Effects of Exercise Prior to and During Isoproterenol‐Mediated Cardiac Disease
Authors: Olson Courtney Nikole , McLaughlin Nathan , Soo Sherilynn , Luckey Stephen 
Published: June 2021

Cardiovascular disease (CVD), the leading cause of mortality in the United States, is characterized by pathological cardiac hypertrophy and cardiac fibrosis. Exercise has been demonstrated to be an important non‐pharmacological intervention that reduces the progression and adverse effects of CVD. Given the beneficial clinical implications of exercise on CVD, it is important to understand the underlying cardioprotective mechanisms of exercise. Thus, this study was aimed to test the hypothesis that exercise prior to and during isoproterenol administration is cardioprotective and reduces the isoproterenol‐mediated maladaptive changes in the heart. To do this, we used nine‐week old male CBF1 hybrid mice that were placed into either a sedentary group (SED) or exercised voluntarily on a cage wheel (EX) for five weeks. After three weeks, a subset of EX and SED mice were administered either a vehicle solution (VEH) or isoproterenol (ISO, 30 mg/kg/day) using an osmotic pump for the final two weeks of the study. Mice in the SED group remained sedentary for the duration of the study and received either VEH (SED + VEH) or ISO (SED + ISO). Mice in the EX group either continued to exercise for the last two weeks of the study receiving either VEH (EX + VEH(e)) or ISO (EX + ISO(e)) or were sedentary (EX + ISO (s), EX + VEH(s)). While VEH administration did not impact exercise performance in the EX + VEH(e) group, mice in the EX + ISO(e) cohort exercised significantly less. At the end of the treatment period, increased heart size was observed in SED + ISO and EX + ISO(s) mice as compared to their control counterparts (SED + VEH and EX + VEH(s), respectively). While significant cardiac hypertrophy was observed in these mice, there was no difference in cardiac size between these two groups. Interestingly, the mice that continued exercising during ISO treatment, EX + ISO(e), had significantly larger hearts than all of the treatment groups. To better understand the observed morphometric differences, we evaluated cell size and levels of fibrosis in the hearts of these mice. Consistent with the morphometric data, myocyte cross‐sectional area was increased in both the SED + ISO and EX + ISO(s) mice compared to their control counterparts. Moreover, EX + ISO(e) had the largest myocyte cross‐sectional area of all of the hearts. Finally, levels of fibrosis were increased in both SED + ISO and EX + ISO(s) as compared to their control counterparts (SED + VEH and EX + VEH(s), respectively). Surprisingly, the level of fibrosis in these two groups was similar. However, fibrosis was significantly reduced in the hearts of EX + ISO(e) mice as compared to both the SED + ISO and EX + ISO(s) hearts. Our results suggest continuing to exercise during ISO treatment is beneficial and additional studies are required to better understand the impact of exercise prior to and during isoproterenol administration.Support or Funding InformationMJ Murdock Charitable TrustThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.