Moir, M. Erin

Dynamic cerebral autoregulation (CA) refers to the brain's ability to maintain stable cerebral blood flow despite fluctuations in blood pressure (BP). Impaired CA has been associated with cardiovascular disease severity and cognitive decline. On the other hand, enhanced cardiorespiratory fitness appears to be protective against both cerebrovascular dysregulation and cognitive decline, with an unclear link between the two. However, among individuals with cardiovascular disease, the impact of exercise-based cardiac rehabilitation (CR) on CA remains unclear. Therefore, the aim of this study was to test the hypothesis that a 12-week CR program would improve dynamic CA in adults with CVD. To address this question, data were collected from 14 patients enrolled in the Mayo Clinic CR program following a cardiac-related hospital admission (age: 43-70 yrs; n=3 females), which included moderate-high intensity aerobic exercise 3 times/week for 12-weeks. Continuous measures of middle cerebral artery velocity (MCAv; transcranial doppler) and finger BP (photoplethysmography) were obtained during 3-minutes of rest and a 3-minute sit-to-stand protocol (0.025Hz frequency) pre- and post the CR program. Transfer function analyses were used to provide an index of dynamic CA. BP-MCAv coherence in the low frequency (LF) and very low frequency (vLF) domains at rest were not different pre- and post- CR (LF: 0.48±0.19 vs 0.43±0.16; P=0.54; vLF: 0.51±0.12 vs 0.47±0.16; P=0.14). Similarly, gain and phase values at rest were not different pre- and post- CR (gain LF: 0.66±0.37 vs 0.58±0.33; P=0.16; vLF: 0.87±0.53 vs 0.74±0.43; P=0.21; phase LF: 0.41±0.30 vs 0.43±0.26; P=0.64; vLF: 0.72±0.53 vs 0.66±0.16; P=0.18). In contrast, during the sit-to-stand protocol, coherence was lower following CR (pre vs post LF: 0.81±0.13 vs 0.79±0.16; p<0.01; vLF: 0.80±0.09 vs 0.79±0.14; p<0.01). In addition, gain was reduced post CR (pre vs post LF: 0.59±0.35 vs 0.55±0.31; P=0.02; vLF: 0.76±0.33 vs 0.61±0.37; p<0.01), suggesting CR-induced improvements in CA efficiency. However, phase remained unchanged pre- and post- CR during the sit-to-stand protocol (LF: 1.01±0.71 vs 0.84±0.58; P=0.17; vLF: 1.16±0.69 vs 1.08±0.60; P=0.19). Taken together, these findings demonstrate that a 12-week exercise-based CR program improves dynamic CA efficiency after a cardiac event. These novel results highlight the potential role of exercise training in improving cerebrovascular regulation. Funding: NIH AG073726 and Mayo Clinic This abstract was presented at the American Physiology Summit 2025 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.

Discrete physiological stressors differentially affect sympathetic postganglionic neuronal rate-, population-, and temporal-coding strategies. When performing end-expiratory apnea (APN) during graded baroreflex unloading via lower body negative pressure (LBNP): 1) augmented sympathetic neuronal firing probability, 2) recruited larger and previously silent sympathetic postganglionic neurons at ambient and −10 mmHg, but not −40 mmHg LBNP, and 3) reduced neuronal discharge latency similarly across all conditions, independent of the level of baroreflex unloading.

What strategies are employed by the sympathetic system to communicate with the circulation? Muscle sympathetic nerve activity (MSNA) occurs in bursts of synchronous action potential (AP) discharge, yet whether between-burst asynchronous AP firing exists remains unknown. Using multiunit microneurography and a continuous wavelet transform to isolate APs, we studied AP synchronicity within human MSNA. Asynchronous APs were defined as those which occurred between bursts. Experiment 1 quantified AP synchronicity in eight individuals at baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and end-expiratory apnea (APN). At BSL, 33 ± 12% of total AP activity was asynchronous. Asynchronous discharge was unchanged from BSL (67 ± 37 AP/min) to −10 mmHg LBNP (69 ± 33 AP/min), −40 mmHg LBNP (83 ± 68 AP/min), or APN (62 ± 39 AP/min). Across all conditions, asynchronous AP probability and frequency decreased with increasing AP size. Experiment 2 examined the impact of the ganglia on AP synchronicity by using nicotinic blockade (trimethaphan). The largest asynchronous APs were derecruited from BSL (11 ± 4 asynchronous AP clusters) to the last minute of the trimethaphan infusion with visible bursts (7 ± 2 asynchronous AP clusters). However, the 6 ± 2 smallest asynchronous AP clusters could not be blocked by trimethaphan and persisted to fire 100 ± 0% asynchronously without forming bursts. Nonnicotinic ganglionic mechanisms affect some, but not all, asynchronous activity. The fundamental behavior of human MSNA contains between-burst asynchronous AP discharge, which accounts for a considerable amount of BSL activity. NEW & NOTEWORTHY Historically, sympathetic nerve activity destined for the blood vessels supplying skeletal muscle (MSNA) has been characterized by spontaneous bursts formed by synchronous action potential (AP) discharge. However, this study found a considerable amount (~30% during baseline) of sympathetic AP discharge to fire asynchronously between bursts of human MSNA. Trimethaphan infusion revealed that nonnicotinic ganglionic mechanisms contribute to some, but not all, asynchronous discharge. Asynchronous sympathetic AP discharge represents a fundamental behavior of MSNA.