Randall, Nicholas R.

BACKGROUND AND OBJECTIVES: Vestibular schwannomas (VS) are often phenotypically benign lesions that may be technically challenging to resect because of involvement of neurovascular structures. The anterior inferior cerebellar artery (AICA) is commonly identified near VS, with variable position in relation to the tumor; however, little published literature describes anatomic and pathologic variants of AICA observed during VS resection. METHODS: A prospectively maintained cohort of surgically managed VS with available operative reports and clinical/radiographic follow-up was queried and reviewed for noted aberrations. RESULTS: We identified 66 cases with noted AICA abnormalities among 880 reviewer cases, including 20 loops extending into the internal auditory canal (2.3%), 18 arteries embedded in dura (2.0%), 15 AICA branches directly within VS (1.7%), 8 main trunk arteries coursing between cranial nerves 7 and 8 (0.9%), 3 arteries embedded in temporal bone (0.2%), 1 aneurysm (0.1%), and 1 artery bifurcating cranial nerve 6 (0.1%). The median age of AICA-variant patients was 55 years (range 19-74), and 29 were female (45%). Compared with the other AICA variants, tumors embedded with AICA tended to be larger lesions on maximal axial diameter (2.9 vs 1.6 cm; P = .006), they more commonly underwent less than total resection (73% vs 28%; P = .0001), and they had higher rates postoperative House-Brackmann scores >2 (47% vs 20%; P = .005). Two patients had radiographic and symptomatic postoperative cerebral ischemia or hemorrhage—1 from a bone-encased AICA and 1 from a dural embedded variant. CONCLUSION: Anatomic variants of AICA occur in approximately 7% of VS operations. Most aberrations do not affect surgical or clinical outcomes, and the rate of major vascular injury was low. However, certain types variably add operative time and in the case of AICA encasement in the tumor, likely indicate a more aggressive tumor phenotype with lower rates of gross total resection and high incidences of facial nerve weakness.

Introduction Peripheral nervous system feedback arising from mechanically and metabolically sensitive afferents (Group III/IV, respectively) are central components of the exercise pressor reflex. Experimentally, locomotor venous distention can be simulated via subsytolic regional circulatory occlusion (SubRCO) thereby augmenting the exercise pressor reflex. Furthermore, high pedal frequency increases type II muscle fiber recruitment during exercise likely increasing non‐oxidative metabolism. To date, studies investigating the influence of aging on the exercise pressor reflex have presented conflicting data with most utilizing small muscle mass exercise (e.g. handgrip). Therefore, the purpose of this study was to determine the influence of SubRCO, pedal frequency, and the combination thereof on blood pressure (BP) during exercise in older and younger adults. We hypothesized that during exercise 1) independent of pedal frequencies and age, SubRCO will augment BP and 2) older adults will have greater increases in BP at high pedal frequencies with and without SubRCO compared younger adults. Methods 10 younger (22±2 yrs; 4M/6W; 24±4 kg/m 2 ) and 10 older (63±10yrs; 4M/6W; 24±4 kg/m 2 ) adults participated in two study visits each consisting of two cycling exercise sessions at 20 W, with bilateral upper thigh pressure cuffs. Participants engaged in 3 minutes of exercise at 35 (LOW) or 100 (HIGH) rpm with 5 additional minutes of exercise at that rpm with no cuffing (CTL) or SubRCO in randomized order. Systolic and diastolic blood pressure (SBP and DBP, respectively) were measured via manual sphygmomanometry. Mean arterial pressure (MAP) was calculated as (SBP‐DBP)/3+DBP and the changes in MAP from rest are reported. Results During LOW, SubRCO resulted in greater MAP than CTL in younger (CTL: 4±7; SubRCO: 13±7 mmHg) and older adults (CTL: 4±6; SubRCO: 13±4 mmHg) (both p<0.01). During HIGH, SubRCO resulted in greater MAP than CTL in younger (CTL: 