European Heart Journal Advance Access originally published online on June 30, 2007
European Heart Journal 2007 28(22):2792-2798; doi:10.1093/eurheartj/ehm241
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Multi-parameter in vivo cardiac magnetic resonance imaging demonstrates normal perfusion reserve despite severely attenuated ß-adrenergic functional response in neuronal nitric oxide synthase knockout mice
1 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA
2 Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA
3 Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
4 Cardiovascular Research Center, University of Virginia Charlottesville, VA 22908, USA
5 Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand
Received 29 September 2006; revised 14 May 2007; accepted 23 May 2007; online publish-ahead-of-print 30 June 2007.
* Corresponding author. Tel: +1 434 982 0563; fax: +1 434 924 9435. E-mail address: fredepstein{at}virginia.edu
Aims: The role of neuronal nitric oxide synthase (nNOS) in regulating contractile function remains controversial, and in regulating myocardial perfusion is uninvestigated. We used magnetic resonance imaging (MRI) to phenotype nNOS–/– and wild-type (WT) mice regarding left ventricular (LV) structure, baseline function, ß-adrenergic responsiveness, and perfusion reserve.
Methods and results: Cine MRI showed higher LV mass to end-diastolic volume ratio (2.3 ± 0.2 mg/µL nNOS–/– vs. 1.7 ± 0.1 mg/µL WT; P=0.032) and LV ejection fraction (64.9 ± 2.1% nNOS–/– vs. 55.8 ± 1.1% WT; P = 0.003) in nNOS–/–. Myocardial tagging demonstrated similar baseline systolic circumferential strain (Ecc) in nNOS–/– and WT. With dobutamine, the normal change in Ecc was nearly absent in nNOS–/– (–0.5 ± 0.3% nNOS–/– vs. –2.2 ± 0.3% WT; P = 0.001), and the systolic strain rate (dEcc/dt) response to dobutamine seen in WT was reduced in nNOS–/– (–29 ± 13%/s nNOS–/– vs. –106±16%/s WT; P = 0.001). Diastolic strain rate increased significantly with dobutamine only in WT. Arterial spin labelling showed that baseline perfusion and perfusion reserve with either dobutamine or an adenosine receptor agonist are normal in nNOS–/–.
Conclusion: MRI provides non-invasive in vivo evidence that nNOS does not play a role in basal contractile function or myocardial perfusion, but is required for increasing cardiac inotropy and lusitropy upon ß-adrenergic stimulation.
Key Words: Neuronal nitric oxide synthase • Cardiac function • Heart • MRI • Adrenergic stimulation • Myocardial tagging