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Effective neuromotor function may be considered the combination of activating motor units of a type, matching the desired force and fatigue requirements of a behaviour; and the timing of these activations in concert with motor units of other motor pools and/or with contextual/sensory cues. Although the former is well-established as being impaired with age (i.e., sarcopenia), the latter timing issues remain poorly defined in terms of aging. Indeed, sarcopenia may be considered the apotheosis of a degenerative process that first affects the timing and effective activation of motor units prior to overt weakness. We hypothesized that mild motor impairment (i.e., timing deficiencies and motor neuron synaptic pathology) would precede overt striated muscle weakness and motor neuron death. To test this hypothesis, we evaluated the neuromotor system for swallow, where striated muscle activities do not create torque across a joint (a confounder in aging studies) but pressure in the oropharynx and coordination with ventilation. We used female and male Fischer 344 rats (F344) at 6- (young), 18- (late middle-age) and 24-months-old (old) rats. Behavioral evaluations consisted of pharyngeal and thoracic pressures during naturalistic (0.5 ml oral water bolus) swallow. Synapse evaluations consisted of golgi-cox evaluation of nucleus ambiguus and hypoglossal motor neurons, and serial blockface electron microscopy evaluation of hypoglossal motor neurons. We assessed longitudinal (intrinsic) and genioglossus (extrinsic) muscle function and histopathology using platinum plate electrodes and immunohistochemistry for myosin heavy chain (MyHC) expression, respectively. Overall, we show that swallow timing abnormalities occur at late middle-age, contemporaneous with dendritic synaptic and mitochondrial deficits. Notably, motor neuron survival and muscle function and cross-sectional areas were unchanged in late middle- age, with sarcopenia and nucleus ambiguus and hypoglossal motor neuron death only apparent from old age. These results are consistent with the concept of “mild motor impairment” being a harbinger of striated muscle sarcopenia and frailty. There is every reason to suggest that these early motor timing deficits occur in spinal motor neurons. These results illustrate the importance motor neuron health has on maintenance of motor function into old age. Funding: This study was supported by R56 HL166204 & R01 AG086136 (MJF) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Sleep regularity is emerging as an independent determinant of health. Multiple studies suggest a link between increased variability in sleep duration and timing and adverse cardiovascular, metabolic, and cognitive outcomes. There is, however, a lack of data on the implications of sleep regularity for aerobic capacity and physical endurance, particularly in patients with established cardiovascular disease. This study seeks to investigate the influence of irregularity in sleep duration on functional capacity in patients with coronary artery disease (CAD) undergoing cardiac rehabilitation (CR). Methods: We recruited a sample of patients with CAD who were referred to CR at Mayo Clinic Rochester. Participants completed a 6-minute walk test (6MWT) upon enrollment into CR. 6MWT variables included distance walked (meters), predicted distance walked (percentage) and estimated metabolic equivalents (METs). 24-hour objective sleep quality and quantity were assessed over a 7-day period by wrist actigraphy. Average standard deviation (SD) of sleep duration was used to define sleep regularity, with SD >60 minutes indicating irregular sleep. Chi-square test, independent samples t-test, and linear regression were used for statistical analysis. Results: Twenty-eight participants with valid actigraphy and 6MWT were included in this analysis (eight females; mean age 67.4 ± 11.6 years; body mass index 31.1 ± 5.8 kg/m 2 ). The average total sleep time was 7.1 ± 1.2 hours, and 10 participants (35.7%) exhibited sleep duration SD >60 minutes. Demographic, clinical and sleep characteristics were comparable between the regular and irregular sleep groups. Compared to patients with regular sleep, those with irregular sleep had poorer 6MWT, with shorter distance walked (406.2 ± 81.2 meters vs 338.8 ± 80.7 meters; p = 0.045), lower % of predicted distance walked (87.1 ± 18.7% vs 69.2 ± 11.4%; p = 0.011), and lower METS (2.99 ± 0.36 vs 2.63 ± 0.38; p = 0.022). Irregular sleep remained significantly associated with performance at the 6MWT after taking into account age and sex, with patients walking 14.4 meters fewer with every 10-minute increase in sleep variability (95% CI -28.1, -0.7; p 0.041). Conclusions: Increased day-to-day fluctuation in sleep duration is associated with reduced exercise capacity in patients with CAD undergoing CR. These findings add to the mounting body of evidence linking irregular sleep patterns to heightened cardiovascular risk, and support the integration of sleep monitoring in the CR practice to enhance risk stratification and outcome prediction. Funding Source: Sleep Number Corp. