Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models
The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lac...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2017-01-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/10/1/63 |
| _version_ | 1818487050876223488 |
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| author | Louis W. Wang Inken G. Huttner Celine F. Santiago Scott H. Kesteven Ze-Yan Yu Michael P. Feneley Diane Fatkin |
| author_facet | Louis W. Wang Inken G. Huttner Celine F. Santiago Scott H. Kesteven Ze-Yan Yu Michael P. Feneley Diane Fatkin |
| author_sort | Louis W. Wang |
| collection | DOAJ |
| description | The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency echocardiography allows reliable in vivo cardiac assessment in adult zebrafish and make recommendations for optimizing data acquisition and analysis. This enabling technology reveals new insights into zebrafish cardiac physiology and provides an imaging platform for zebrafish-based translational research. |
| first_indexed | 2024-12-10T16:32:06Z |
| format | Article |
| id | doaj.art-8a4480fe0253426497e0da733658acff |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-10T16:32:06Z |
| publishDate | 2017-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-8a4480fe0253426497e0da733658acff2022-12-22T01:41:31ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112017-01-01101637610.1242/dmm.026989026989Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease modelsLouis W. Wang0Inken G. Huttner1Celine F. Santiago2Scott H. Kesteven3Ze-Yan Yu4Michael P. Feneley5Diane Fatkin6 Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency echocardiography allows reliable in vivo cardiac assessment in adult zebrafish and make recommendations for optimizing data acquisition and analysis. This enabling technology reveals new insights into zebrafish cardiac physiology and provides an imaging platform for zebrafish-based translational research.http://dmm.biologists.org/content/10/1/63ZebrafishEchocardiographySex differencesCardiac physiologyHeart failureRegeneration |
| spellingShingle | Louis W. Wang Inken G. Huttner Celine F. Santiago Scott H. Kesteven Ze-Yan Yu Michael P. Feneley Diane Fatkin Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models Disease Models & Mechanisms Zebrafish Echocardiography Sex differences Cardiac physiology Heart failure Regeneration |
| title | Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models |
| title_full | Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models |
| title_fullStr | Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models |
| title_full_unstemmed | Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models |
| title_short | Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models |
| title_sort | standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models |
| topic | Zebrafish Echocardiography Sex differences Cardiac physiology Heart failure Regeneration |
| url | http://dmm.biologists.org/content/10/1/63 |
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