7±4; SubRCO: 20±6 mmHg) and older adults (CTL: 20±9; SubRCO: 31±8 mmHg) (both p<0.01). Younger and older adults had greater increases in MAP during HIGH CTL and SubRCO compared to LOW CTL and SubRCO, respectively (all, p<0.01). Within LOW, there were no differences between younger and older adults during CTL or SubRCO (all, p>0.05). Within HIGH, older adults had greater increases in MAP than younger adults during CTL and SubRCO (both p<0.01). Conclusion These data support the hypothesis that older compared to younger adults have a greater BP response at higher pedal frequencies during exercise. Our results suggest that aging contributes to a greater exercise pressor response to exercise, possibly due to greater feedback from group III/IV afferents. Support or Funding Information NIH HL126638AHA 18POST3990251 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Introduction The exercise pressor reflex contributes to cardiovascular regulation during exercise. The primary components of the exercise pressor reflex response are the mechanically and metabolically sensitive skeletal muscle afferents (group III and IV, respectively). Experimentally, subsystolic regional circulatory occlusion (SubRCO) leads to venous distention, stimulating primarily group III afferents, thereby augmenting the exercise pressor reflex. Previous studies have reported sex differences in the metaboreflex induced exercise pressor reflex induced cardiovascular responses. Specifically, pre‐menopausal women, compared to age‐matched men, were found to have attenuated cardiovascular responses with mechanoreflex stimulation. However, it is unclear if sex differences are also present in the cardiovascular responses during exercise with locomotor limb venous distention. Therefore, the purpose of this study was to determine the influence of SubRCO during submaximal exercise in men and women. We hypothesized that women will have attenuated increases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) than men during exercise with SubRCO. Methods Twelve men and thirteen women completed two study visits (Age: M: 30±6vs. W: 27±8yrs, p>0.05; BMI: M: 25.4±3.6 vs. W: 22±3 kg/m 2 , p<0.05). The first visit consisted of a peak exercise ergometry test. The second visit consisted of constant‐load cycle ergometry at 30% peak workload with different SubRCO pressures via bilateral upper thigh pressure cuffs. The cuffs remained uninflated (0 mmHg) (CTL) during the first three min of exercise, then were intermittently inflated to 20, 40, 60, 80, or 100 mmHg for two minutes (randomized order). Each inflation period was followed by a 2minute deflation period where the participant continued to exercise. Cardiacoutput (Q) and MAP were measured via continuous hemodynamic photoplethysmography and systemic vascular resistance (SVR) was calculated. Data were reported as delta changes from CTL. Results Compared to 0 mmHg, MAP increased with SubRCO inflation pressures of 60, 80, and 100mmHg in men and women during submaximal exercise (all, p<0.05); however, no differences were present between groups (60 mmHg: M: 6.2±4.2 vs. W: 8.0±5.2; 80mmHg: M: 11.6±5.5 vs. W: 15.1±4.8; 100 mmHg: M: 18.2±6.6 vs. W: 20.5±7.2 mmHg(all, p>0.05)). Similarly, SVR increased with cuff inflation pressures of60, 80, and 100 mmHg compared to 0 mmHg in men and women (p<0.05), while no differences existed between groups (60 mmHg: M: 0.3±0.4 vs W: 0.4±0.5;80 mmHg: M: 0.9±0.5 vs W: 1.1± 0.9; 100 mmHg M: 1.3±0.8vs W: 1.5±0.8mmHg/L/min (all, p>0.05)). In contrast, Q did not change with cuff inflation pressures of 20, 40, 60, 80, or100 mmHg compared to 0 mmHg in men or women during submaximal exercise(p>0.05). Conclusion In contrast to our hypothesis, the MAP and SVR responses were not different between men and women with SubRCO during submaximal exercise. Our findings suggest that sex differences are not present in the cardiovascular response to low‐intensity constant‐load exercise with stimulation of the exercise pressor reflex via lower limb venous distention.