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Spasticity after upper motor neuron injury (stroke, spinal cord injury, etc.) alters muscle activity and induces long-term structural remodeling of skeletal muscle [1]. Elbow flexors, including the biceps brachii, are frequently affected, leading to abnormal tone, involuntary co-contraction, and impaired elbow function. Hyper-selective neurectomy (HSN) is a well-established surgical technique that has gained renewed clinical adoption with advances in anatomic understanding and intraoperative nerve mapping [2], yet its effects on muscle properties are poorly defined. Objective: The purpose of this study was to define pre- vs. post-HSN differences in muscle gene expression, sarcomere length, and clinical outcomes of the spastic human biceps. Methods: Individuals with elbow flexor spasticity undergoing a planned two-stage HSN were prospectively enrolled (n=10). Stage 1 released the elbow flexors and provided a pre-biopsy; Stage 2, performed ~3 months later to treat the forearm flexors, provided a second exposure to the biceps and a second biopsy. In both stages, biceps biopsies were obtained with customized clamps [3] at predefined elbow angles (50°, 90°, 135°), fixed, and analyzed for sarcomere length [4]. Total RNA was extracted from pre- and post-HSN biceps samples to characterize transcriptional changes. Clinical spasticity was assessed before Stage 1 and again before Stage 2 using the Modified Ashworth Scale (MAS). Data were compared using repeated-measures models, and single-cell transcriptional changes were analyzed using established analytical pipelines. Results: Sarcomere length (SL) increased significantly after HSN at all joint angles. At 50°, SL increased from 2.45 ± 0.18 µm pre-HSN to 3.05 ± 0.28 µm post-HSN; at 90°, from 2.70 ± 0.29 µm to 2.91 ± 0.16 µm; and at 135°, from 2.72 ± 0.36 µm to 3.24 ± 0.32 µm (all p < 0.05). Clinical spasticity assessment improved significantly as well (p < 0.05), with MAS scores decreasing from 1.89± 0.93 to 0.35 ± 0.53. RNA sequencing revealed changes in key pathways and overall gene expression patterns such as enhanced inflammatory response through increased cytokine production and fibroblast proliferation, leading to elevated collagen synthesis and subsequent fibrosis. We also observed upregulated immune modulation and chemotaxis, while pathways involved in mitochondrial respiration, muscle development, and cellular homeostasis were downregulated. At the transcript level, HSN led to decreased inflammation and adipogenesis, while promoting increased extracellular matrix assembly, and vascular formation. Conclusion: HSN produced coordinated improvements across structural, clinical, and transcriptional levels in the spastic human biceps muscle. Sarcomere lengths increased toward longer resting lengths at all joint angles, clinical spasticity decreased significantly, and RNA sequencing revealed distinct post-operative transcriptional remodeling. The longer sarcomere length and decreased spasticity should contribute to improved patient function after HSN. References: 1. Lieber RL et al. Muscle Nerve. 2002;26:98–105. 2. Leclercq C et al. Hand Clin. 2018;34:537–545. 3. Lieber RL et al. J Neurophysiol. 1994;71:874–881. 4. Ward SR et al. J Biomech. 2009;42:193–196. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Our group has recently reported how acute binge alcohol consumption increases heart rate (HR) and aortic pulsatile load (HR x aortic pulse pressure) in the evening following simulated drinking and the subsequent morning after. However, the influence of acute binge alcohol on the subendocardial viability ratio (SEVR), an estimate of myocardial oxygen supply and demand, has not been reported. We hypothesized that acute binge alcohol consumption would decrease the SEVR within 30 minutes after consumption and the morning after. Participants (n=22; 50% females; age 25±1 years; BMI 27±1 kg/m 2 ) arrived for baseline blood pressure and arterial tonometry measures at 4 pm just prior to a standardized meal. Participants were enrolled into a binge alcohol or fluid control protocol in a randomized order, with one month between visits and received the opposite condition upon laboratory return. Alcohol or fluid control doses were administered in two equal allocates at 8 and 9 pm, and participants were provided 15 min to consume during each allocate period. The blood pressure and arterial tonometry measures were repeated 30 minutes after completion of each fluid consumption, and