Men and women respond differently to stimuli, and their hearts respond differently, too. Scientists are continuing to develop an understanding as to why these disparities in physical reactions exist. Before studying the differences in human hearts, a group of scientists at the University of California, Davis started smaller, with male and female mice, to explore whether the way mouse hearts stabilize after stress can tell a tale about how human hearts may respond to stress. The researchers searched for answers within the small frames of mice by measuring the fluorescence associated with a specific chemical reaction related to mouse heart rates. The team used mice that had been genetically modified to generate strong fluorescence in the presence of cyclic adenosine monophosphate (cAMP), which is a cellular messenger that appears during numerous biological processes. During the research, the cAMP production was monitored in conjunction with the functioning of cardiomyocytes, or the cells responsible for contraction of the heart, following an infusion of noradrenaline. Noradrenaline is a hormone that is produced naturally in the common fight-or-flight scenario that all creatures experience. FRET images of the kinetics of cyclic adenosine monophosphate (cAMP) activity in male (top) and female (bottom) hearts at 30-, 60-, 90-, and 130-s intervals after application of the hormone noradrenaline. Adapted with permission from Caldwell et al./Sci Adv/CC By 4.0. The results showed that the heart rates in the female mice recovered more quickly than in the males through a process called repolarization, in which segments of the heart return to a normal rhythm after pumping at an accelerated rate. In the medical community, problems with repolarization have long been connected to various kinds of arrhythmias in humans. To capture this information in the rodent subjects, the researchers used a fluorescence resonance energy transfer (FRET)-based imaging system and voltage-sensitive dye excited with LED light sources. The fluorescence was collected with a THT macroscope produced by SciMedia and then recorded with a CMOS camera. “We had a FRET sensor with a good dynamic range, and this method is used a lot in studying various cell types, including to isolate cardiomyocytes,” said Crystal Ripplinger, senior author of the study and professor in the university’s Department of Pharmacology. “These types of studies have been hard to do in the past because there’s an awful lot of autofluorescence in heart tissue, so we combined FRET with optical mapping to get our results.” In the initial study of repolarization of the heart, the researchers were not looking specifically for gender-related discrepancies in recovery times, although Ripplinger said they hypothesized that they might exist. Now that the researchers are aware of the difference in recovery rates, they know in which direction they will scurry next in their studies. “We were working with healthy hearts in this case, but the next step will be to work with diseased hearts,” Ripplinger said. Her lab group received a grant from the National Institutes of Health to continue the research. She said it was difficult to project corresponding results in human subjects, however, based on the data obtained from mice, due to the much faster heart rates in mice. Nevertheless, a clinical significance will not be hard to visualize. According to Ripplinger, male subjects have traditionally been the focus of both human and mouse heart studies. The team’s work shows that valuable information can be obtained from imaging the conditions in both sexes. The researchers said they plan to nibble away at this goal in the months and years to come. The results showed that the heart rates in the female mice recovered more quickly than in the males through a process called repolarization, in which segments of the heart return to a normal rhythm after pumping at an accelerated rate.