Background: Frailty is strongly associated with low physical and cardiorespiratory fitness, and unfortunately is observed in 20-50% of the ~50 million adults that experience surgical stress in the U.S. each year. The peripheral microvasculature may serve as a potential target to increase resilience to stress and improve postoperative outcomes. A better understanding of how the microvasculature responds to stress in elderly individuals with low fitness is thus needed. Objective: To define the relationship between cardiorespiratory fitness and microvascular resiliency to stress in elderly individuals. Hypothesis: Elderly individuals with low cardiorespiratory fitness will show acute reductions in acetylcholine (Ach)-mediated dilation of the skin microvasculature following the physiological stressful stimulus of high intensity interval exercise (HIIE). Methods: This was a prospective, observational study that enrolled elderly individuals aged 65-85 years from the community. Each participant was asked to complete two study visits. During visit 1, participants completed the Frailty Index and performed a graded cardiopulmonary exercise test (CPET) on a cycle ergometer with a metabolic cart to measure peak total body oxygen consumption (VO2 Peak). During visit 2, laser Doppler flowmetry with dermal microdialysis was performed on the ventral forearm to measure peak cutaneous microvascular vasodilation to Ach (10 mM). After baseline assessment, the participants performed a HIIE protocol where they repetitively switched between exercising at 70% of the peak workload achieved during the CPET for 60 seconds, followed by a 60 second active recovery at 10 watts. These intervals were repeated 12 times, for a total exercise duration of 24 min. Thirty minutes following exercise, Ach-mediated dilation of the cutaneous microvasculature was reassessed. Maximum dilator capacity of each site was assessed by infusing sodium nitroprusside (28 mM) and heating the skin to 43 °C. Results: Six individuals (1 male, 5 females; mean age 68 ±4 years) completed all study procedures. Based on age- and sex-predicted normative values for VO2 Max, three of the individuals had high physical fitness while three had low fitness (mean VO2 Peak = 27.5±1.1 vs. 13.6±3.4 ml/kg/min, respectively). Prior to HIIE there was no difference in peak dilation to Ach between the individuals with high vs. low fitness (% max dilation = 72±13 vs. 83±13, respectively). During HIIE, the individuals reached a Borg rating of perceived exertion of 15±4 (out of 20) and their peak heart rate was 74±15% of their age-predicted maximum. Ach-mediated dilation of the dermal microvasculature was reduced following HIIE in elderly individuals with low cardiorespiratory fitness (pre vs. post % maximum dilation = 82±13 vs. 49±27, respectively; mean change = -34±40 %) but unchanged in those with high fitness (pre vs. post % maximum dilation = 72±13 vs. 78±10, respectively; mean change = 5±3 %). Using Pearson correlation tests there was a strong correlation between the change in peak Ach-mediated dilation pre vs. post HIIE and both VO2 Peak (r=0.82, p=0.04) and Frailty Index score (r=-0.98, p<0.001). Conclusion: Microvascular resilience to acute stress is decreased in elderly individuals with low cardiorespiratory fitness compared to those with high fitness. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.