within 15 minutes of waking the morning after fluid control or binge alcohol consumption within the polysomnographic sleep laboratory. The binge alcohol protocol consisted of a 1:3 mixture of 190 proof grain ethanol and fruit juice (i.e., orange or cranberry juice) based on body weight and sex (1g/kg men, 0.85g/kg women), while the fluid control was only fruit juice in equal volume. Reported data are mean ± standard error, and means were considered significantly different when p< 0.05. The SEVR was significantly reduced from baseline (185±8%) after the first (163±7%; p< 0.001) and second (157±8%; p< 0.001) dose of the alcohol, but unchanged after the first (p=0.890) or second dose (p=0.789) of the fluid control. In the second part of our study, SEVR was significantly lower the morning after binge alcohol than the morning after fluid control (169±7 vs. 185±7%; p=0.009). Binge alcohol consumption decreased SEVR both acutely and the morning-after drinking. These findings highlight how binge alcohol may reduce myocardial perfusion and contribute to ischemic heart disease and cardiovascular risk. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Adipose tissue functions as both a storage depot and endocrine organ and is robustly responsive to a nutrient challenge by increasing blood flow. Alterations in adipose tissue blood flow (ATBF) have been described in conditions of metabolic dysfunction. We hypothesized that aging is associated with decreased perfusion to adipose tissue and that normal weight older adults would have decreased basal and glucose challenged ATBF responsiveness and conductance. We recruited 10 (6F/ 4M) generally healthy, non-diabetic, normal weights subjects aged 18-35 years (Younger YO) and 5 (3F/2M) aged 65 to 80 years (Older adults OA). Volunteers had a DEXA scan; the day of the study, volunteers arrived fasted to the clinical research unit and rested for 30 minutes, before starting ATBF measurements using the xenon washout method. ATBF and blood pressures was measured for 30 minutes at rest (baseline) and at 20, 30, and 60 minutes after ingestion of a 75 g glucose drink. We additionally measured fasting and postprandial plasma insulin concentrations (µIU/mL). Compared to the YO, older volunteers had a slightly elevated mean BMI (25.0 ±0.9 vs. 22.4 ±2.1 kg/m 2 , OA vs YO respectively p < 0.05), total body fat (26±7.4 vs. 17±4.6 kg, p < 0.05), upper body fat (8.7±2.8 vs. 5.1±2.1 kg, p < 0.05) and supine resting systolic pressure (136±18.5 107±11.4 mmHg, p < 0.05 ) compared to YO. Although not statistically significant, YO appeared to have a higher median fasting ATBF at baseline (2.8 ± 3.8 vs 1.8±4.3 ml/100g/min, YO vs. OA, respectively) and in response to the glucose challenge at T20 (3.5±2.7 vs 1.7±2.3), T30 (4.2±3.6 vs 1.8±5.2) and T60 (4.2±4.9 vs 1.4±3.9) compared to OA. Because OA appeared to have lower fasting ATBF, we examined whether ATBF responsivity (percent change from baseline) was altered in OA compared to YO. Compared to baseline, YO adults had a +13% at T20, +43% at T30 and +53% at T60. Conversely, OA had a decrease of 31% at T20, and +11% at T30, and +5% at T60. To account for the higher systolic blood pressure in OA we calculated conductance (ATBF/mean arterial pressure (MAP)) at each timepoint. Conductance was not statistically different between YO and OA at baseline, T20, T30 and T60. Interestingly, ATBF was negatively correlated to total upper body fat in both YO (r = 0.74, p< 0.05) and OA (r =0.67, p=.18). OA had higher fasting insulin concentrations than YO and in early response to OGTT at T20 but not at other timepoints. Plasma insulin was not related to either absolute or responsivity of ATBF at any timepoint. In this ongoing study, our preliminary data suggests that during fasting and in response to a 75 gm OGTT challenge, ATBF responsiveness may be altered in older adults. This suggests that reductions in adipose tissue perfusion and responsivity of perfusion in response to a stimulus known to increase adipose tissue blood flow may be impaired in older adults. Even within this normal weight population there was a strong relationship between upper body fat and ATBF. