For most creatures, life without a heart is completely unthinkable. Once an animal develops beyond a certain size, it's impossible for oxygen to reach every cell in the body simply by diffusion. But some water-born larvae are tiny enough to survive perfectly without a cardiovascular system for almost two weeks before their gills begin collecting oxygen for distribution through the body. Which makes these tiny larvae the perfect animals to study if you want to untangle the physiology behind cardiovascular development. Thorsten Schwerte is fascinated by cardiac development and is systematically teasing apart the processes of development, but he adds that the system is so complex that he can only focus on one effect at a time. In the current issue of J. Exp. Biol., he reports how the tiny larvae's developing cardiovascular system responds to hypoxia during the early stages of life().
However, before he could begin following the youngsters' progress, Schwerte decided to design a completely non-invasive technique for visualising blood flow; he turned to the human brain for inspiration. Schwerte explains that we simply can't see some stationary objects, but they instantly become visible when they move. He decided to use microscopic digital imaging to track blood cells moving through the tiny fish's bodies, and to measure blood cell concentrations and locations in the larvae's tissue. First, he anaesthetised the fish, and immobilised individuals in agarose where they rested peacefully as he collected video images of the larvae's cardiovascular system. By collecting enough images, he knew that he could build up a complete view of the fish's vasculature, as well as tracing the path of individual blood cells,to measure their velocity and the total number of cells moving through the tiny blood vessels. With all of these measurements Schwerte, could accurately measure the tiny creatures haematocrit level directly! And he is delighted that after their incarceration in agarose the fish recover quickly, before retiring and passing out the rest of their days in local aquaria.
After months of writing software to interpret the thousands of digital images that he collected, Schwerte could reconstruct the larvae's cardiovascular system, and he began looking for differences between the hyopxic fish's cardiovascular system and fish reared under normoxia. He was amazed to see that the tiny larvae respond to the hypoxic conditions when they were only 5 days old, almost 5 days earlier then oxygen begins to be limited by diffusion. Schwerte thinks that this head start probably gives the youngsters an advantage; he explains that this could be a case of `opening the parachute before you hit the ground'. And when he looked at the distribution of blood cells through the larvae's bodies, not only had the larvae increased their haematocrit levels but they had also shunted their blood supply from the gut to the muscles. Schwerte thinks that this might be a form of the `fight or flight' response, diverting oxygen-carrying cells to the tissue that might help the tiny larvae escape and catch their breath.
Schwerte admits that `it's astonishing what happens, these processes happen at very early stages in development', and he believes that `the zebra fish could form a vital bridge between molecular biology and physiology'. After all, it's not enough to know that a gene plays a role in a disease, it's important to know what the physiological consequences are, and with thousands of zebra fish mutants to study, Schwerte is optimistic that he could soon begin to understand the physiology behind some human cardiac disorders.
