The cardiac response of the goldfish Carassius auratus to environmental hypoxia: from hemodynamics to mitochondria.

Abstract

Under low O₂, the heart of Carassius auratus (goldfish) shows an enhanced hemodynamics. This is observed in ex vivo cardiac preparations from animals acclimated to both normoxia and short-term (4 days) moderate hypoxia and perfused for 90 min with a hypoxic medium. Under short-term hypoxia, this is associated with a higher ventricular muscularity and an expanded mitochondrial compartment. To date, little is known about the putative influence of hypoxia on the mitochondrial contribution to cardiac energy metabolism. Similarly, it remains unexplored whether the exposure to environmental low O₂ affects the cardiac response to preload increases (i.e., the Frank-Starling mechanism). We here observed, on ex vivo isolated and perfused goldfish heart, that 20 days of exposure to moderate water hypoxia are accompanied by a potentiated cardiac performance, analyzed as stroke volume, cardiac output, and stroke work. The sensitivity to preload increases significantly improved after 20 days of hypoxia, while it is similar to normoxia after 4 days of exposure. This suggested a time-dependent response. Mitochondrial O₂ consumption initially decreased during short-term hypoxia but returned to normoxia-like levels after 20 days of exposure. Biomolecular analyses of ventricular extracts revealed a time-dependent regulation of key proteins involved in the mitochondrial biogenesis, including PGC1α, NRF1/2, and TFAM, as well as cytochrome c. Additionally, mitochondrial DNA content was notably increased after 20 days of hypoxia. Our data revealed that, when challenged by chronic environmental hypoxia, the goldfish heart improves its pumping behavior under both basal and loading-stimulated conditions. This is accompanied by a mitochondrial remodeling which likely supports adequate energy supply for the working myocardium.