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Introduction: Menopausal hot flashes are defined as rapid, intense sweating and/or an intense feeling of warmth. Subjective recordings of menopausal hot flashes can be difficult to obtain due to inconvenience to the individual and poor recall. This calls for an improved method to quantify hot flashes that are less dependent on human interaction. The goal of this study was to determine if an ambulatory skin conductance hot flash monitor would detect menopausal hot flash occurrence and frequency to the same degree as those reported by study participants. Methods: Thirty-five peri- and postmenopausal females (age: 53±4 years) participated in this study. An ambulatory, noninvasive sternal skin conductance monitor was placed on each participant for a 24-hour recording period. The monitor recorded a hot flash when an increase of 0.2 micromhos was detected in the participant’s sweat level compared to their baseline (objective). Participants manually recorded perceived hot flash occurrence on the monitor (subjective). For analysis, a monitor recording with ≥20 consecutive hours of intact data was included. Hot flash frequency was defined as the number of hot flashes per recording period. A Mann-Whitney test was conducted to compare subjective and objective hot flash frequencies. Statistical analyses for agreement in hot flash occurrence (yes/no; Cohen’s Kappa) and frequency (Bland-Altman) were completed. Data are reported as mean±SD or median (IQR). Results: The average hot flash monitor recording consisted of 23.8±0.7 hours of data. Twenty-eight females reported at least one hot flash during their recording period (5 [3-9] subjective hot flashes) while 7 females did not report any hot flashes. The monitor detected at least one hot flash in 30 females (10 [5-21] objective hot flashes) and no hot flashes in 5 females. For 3 participants, both the subjective and objective reports showed zero hot flashes. There was a significant difference between the frequency of hot flashes reported by all participants (3 [1-8] subjective hot flashes) and those detected by the hot flash monitor (8 [4-19] objective hot flashes; p=0.006). There was no agreement between the subjective (self-report) and objective (monitor) assessments of hot flash occurrence (k= -0.1734). The Bland-Altman showed a mean bias of 7.1±8.6 towards objective hot flash frequency with limits of agreement of -9.8 to 23.9. Conclusion: The ambulatory sternal skin conductance monitor used in the current study showed no agreement in detecting menopausal hot flashes compared to self-reported hot flashes. Overall, the monitor substantially overestimated the frequency of menopausal hot flashes that participants reported. While further investigation might be needed to improve the monitor’s sensitivity for accurate hot flash detection, it is possible that the monitor may be detecting subclinical menopausal hot flashes that are less recognizable to the individual. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Weight loss and thermogenic dietary supplements often claim to promote weight loss by increasing metabolic activity. This study characterized the identity and quantity of common supplement ingredients. Commercially available products (n=98) whose name, label, or packaging referenced promotion of thermogenesis or weight loss were identified at retail outlets or web search. Product ingredients were divided into 6 possible categories of ingredient quantity based on packaging. Extracts included raw plant ingredients, plant extracts, etc. Small molecule isolates included caffeine, melatonin, etc. The remaining 4 ingredient categories were lipids, minerals, vitamins, and amino acids. Product suggested serving size was 13±16 grams (40±71 Cal). Green tea (521±1334 mg), cayenne (57±46 mg) and black pepper (5±2 mg) extracts were the most common, with 22 ingredients of 137 extracts being quantified 3 or more times. Caffeine (181±59 mg), acetyl-L-carnitine (595±368 mg) and L-carnitine (510±345 mg) were the most common small molecule isolates, with 11 of 49 total ingredients quantified in at least 3 products. There were 18 different lipid or fatty acid ingredients with only linoleic (740±718 mg) and lipoic (250±235 mg) acids being quantified in at least 3 products. Chromium (268±282 µg), calcium (156±110 mg), and iodine (145±85 mg) were the most common minerals, with 10 of 14 minerals quantified in at least 3 products. Cobalamin (49±78 µg), pyridoxine (8±9 mg) and folate (391±252 mcg) were the 3 most common vitamins, with 5 of 13 vitamins quantified in at least 3 products. Alanine (2133±924 mg), tryptophan (60±40 mg) and tyrosine (250±229 mg) were the most common amino acids, with 3 of 9 amino acids quantified in at least 3 products. Ingredients were indicated as “present” but not quantified 541 times across the 98 products. Proprietary formulas and vaguely worded ingredients were listed in 44 of the 98 products. The 98 thermogenic and weight loss products contained a tremendous variety of ingredients, although only 53 of the 240 different ingredients were present in 3 or more products. Variable ingredient content and quantity, complicate blanket claims about function, efficacy, or safety. Future evaluations of ingredient contents should determine if specific amounts confer discernable benefits. