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Dis Model Mech
2011 May 01;43:411-20. doi: 10.1242/dmm.005231.
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Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems.
Choma MA
,
Suter MJ
,
Vakoc BJ
,
Bouma BE
,
Tearney GJ
.
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The 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.
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21183476
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Fig. 1. Anatomic and functional imaging of the D. melanogaster cardiovascular system. (A) Schematic of an open circulatory system. Flow direction is indicated by dashed arrows. Cardiac cycle (B–H) in pre-pupal D. melanogaster images using sagittal plane OCT imaging (B–D; supplementary material Movie 1) and dye angiography (E–H; supplementary material Movie 2). (I,J) Time-varying pixel intensity at the color-coded landmarks in E. (K) Fourier transform of a segment of J, the time-varying heart pixel intensity. The peaks between 100 and 200 beats per minute (b.p.m.) are consistent with the pre-pupal heart rate. Ao, aorta; h, heart; inj, dye injection site; L, left; lpf, low pass filter; o, ostia; R, right; tr, trachea; v, valve.
Fig. 2. Doppler velocimetry of heart wall motion and intracardiac hemocyte flow. The left panel is an M-mode Doppler/structural image during systole and diastole. The dashed line covers an individual hemocyte that undergoes marked acceleration at the initiation of systole. An accelerating hemocyte could be tracked for ∼10 milliseconds before it exited the field of view of the M-mode line. The right panel is a velocity plot of eight individual hemocytes during distinct cardiac cycles (n=5 organisms). Hemocyte velocity from the dashed line in the left panel is shown in the red line. Hemocyte acceleration was ∼0.2–0.3 m/second2.
Fig. 3. M-mode OCT-based tissue Doppler imaging of wild-type and mutant heart wall velocity. The left panels are representative M-mode images of OreR and hdp2 hearts during systole and diastole. The right panel is a plot of the wall velocity as a function of time, taken along a linear region of interest on the ventral wall. The occasional zero-valued datapoints are Doppler pixels on the linear region of interest that are rejected based on the intensity of the corresponding structural pixel.
Fig. 4. Receiver-operator characteristic (ROC) curves for two measures of systolic heart function: fractional shortening (blue squares) and ventral wall systolic wall peak velocity (green circles). The dashed black line is the 45° line. AUC, area under the curve.
Fig. 5. Focused imaging of aortic flow and wall dynamics. Structural OCT (A–D; supplementary material Movie 5), dye angiography (E; supplementary material Movie 7) and digital subtraction angiography (DSA) (F–J; supplementary material Movie 7). Arrows indicate the aorta. Projection images, taken over 500 milliseconds, clearly outline the course of the aorta and show dye that is delivered to the head over the course of the cardiac cycle. Still frames from the DSA movie clearly show bolus-like transport of dye through the aorta. h, heart.
Fig. 6. Injection near the head demonstrates preferential return flow that is dependent upon the cardiac cycle. After injection, the heart enters a ∼16 second period of asystole. During asystole, there is little transport of dye away from the injection site. This is evident from time-varying plots of local pixel intensity. The small oscillations around baseline at the blue-dot region of interest are probably secondary to head motion (see supplementary material Movie 8). Resumption of the cardiac cycle initiates anterior-to-posterior return flow to the heart. The flow is preferentially along the trachea and dorsal to the aorta.
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