WASHINGTON -- The heart is one of the most energy demanding organs of the human body. Its failure to function properly accounts for 600,000 deaths each year. Similarly, the rainbow trout, native to the Pacific Northwest and beloved as a sport- and food fish, requires dynamic and sustained cardiac function to maintain its health and swimming activity.
Previous studies of trout cardiac performance and energy metabolism have been conducted under hypoxic (oxygen shortage) conditions, but gender was not specifically examined. Nor were comparisons made between male and female fish (the largest group of vertebrates) made. There is a growing appreciation of significant sex differences in cardiac characteristics and function in adult humans. A new research study begins to close the gender gap in fishes, and finds that sex differences in cardiac performance and metabolism exist in rainbow trout. These differences occur at a young age and are only realized when the trout heart is contracting and not under resting conditions.
The study is entitled Sex Differences in Cardiac Glucose Metabolism and Function in Immature Rainbow Trout (Oncorhynchus mykiss). It was conducted by Pavan K. Battiprolu, Adam C. Goddard and Kenneth J. Rodnick, all of the Department of Biological Sciences, Idaho State University, Pocatello, Idaho. Dr. Rodnick's laboratory is presenting the team's findings at the 120th American Physiological Society (APS; www.the-APS.org) annual meeting, which is being held as part of the Experimental Biology (EB '07) conference. More than 12,000 scientific researchers will attend the gathering being held April 28-May 2, 2007 at the Washington, DC Convention Center.
The Study
The researchers examined if two regulatory molecules found in the fish heart -- citrate (an acid which inhibits the glycolytic metabolic pathway) and pyruvate dehydrogenase (PDH), the enzyme allowing carbohydrates to be oxidized -- differ between the sexes. The researchers hypothesized that male hearts would have higher citrate levels and females would benefit more from the stimulation of PDH than males.
The study also sought to determine if sodium cyanide (NaCN) -- an inhibitor of oxidative metabolism ¡V decreases activity of the glycolytic pathway and cardiac performance in both sexes, and if males possess a larger outermost (epicardial) layer of the ventricle vs. the inner endocardium layer. The trout heart is a composite organ and layer distinction is important because the epicardium, much like the human heart, receives oxygenated blood via the coronary circulation. Conversely, the endocardium is supplied by only deoxygenated blood returning from the rest of the body. Not surprisingly, the authors expect there to be corresponding layer differences in energy production and function.
Methodology
Uniform ventricle strips or transverse rings were cut from 10-12 month old, hatchery raised, sexually-immature male and female rainbow trout. Each strip was prepared in one of two ways: (1) incubated without stimulation (i.e., ventricle strips were incubated in a respiration cell containing an oxygenated buffer solution with glucose as the energy substrate). Oxygen consumption was measured using a calibrated oxygen electrode and data acquisition system; or (2) electrically-paced (i.e., ventricle strips were electrically-stimulated at physiological rates and temperature in tissue baths containing buffer, with (a) glucose and (b) glucose + DCA (dichloroacetate, an activator of PDH and a therapeutic drug used to treat human heart disease and cancer), or (c) glucose + NaCN under oxygenated and hypoxic conditions.
The researchers measured several indices of contractile performance (resting tension, twitch force, post-rest potentiation and other variables. Frozen samples of ventricle tissue were homogenized and assayed for citrate concentration. Ventricle rings were processed, sectioned and stained. Light microscopy was used to capture images of ventricle layers and analyzed for layer cross-sectional areas. Lactate concentration and net lactate release from cardiac tissue was also examined.
Results
The researchers found:
- ventricle strips from males and females had similar rates of oxygen consumption and lactate release under resting conditions;
- the inhibition of oxidative metabolism with NaCN lowered cardiac performance dramatically, and elevated resting tension and lactate release in both males and females;
- under stimulated conditions with DCA vs. controls, female ventricle strips selectively demonstrated better performance and reduced lactate release;
- force production during reoxygenation -- after a hypoxic insult -- significantly improved in males receiving DCA, but not females;
- male ventricle tissue had 2.5-fold higher citrate concentrations than females; and;
- males had a proportionately larger epicardium to endocardium ratio compared with females with similar size hearts.
Summary and Conclusions
This study expands upon previous findings that sex differences in cardiac performance and metabolism exist in fish in general, and have now been found to occur in rainbow trout in particular. Moreover, the differences are only realized during working conditions and involve stimulation or inhibition of the glycolytic pathway and carbohydrate oxidation. Ultimately, sex differences in cardiac energy metabolism and function may help define habitat suitability, swimming capabilities and health status of wild and hatchery-reared rainbow trout, and human heart disease, sex-specific treatment.
The research was funded by the NIH (grant # P20 RR16454 from the BRIN-INBRE Program of the National Center for Research Resources) and NSF (award # IOB-517669).
The American Physiological Society (APS) has been an integral part of the scientific discovery process since it was established in 1887. Physiology is the study of how molecules, cells, tissues and organs function to create health or disease.
NOTE TO EDITORS: The APS annual meeting is part of the Experimental Biology 2007 (EB '07) gathering and will be held April 28-May 2, 2007 at the Washington, DC Convention Center. To schedule an interview with Dr. Rodnick, please contact Donna Krupa.