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Hypoxia challenges the regulation of arterial oxygenation (SaO 2 ), eliciting a compensatory increase in ventilation ([Formula: see text]E) to preserve blood-gas homeostasis. However, the ability to maintain blood-gas homeostasis during hypoxic exercise may differ between sexes due to differences in chemoreflex drive and the mechanical capacity to augment ventilation. The purpose of this study was to evaluate sex differences in ventilatory and blood-gas responses to progressive hypoxia during moderate walking exercise. Specifically, we asked whether females would be more susceptible to hypoxemia. We hypothesized that females would exhibit a smaller ventilatory response and a less steep ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) compared with males, resulting in a greater reduction in SaO 2 during progressive hypoxia. Methods: Twenty-six physically active adults (15M: age 35.3±9.4; [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 36.2±9.0; [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) were studies during two visits. Visit 1: we determined the participants’ maximal oxygen uptake ([Formula: see text]O 2 max) during an incremental treadmill test. Visit 2: participants walked at ~50% of their [Formula: see text]O 2 max while we reduced the fraction of inspired oxygen (FiO 2 ) progressively every 5 minutes (0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). Arterial blood samples were collected from a brachial artery catheter during the final 30 seconds of each stage; cardiometabolic and ventilatory data were averaged over the final minute of each stage. The test ended when peripheral oxygen saturation (SpO 2 ) fell below 70%. Because 0.13 FiO 2 was the lowest stage completed by all participants, Δ responses were calculated from 0.21 to 0.13 FiO 2 . Independent t-tests compared Δ responses between sexes; data are mean±SD, significance was set at p < 0.05. Results: There was no significant difference in ΔSaO 2 between sexes across hypoxia (M: −22.0±3.7%; F: −22.8±5.5%; p = 0.89). Males had higher arterial oxygen content (CaO 2 ) than females across all stages (M: 20.6±1.2 to 16.0±1.4 mL O 2 ·dL -1 ; F: 18.5±1.1 to 13.8±2.0 mL O 2 ·dL -1 ), but the ΔCaO 2 during hypoxia was not significantly different between sexes (M: −4.6±0.7; F: −4.7±1.4 mL O 2 ·dL -1 ; p = 0.86). Similarly, there was no significant difference in the change in arterial CO 2 (ΔPaCO 2 ) between sexes (M: −5.8±1.5 mmHg; F: −6.5±3.6 mmHg, p = 0.51). In contrast, males exhibited a significantly greater increase in ventilation (Δ[Formula: see text]E: +13.9±4.2 L·min -1 ) than females (+8.6±2.7 L·min -1 ; p = 0.003). Consequently, the ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) was steeper in males (−2.46±0.66 L·min -1 ·mmHg -1 ) compared with females (−1.57±0.68 L·min -1 ·mmHg -1 ; p = 0.004). However, when Δ[Formula: see text]E was expressed relative to maximal ventilatory capacity (%[Formula: see text]Emax), there was no sex difference (M: 8.8±2.6% vs F: 8.3±2.8%; p = 0.68). Conclusion: Females were not more susceptible to hypoxemia than males; both sexes showed comparable reductions in SaO 2 during moderate exercise in progressive hypoxia. Reductions in PaCO 2 were also similar, indicating comparable ventilatory drive. Although males exhibited a larger absolute increase in [Formula: see text]E and a steeper ventilatory CO 2 -response, this difference disappeared when Δ[Formula: see text]E was expressed relative to %[Formula: see text]Emax. These findings indicate that apparent sex differences in ventilation during hypoxia largely reflect differences in ventilatory capacity rather than true differences in oxygenation or ventilatory drive. Taken together, these findings challenge the assumption that females are inherently more susceptible to hypoxemia or have a lower ventilatory drive than males during moderate hypoxic exercise. Funding: NIH T32 DK007352, UL1 TR002377 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Skeletal muscle is a heterogenous tissue composed of fibers (i.e., cells) with distinct metabolic and contractile properties. Muscle fibers are classified into 2 separate groups: Type 1 fibers which are primarily oxidative, and Type 2 fibers (further subdivided to Types 2a and 2x) which are predominantly glycolytic. Acute exercise induces transcriptional changes in skeletal muscle. However, these changes have been studied at the whole muscle level. The effects of exercise on differential gene expression in distinct muscle fiber types in response to acute exercise remains unclear. In this study, we evaluated gene expression in Type 1, 2a, and 2x muscle fibers in response to acute aerobic exercise. Muscle biopsies were collected from 5 (31±3 yrs) apparently healthy individuals before and 3hrs following an acute 45 min session of cycling exercise performed at 65% of maximal heart rate. Individual muscle fibers (n=138) were isolated from the muscle biopsy sample