Helmond, Noud van

Background The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. It is unclear whether exposure to acute hypoxia changes cerebral blood flow during central hypovolemia. We hypothesized that cerebral blood velocity during lower body negative pressure would be lower during hypoxic versus normoxic conditions. Methods Ten healthy subjects (35 ± 3 y, BMI 25 ± 1 kg/m 2 ) were exposed to stepwise lower body negative pressure (LBNP, 5 minutes at 0, −15, −30, and −45 mmHg) during both normoxia and hypoxia (F i O 2 = 0.12–0.15 O 2 ). Normoxia and hypoxia protocols were randomized and blinded. Mean arterial blood pressure (MAP, brachial arterial catheter), middle cerebral artery blood velocity (MCAv, transcranial doppler) and end tidal CO 2 (ET CO2 , mass spectrometer) were continuously recorded. We calculated cardiac output (CO) and total peripheral resistance (TPR) from the arterial pressure waveform. Cerebral vascular conductance (CVC) was calculated as MCAv/MAP. The cumulative stress index (CSI) was calculated as the cumulative product of LBNP pressure and time at each LBNP stage. Results During the hypoxia protocol, 7 participants developed presyncopal symptoms and the protocol was terminated early. Three of these 7 did not complete the normoxia protocol due to presyncopal symptoms as well. Subsequently, CSI was lower during hypoxia (278 ± 63 vs. 513 ± 47 mmHg·min −1 , p < 0.01). MAP (p < 0.01), TPR (p < 0.01), MCAv (p = 0.06) and ET CO2 (p = 0.01) were lower during hypoxia than normoxia – . CO was higher (p = 0.03) during hypoxia than normoxia, while CVC (p = 0.35) was similar. Conclusion The attenuated rise in TPR during the hypoxia protocol was associated with a reduced MAP observed during hypoxia. These findings indicate that lower MCAv and LBNP tolerance during hypoxia are due to reductions in cerebral perfusion pressure (MAP). The similar CVC during both conditions renders it unlikely that significant changes in cerebrovascular resistance contribute to the differences between normoxia and hypoxia in LBNP tolerance and MCAv. Support or Funding Information Funding: W81XWH‐13‐2‐0038 Physiological responses to LBNP with hypoxia and normoxia Baseline LBNP−15mmHg LBNP−30mmHg LBNP−45mmHg MAP, mmHg Normoxia 103 ± 3 104 ± 3 101 ± 3 98 ± 41 Hypoxia 100 ± 3 94 ± 4 93 ± 4 83 ± 4 CO, 1/min Normoxia 4.6 ± 0.3 4.5 ± 0.3 4.1 ± 0.3 3.7 ± 0.31 Hypoxia 5.4 ± 0.3 4.8 ± 0.3 4.1 ± 0.3 3.6 ± 0.3 TPR, mmHg·min·mL −1 Normoxia 22.6 ± 1.3 23.7 ± 1.3 25.0 ± 1.3 26.6 ± 1.41 Hypoxia 18.5 ± 1.3 19.8 ± 1.3 22.7 ± 1.4 23.7 ± 1.6 MCAv, cm·s −1 Normoxia 65 ± 4 64 ± 4 61 ± 4 55 ± 5 Hypoxia 58 ± 4 59 ± 4 57 ± 5 54 ± 6 CVC, cm·s −1 ·mmHg −1 Normoxia 0.67 ± 0.05 0.65 ± 0.05 0.63 ± 0.05 0.58 ± 0.05 Hypoxia 0.61 ± 0.05 0.64 ± 0.05 0.63 ± 0.05 0.64 ± 0.06 ET CO2 , mmHg Normoxia 38 ± 1 38 ± 1 38 ± 1 36 ± 1 Hypoxia 37 ± 1 36 ± 1 35 ± 1 34 ± 2 Different vs. normoxia p<0.06, } indicates a main effect.