Introduction It is well established that the exercise pressor reflex contributes to cardiovascular control (e.g. mean arterial pressure (MAP)) during exercise. One arm of the exercise pressor reflex includes the metabolically sensitive group IV afferents (i.e. metaboreflex). The metaboreflex‐induced cardiovascular responses to exercise are incompletely understood, especially in women across the aging spectrum. For example, post‐menopausal women have greater increases in MAP and systemic vascular resistance (SVR) during locomotor muscle exercise compared to pre‐menopausal women. However, it is unclear if an exaggerated metaboreflex arising from the locomotor muscles is contributing to these cardiovascular adjustments with exercise in post‐menopausal women. We hypothesized that 1) post‐menopausal women will have an augmented MAP response with isolated metaboreflex activation compared to pre‐menopausal women and 2) the exaggerated increase in MAP in the post‐menopausal women will be primarily due to greater increases in SVR. Methods Pre‐ (n= 10, 25±3yrs, 24±3 kg/m 2 ) and post‐menopausal women (n=12, 58±4yrs, 24±3 kg/m 2 ) performed 2 sessions of cycling exercise at 20 W for 5 min with bilateral upper thigh pressure tourniquets inflated to 90 mmHg. At end exercise, the recovery was randomized to post‐exercise circulatory occlusion (PECO) to isolate the metaboreflex (via bilateral upper thigh pressure tourniquets rapidly inflated to suprasystolic pressure for 2 min) or normal recovery (NR) without intervention. Systolic and diastolic blood pressure were measured via manual sphygmomanometry and MAP was calculated. Cardiac output was measured via open circuit acetylene wash‐in and systemic vascular resistance (SVR) was calculated. Data is reported as the absolute change from rest to recovery. Results MAP was elevated during PECO compared to NR in both groups (p<0.05), while MAP during PECO was greater in post‐ compared to pre‐menopausal women (20±9 vs. 13±5 mmHg, respectively) (p<0.05). Similarly, SVR was elevated during PECO compared to NR in both groups (p<0.05), while SVR was greater during PECO in post‐ compared to pre‐menopausal women (5±3 vs. 3±1 mmHg/L/min, respectively) (p<0.05). In contrast, cardiac output was not different between NR and PECO in either pre‐ (NR: 0.3±1 vs. PECO: −0.2±1 L/min) and post‐menopausal (NR: −0.1±1 vs. PECO: −0.7±0.9 L/min) (all, p>0.05). Conclusion These data demonstrate that isolated metaboreflex stimulation following whole‐body exercise results in exaggerated increases in MAP and SVR in post‐ compared to pre‐menopausal women. These data suggest that exercise pressor reflex‐mediated control of MAP during exercise is accentuated in post‐menopausal women with menopause status.

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs. premenopause. Normotensive women in premenopause or postmenopause ( n = 14 and 14; ages: 30 ± 9 and 55 ± 7 yr, respectively; P < 0.01) performed: 1) peak exercise testing and 2) fixed-load cycling at 30% peak workload (48 ± 11 and 38 ± 6 W, respectively; P < 0.01), whereby the initial 3 min were control exercise without RCO (CTL), thereafter including 2 min of bilateral-thigh RCO to 20, 40, 60, 80, or 100 mmHg (randomized), with 2 min deflation between RCO. Both MAP (17 ± 4 vs. 4 ± 4%, P = 0.02) and SVR (16 ± 8 vs. −3 ± 8%, P = 0.04) increased at 80 mmHg from CTL in postmenopause vs. premenopause, respectively. However, cardiac index was similar in postmenopause vs. premenopause at 80 mmHg from CTL (1 ± 6 vs. 7 ± 6%, respectively; P = 0.15). There was no continuous effect of aging in MAP ( P = 0.12), SVR ( P = 0.07), or cardiac index ( P = 0.18) models. These data suggest transient locomotor subsystolic RCO sensitizes musculoskeletal afferents, which provoke increased SVR to generate augmented MAP during exercise in postmenopause. These observations provide a novel approach for understanding the age-independent variability in exercise blood pressure control across the normotensive adult pre- to postmenopause spectrum.