Integrated response of the zebrafish (Danio rerio) cardiovascular system to hypoxia acclimation

Chronic hypoxia exposure of fish can cause remodelling of the gills as well as increases to hematocrit and hemoglobin binding affinity. There is less known however of how chronic hypoxia affects the structure and function of the heart. In the current study zebrafish were exposed to moderate hypoxia for 7 weeks and then ultrasound was used to characterize cardiac function. We found that cardiac output of the hypoxia acclimated fish was greater than that of the control fish during an acute hypoxia exposure. This difference was due, at least in part, to the higher cardiac stroke volume. Histological measurements demonstrated an increase in the cross-sectional area of the ventricle of hypoxia exposed fish and this was supported by higher end diastolic area measurements made using ultrasound. These changes to the heart occurred in conjunction with an increase in hematocrit and the respiratory surface area of the gills, as well as an improved capacity of the fish to respond to a more severe acute hypoxia challenge. We also found an increase in the expression of the gene transcripts for hif-1αa and vegfaa at 24-hours, 3-days, and 8-days of hypoxia exposure suggesting a rapid and consistent response. Our results suggest that, unlike normoxia acclimated fish which demonstrate a decrease in cardiac output with acute hypoxia exposure, zebrafish acclimated to hypoxia maintain cardiac output when acutely exposed to hypoxia.