Abstract Introduction Dorsal root ganglion stimulation (DRG‐S), has demonstrated superiority in the treatment of complex regional pain syndrome and causalgia. Lead migration and fracture impact DRG‐S therapeutic stability. Lead anchoring reduces DRG‐S lead migration without increasing lead fracture. Lead fracture may be related to lead entrapment in the superficial fascial plane. A novel medialized approach for lead placement and anchoring is presented to address these issues. Methods We suggest an alternative technique for implanting percutaneous DRG‐S leads at the T10‐L5 levels. Results A novel medialized ipsilateral technique for lead placement and anchoring for single, bilateral, and adjacent segment placement is presented. The Tuohy needle puncture site is medial to the pedicle and adjacent to the spinous process, two vertebral levels caudad to the target foramen. Trajectory is maintained in the sagittal plane, to access the caudad interlaminar space near the midline. This technique allows for ipsilateral or contralateral lead placement. After epidural access, the introducer sheath is rotated toward the targeted foramen and advanced. The guidewire followed by the lead is passed, and once lead position is confirmed, tension “S” loops are created, followed by anchoring to the deep fascia. Conclusion We describe a new paramedian technique for DRG‐S lead placement. We propose it will decrease DRG‐S complication rates through anchoring to reduce migration and by avoiding the fascial planes thought to be responsible for fracture. Long‐term outcomes applying our proposed techniques are required for determining the true impact, however, early anecdotal results suggest that these new techniques are favorable.

Background Central hypovolemia elicited by hemorrhage triggers sympathetically‐mediated baroreflex responses to maintain organ perfusion through peripheral vasoconstriction; humans with low tolerance (LT) to central hypovolemia have a diminished vasoconstrictor response during progressive reductions in central volume. Using the lower body negative pressure (LBNP) hemorrhage model, we tested the hypothesis that humans with LT to central hypovolemia would display attenuated resting beat‐to‐beat neuro‐hemodynamic transduction of muscle sympathetic nerve activity (MSNA) compared to those with high tolerance (HT). Methods MSNA (microneurography, peroneal nerve) and diastolic arterial pressure (DAP; finger photoplethysmography) were recorded in 33 human subjects (23 men, 10 women, age: 31 ± 9 years, BMI: 26 ± 4 kg/m 2 ) who subsequently underwent LBNP to tolerance (onset of pre‐syncopal symptoms) – Figure 1. Consistent with previous studies, subjects were classified as LT if they experienced pre‐syncopal symptoms prior to completing LBNP of −60 mm Hg, or as HT if they experienced pre‐syncopal symptoms after completing LBNP of −60 mm Hg. We performed linear regression analysis on data of binned MSNA burst areas against DAP; the slope of this regression represents transduction. Results Of the 33 subjects, 8 exhibited LT (time to pre‐syncope for LT: 17 ± 2 min and HT: 27 ± 5 min) Contrary to our hypothesis, resting beat‐to‐beat neuro‐hemodynamic transduction was not different between LT and HT subjects (median 0.09 IQR 0.03 – 0.16 mmHg (%s) − 1 vs. median 0.12 IQR 0.06 – 0.16 mmHg (%s) − 1 , respectively, p = 0.44) and was not related to time to pre‐syncope ( p = 0.70). Conclusion Tolerance to simulated blood loss is not related to resting sympathetic neuro‐hemodynamic transduction. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

We tested the hypothesis that hemodynamic responses would be similar during lower body negative pressure (LBNP) and hemorrhage (HEM). We measured central venous pressure (CVP), mean arterial pressure (MAP), and heart rate (HR) in 6 men during LBNP and HEM. The LBNP protocol consisted of 5‐minute stages at 0, ‐15, ‐30, and ‐45 mmHg of pressure. After a 45 minute break, the HEM protocol began and included 5 minutes at baseline and following three stages of 333 mL of HEM (1 L total). HR during LBNP increased from baseline to ‐45 mmHg (61 ± 3 vs. 86 ± 10 bpm, P < 0.01) while HR was unchanged after 1 L HEM (59 ± 4 vs. 66 ± 5 bpm, P = 0.07). HR was higher during LBNP at ‐30 mmHg vs. HEM at 667 mL (71 ± 7 vs. 63 ± 4 bpm, P = 0.03) and at the final stage (P < 0.01). From baseline, MAP tended to be reduced to a similar degree during ‐45 mmHg LBNP (90.9 ± 3.0 vs. 82.2 ± 4.0 mmHg) and 1 L HEM (89.5 ± 2.1 vs. 80.8 ± 4.0 mmHg) (P = 0.06). From baseline, CVP declined similarly during −45 mmHg LBNP (7.9 ± 1.1 vs. 0.1 ± 1.2 mmHg, P < 0.01) vs. 1 L HEM (5.8 ± 1.1 vs. 1.1 ± 1.4 mmHg, P < 0.01). Using the amalgamated r 2 across each level of LBNP and HEM, HR ( r 2 = 0.98, P < 0.01) and CVP were significantly correlated ( r 2 = 0.98, P < 0.01), but MAP was not ( r 2 = 0.53, P = 0.27). Although LBNP models the changes in MAP and CVP observed in HEM, differences in the HR response to LBNP and HEM require further exploration. Funding: US Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11–1‐0823.

