff-perfused mouse heart model
Author Reichelt, Melissa Elizabeth; Willems, Laura; Hack, Benjamin A.; Peart, Jason Nigel John; Headrick, John Patrick
Journal Name Experimental Physiology
Year Published 2009
Place of publication UK
Publisher Wiley-Blackwell Publishing Ltd
Abstract The Langendorff mouse heart model is widely employed in studies of myocardial function and responses to injury (e.g. ischaemia). Nonetheless, marked variability exists in its preparation and functional properties. We examined the impact of early growth (8, 16, 20 and 24 weeks), sex, perfusion fluid [Ca2+] and pacing rate on contractile function and responses to 20 min ischaemia followed by 45 min reperfusion. We also assessed the impact of strain, and tested the utility of the model in studying coronary function. Under normoxic conditions, hearts from 8-week-old male C57BL/6 mice (2 mm free perfusate [Ca2+], 420 beats min–1) exhibited 145 ± 2 mmHg left ventricular developed pressure (LVDP). Force development declined by ∼15% (126 ± 5 mmHg) with a reduction in free [Ca2+] to 1.35 mm, and by 25% (108 ± 3 mmHg) with increased pacing to 600 beats min–1. While elevated heart rate failed to modify ischaemic outcome, the lower [Ca2+] significantly improved contractile recovery (by >30%). We detected minimal sex-dependent differences in normoxic function between 8 and 24 weeks, although age modified contractile function in males (increased LVDP at 24 versus 8 weeks) but not females. Both male and female hearts exhibited age-related reductions in ischaemic tolerance, with a significant decline in recovery evident at 16 weeks in males and later, at 20–24 weeks, in females (versus recoveries in hearts at 8 weeks). Strain also modified tolerance to ischaemia, with similar responses in hearts from C57BL/6, 129/sv, Quackenbush Swiss and FVBN mice, but substantially greater tolerance in BALB/c hearts. In terms of vascular function, baseline coronary flow (20–25 ml min−1 g−1) was 50–60% of maximally dilated flows, and coronary reactive and functional hyperaemic responses were pronounced (up to 4-fold elevations in flow in hearts lacking ventricular balloons). These data indicate that attention to age (and sex) of mice will reduce variability in contractile function and ischaemic responses. Even small differences in perfusion fluid [Ca2+] also significantly modify tolerance to ischaemia (whereas modest shifts in heart rate do not impact). Ischaemic responses are additionally strain dependent, with BALB/c hearts displaying greatest intrinsic tolerance. Finally, the model is applicable to the study of vascular reactivity, providing large responses and excellent reproducibility.
Peer Reviewed Yes
Published Yes
Publisher URI http://ep.physoc.org/
Alternative URI http://dx.doi.org/10.1113/expphysiol.2008.043554
Volume 94
Issue Number 1
Page from 54
Page to 70
ISSN 0958-0670
Date Accessioned 2008-10-01
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Animal Physiology-Systems
URI http://hdl.handle.net/10072/26144
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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