manually under a microscope. Half of the fiber was used to characterize it as Type 1, 2a, or 2x based on its myosin heavy chain isoform expression content using single fiber SDS-PAGE. The other half of the fiber underwent RNA sequencing. The effects of exercise on fiber types were analyzed using subject specific pseudo-bulk differential expression before and after exercise (Type 1 n=28, 2a n=28, and 2x n=12). Gene counts were normalized as counts per million (CPM) and log2 transformed with a pseudocount of +1. The top 200 differentially expressed genes (DEG’s) were then used to calculate fold changes between fiber types at baseline and in response to exercise. After exercise, 73.5% of DEG’s were upregulated in Type 1 fibers, 52% were upregulated in Type 2a fibers, and 60.5% were downregulated in 2x fibers, relative to baseline. Type 1 fibers showed the greatest increases in gene expression (notably, TPM1 log2FC = 2.46, ATP2A1 log2FC = 3.23, and UQCRB log2FC=0.39) and displayed transcriptional changes consistent with oxidative phosphorylation, calcium signaling, and cytoskeletal remodeling pathways. Type 2a fibers displayed modest increases (ATP2A1 log2FC = 0.34, TNNC2 log2FC = 0.21 and ENO3 log2FC=0.35) and an overall upregulation of glycogenic/gluconeogenesis pathways. Conversely, Type 2x fibers exhibited broad transcriptional suppression and downregulation of calcium signaling pathways. In conclusion, acute aerobic exercise induces gene expression in muscle that is fiber type-specific. Type 1 fibers upregulate genes related to oxidative phosphorylation and calcium signaling, whereas Type 2a fibers upregulate genes related to glycolysis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Study objective: To characterize physiologic autonomic dysfunction in humans after chronic spinal cord injury (SCI) relative to uninjured controls and to identify autonomic correlates to neuroimmune deficits. Hypothesis: Individuals with greater autonomic dysfunction after SCI will have more pronounced immune dysfunction, which will be further influenced by sympathetically mediated increases in catecholamine levels. Methodology: Both uninjured controls and individuals with SCI completed a battery of autonomic physiology tests aimed at characterizing preservation of supralesional/sublesional sympathetic activation and global sympathetic inhibition. The autonomic testing battery included 3-minute hand and foot cold pressor tests, 3 Valsalva maneuvers with goal expiratory pressure of 30 mmHg, a novel bladder pressor test (5 minutes of sustained bladder pressure at 35 cmH20 with room temperature sterile water infusion), paced breathing at 0.25 Hz for heart rate/blood pressure variability, and successive doses of bolus intravenous phenylephrine (Oxford technique). A subset of individuals in both cohorts had baseline and cold pressor stressed levels of catecholamines/cortisol drawn and immunologic assessments. Peripheral blood mononuclear cells were extracted from this baseline sample and assessed with flow cytometry for cellular exhaustion markers (CD69, PD-1, TIGIT, TIM-3). Antigen recall response, with/without primed exposure of catecholamines was also completed to identify how sympathetic activation variably impacted functional immune performance with exposure to viral peptides. Data: n=35 uninjured controls; n=29 individuals with SCI Summary of Results: When compared to uninjured controls, individuals with SCI demonstrated significant autonomic dysfunction in all three domains, with decreased supralesional sympathetic activation (Valsalva pressure recovery time, p< 0.0001), abnormal sublesional sympathetic activation (increased bradycardia, p< 0.0001), and impaired sympathetic inhibition (larger dose/body-weight adjusted increase in mean arterial pressure, p=0.0006). As expected, autonomic dysfunction in those with SCI existed on a continuum, with some having largely normal autonomic regulation and others exhibiting profound deficits. Principal component analysis confirmed these three domains as the primary drivers of variability. Cellular exhaustion markers were increased in those with SCI, with positive correlation (R2=0.42) between degree of global autonomic dysfunction (Z-score over 2.0) and CD3+ CD8+ T-cell TIM-3 immunologic exhaustion markers. Antigen recall response was impaired in those with SCI and autonomic dysfunction on physiologic testing, with pronounced decrement in response when catecholamines were added (mean 57% of response lost in CD69 T-cells to Epstein-Barr virus antigen exposure, 53% lost to Flu antigen). Conclusions: In humans with SCI, early evidence supports that individuals have greater autonomic dysfunction and that this is correlated to increased immunologic deficits. Funding Sources: NIH K23HD102663, R01NS115126 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.