We tested the hypothesis that the catecholamine response would be similar during lower body negative pressure (LBNP) vs. blood loss (BL). Twelve men underwent randomized LBNP and BL protocols on the same day. LBNP consisted of 5‐minute stages at 0, ‐15, ‐30, and ‐45 mmHg of pressure. The BL protocol included 5 minutes at baseline and then after three stages of 333 ml of whole blood draws (1000 ml total) which were stored for reinfusion. Central venous pressure (CVP) was recorded during each protocol. Blood samples were collected at baseline and at the end of the last stage of each protocol. CVP was greater in LBNP vs. BL at baseline (7.3 ± 0.6 vs. 6.1 ± 0.6 mmHg; P < 0.01) and was lower during LBNP vs. BL (‐0.2 ± 0.6 vs. 1.8 ± 0.8 mmHg; P < 0.01). The increase in epinephrine (EPI) during LBNP (53 ± 7 vs.144 ± 30 pg/ml) and BL (49 ± 7 vs. 103 ± 19 pg/ml; P < 0.01) was similar (P = 0.16). An increase in norepinephrine (NE) during LBNP (148 ± 20 vs. 354 ± 44 pg/ml; P < 0.01) was greater (P < 0.01) than the trend to increase during BL (155 ± 22 vs. 211 ± 29 pg/ml; P = 0.09). Individual slopes of catecholamines vs. CVP were calculated to determine if the responses had similar trajectories between the two protocols. The EPI vs. CVP slope was steeper in LBNP vs. BL (‐13.5 ± 4.6 vs. ‐0.6 ± 0.1 pg/ml/mmHg; P < 0.01). The NE vs. CVP slope was steeper in LBNP vs. BL (‐27.8 ± 5.6 vs. ‐8.7 ± 5.9 pg/ml/mmHg; P = 0.01). LBNP to ‐45 mmHg appears to be a greater sympathetic stressor than 1000 ml of BL. Grant Funding Source : Supported by US Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11‐1‐0823

Due to the relationship between stroke volume (SV) and pulse pressure (PP) during lower body negative pressure (LBNP), we hypothesized that PP reflects SV during hemorrhage (HEM). After a 5‐minute baseline, 6 men were exposed to LBNP at ‐15, ‐30, and ‐45 mmHg for 5 minutes at each pressure. After 45 minutes of recovery, three progressive 333‐ml stages of HEM (1 L total) were performed. SV was assessed using a CC Nexfin and PP was calculated using an arterial catheter. SV (111 ± 2.1 vs. 77 ± 6.7 mL; p = 0.04) and PP (58±2.7 vs. 41 ± 4.3 mm Hg; p = 0.03) decreased from baseline to ‐45 mmHg LBNP. SV (118 ± 4.4 to 99 ± 6.8 mL; p = 0.06) and PP decreased (58 ± 2.9 to 48 ± 4.9 mmHg; p = 0.06) from baseline to ‐1 L of HEM. PP correlated with SV during HEM (amalgamated r 2 = 0.98) and LBNP (amalgamated r 2 = 0.99). There was limited inter‐subject variability in PP vs. SV during LBNP ( r 2 range 0.57 to 0.99, 5/6 had an r 2 >; 0.90), but substantial inter‐subject variability during HEM ( r 2 range 0.21 to 0.99, 2/6 had an r 2 >; 0.90). Reductions in PP induced by LBNP or HEM are strongly correlated with SV. However large inter‐individual differences in this correlation during HEM, which may indicate a significantly variable compensatory response in human arterial distensibility, may limit the use of PP as a surrogate for SV during clinical blood loss. Funded by U.S. Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11–1‐0823.

