Abstract
SUMMARYThe physiology of the Drosophila melanogaster cardiovascular system remains poorly characterized compared with its vertebrate counterparts. Basic measures of physiological performance remain unknown. It also is unclear whether subtle physiological defects observed in the human cardiovascular system can be reproduced in D. melanogaster. Here we characterize the cardiovascular physiology of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and optical coherence tomography. The heart has vigorous pulsatile contractions that drive intracardiac, aortic and extracellular-extravascular hemolymph flow. Several physiological measures, including weight-adjusted cardiac output, body-length-adjusted aortic velocities and intracardiac shear forces, are similar to those in the closed vertebrate cardiovascular systems, including that of humans. Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation drives convection-limited fluid transport. To demonstrate homology in heart dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held-up2 (hdp2), has impaired systolic and diastolic heart wall velocities. Impaired heart wall velocities occur in the context of a non-dilated phenotype with a mildly depressed fractional shortening. We additionally derive receiver operating characteristic curves showing that heart wall velocity is a potentially powerful discriminator of systolic heart dysfunction. Our results demonstrate physiological homology and support the use of D. melanogaster as an animal model of complex cardiovascular disease.
Highlights
Over the past decade there has been increasing interest in using the open cardiovascular system of Drosophila melanogaster as an animal model of human cardiovascular disease (Bier and Bodmer, 2004)
In conjunction with real-time structural and Doppler optical coherence tomography (OCT) (Huang et al, 1991; Vakoc et al, 2005; Choma et al, 2006; Wolf et al, 2006) imaging of the pre-pupal heart and aorta, we demonstrated that the open cardiovascular system of D. melanogaster has fast, cardiac-cycle-dependent, transport of hemolymph
The results presented here advance the study of the open cardiovascular system of D. melanogaster and support its use as an animal model of complex human cardiovascular disease
Summary
Over the past decade there has been increasing interest in using the open cardiovascular system of Drosophila melanogaster as an animal model of human cardiovascular disease (Bier and Bodmer, 2004). The D. melanogaster cardiovascular system (Fig. 1A) is open because it lacks discrete, closed return vasculature (Vogel, 1993). Previous research has demonstrated genetic, molecular, cellular and tissue function homology between the D. melanogaster and vertebrate cardiovascular systems. The degree of global physiological homology remains an open question. It is unclear whether commonly measured physiological parameters such as cardiac output and aortic velocity, when normalized to measures of body size, are similar between D. melanogaster and important vertebrate species, including humans. Normalization can provide a basis for comparison across different size scales in addition to Received 3 January 2010; Accepted 28 October 2010
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