Hypovolemia‐induced sympathoexcitation might initiate an immune response through an increase in circulating epinephrine and splenic demargination. We tested the hypothesis that lower body negative pressure (LBNP) and blood loss (BL) result in comparable increases in white blood cell counts (WBCs). We determined WBCs and epinephrine levels in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5‐minute stages at 0, ‐15, ‐30, and ‐45 mmHg of suction. BL included 5 minutes at baseline and following three stages of 333 mL of blood removal (up to 1000 mL total). Blood draws were performed at baseline and after the last stage of each protocol. LBNP to −45mmHg was a greater central hypovolemic stimulus vs. BL, therefore WBCs and epinephrine concentrations were plotted against central venous pressure (CVP) to obtain stimulus‐response relationships using the linear regression line slopes for both protocols. Paired tests were used to determine if the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes fell on similar trajectories for total WBC (LBNP 183±46 vs. BL 155±109 mcL −1 *mmHg −1 , p=0.15), neutrophils (LBNP 110±29 vs. BL 96±72 mcL −1 *mmHg −1 , p=0.15) and lymphocytes (LBNP 65±21 vs. BL 59±38 mcL −1 *mmHg −1 , p=0.90). Mean regression line slopes for epinephrine were similar as well (LBNP 15±5 vs. BL 16±4 pg *mL −1 *mmHg −1 , p=0.84). Our results indicate that LBNP models the stimulus‐response relationship between CVP and WBCs observed during BL. Central hypovolemia, induced by LBNP or BL, elicits a relative leukocytosis with a predominantly neutrophil‐based response. Support or Funding Information US Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11‐1‐0823

Background Sympathetic nerve activity and its effect on blood pressure are altered by female sex hormones; however, this effect differs between exogenous and endogenous hormones. With oral contraceptive (OC) use, cross‐sectional data has demonstrated higher blood pressure (BP) with no corresponding change in muscle sympathetic nerve activity (MSNA). This results in a higher BP/MSNA ratio with OC use although contributing mechanisms are unclear. The higher BP/MSNA ratio in women on OC suggests OC use may limit the ability of sympathetic baroreflex (sBRS) to suppress MSNA. Alternatively, a “burst” of MSNA could result in a greater change in BP (augmented neurovascular transduction). Objective The goal of this study was to determine if OCs alter blood pressure control through autonomic mechanisms in young women. Hypotheses We hypothesized (1) sympathetic baroreflex sensitivity would be decreased and (2) neurovascular transduction would be augmented in women on OCs compared to naturally cycling women. Methods We conducted a retrospective analysis of data from healthy young women taking OCs (n=30, 25±4yrs) and with natural menstrual cycles (n=23, 27±4yrs). Women were studied during the placebo phase of OC use or early follicular phase of the menstrual cycle. Heart rate (HR, 3‐lead ECG), BP (arterial line or photoplethysmography for both groups), and MSNA (peroneal nerve microneurography) were measured over 5 min of quiet rest and data were analyzed for measures of sBRS and neurovascular transduction (Ensemble, Elucimed Inc., Dunedin, New Zealand). Results Groups did not differ in mean BP (Control: 94±9, OC:92±8mmHg, p=0.60), or HR (Control: 61±8, OC: 62±9 bpm, p=0.57), but women on OCs had lower MSNA than controls (Control: 16±6, OC: 12±5 bursts/min, p=0.006). There were no significant differences in TPR (Control: 0.022±0.005, OC: 0.020±0.005 mmHg min/L, p=0.12), however there was a trend toward increased cardiac output in women on OCs (Control: 4.45±0.86, OC: 4.94±1.02 L/min, p=.068). There were no significant group differences in sBRS (Control: −4.3±2.1, OC: −4.0±2.6 bursts ·100 heartbeats −1 ·mmHg −1 , p=0.79), or neurovascular transduction (Control: 0.093±0.042, OC: 0.091±0.058 ΔmmHg/% burst area, p=0.87). Furthermore, there were no significant correlations between BP and BRS, MSNA, or transduction in either group. Conclusions Our data strengthen previous findings which have shown women taking OCs have higher BP for a given MSNA. The analysis we performed build on these results and demonstrate that the increase in BP for a given MSNA in women taking OCs is not due to attenuated sBRS or augmented neurovascular transduction. This work has advanced our understanding of the alteration of blood pressure with OC use in young women. Support or Funding Information NIH HL083947