Sex-specific effect of blood O2 carrying capacity on orthostatic tolerance in older individuals

Blood oxygen (O2) carrying capacity is reduced with ageing and has been previously linked with the capacity to withstand the upright posture, i.e., orthostatic tolerance (OT). This study experimentally tested the hypothesis that a definite reduction in blood O2 carrying capacity via hemoglobin (Hb) manipulation differently affects the OT of older women and men as assessed by lower body negative pressure (LBNP). Secondary hemodynamic parameters were determined with transthoracic echocardiography throughout incremental LBNP levels for 1 hour or until presyncope in healthy older women and men (total n=26) matched by age (64±7 vs. 65±8 yr, P<0.618) and physical activity levels. Measurements were repeated within a week period after a 10 % reduction of blood O2 carrying capacity via carbon monoxide rebreathing and analyzed via two-way ANCOVA. In the assessment session, OT time was similar between women and men (53.5±6.1 vs. 56.4±6.0 min, P=0.238). Following a 10 % reduction of blood O2 carrying capacity, OT time was reduced in women compared with men (51.3±7.0 vs. 58.2±2.8 min, P=0.003). The effect of reduced O2 carrying capacity on OT time differed between sexes (mean difference (MD)=-5.30 min, P=0.010). Prior to presyncope. reduced O2 carrying capacity resulted in lower left ventricular end-diastolic volume (MD=-8.11 ml∙m -2, P=0.043) and stroke volume (MD=-8.04 ml∙m -2, 95 % CI=-14.36, -1.71, P=0.018) in women relative to men, even after adjusting for baseline variables. In conclusion, present results suggest that reduced blood O2 carrying capacity specifically impairs OT and its circulatory determinants in older women.

Low-Dose Fentanyl Does Not Alter Muscle Sympathetic Nerve Activity, Blood Pressure, or Tolerance During Progressive Central Hypovolemia

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a pre-syncopal limited progressive lower-body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg•min), which was compared between trials using a paired, two-tailed t-test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model (time [LBNP stage] x trial). LBNP tolerance was not different between trials (Fentanyl: 647 ± 386 vs. Placebo: 676 ± 295 mmHg•min, P=0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: p<0.01, trial: p=0.29, interaction: p=0.94) and reductions in mean BP (time: p<0.01, trial: p=0.50, interaction: p=0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

Abstract P192: Orthostatic Tolerance Before And After 60 Days Of Strict Head Down Tilt Bedrest With And Without Daily Artificial Gravity Training

Background: Orthostatic intolerance occurs after space flight, immobilization and in patients with autonomic diseases, so there is a need for more effective countermeasures. We hypothesized that daily artificial gravity elicited through short-arm centrifugation attenuates plasma volume loss and orthostatic intolerance following 60 days of HDTBR, which models cardiovascular responses to weightlessness. Methods: We studied 24 healthy persons (8 women, 33.4±9.3 yr, 24.3±2.1 kg/m2) exposed to 60d HDTBR. Subjects were assigned to 30 min/d continuous short arm centrifugation (cAG), 6x5 min short arm centrifugation (iAG), or a control group (ctr, no countermeasures). Head-up tilt testing (15 min of 80°) followed by incremental lower body negative pressure (-10 mmHg every 3 min) until presyncope was performed before and at the end of HDTBR. Plasma volume was measured (CO rebreathing) 12-2 days before and after 56d of HDTBR. Stroke volume was measured by cMRI. Norepinephrine, epinephrine, aldosterone, and renine plasma levels were measured before and after HDTBR. Results: Time to presyncope decreased in all groups following bedrest (ctr: 22:56 min pre and 9:35 min post, cAG 15:34 min pre and 10:11 min post; iAG 14:56 min pre and 10:00 min post, p<0.001). The significant interaction (p=0.025) between bedrest and intervention was explained by greater baseline orthostatic tolerance time in the ctr. AG Data was pooled analysis. The reduction in stroke volume (ctr, pre: 93±19 ml, HDTBR: 69±13 ml, AG, pre: 88±20 ml, HDTBR: 67±17 ml) and plasma volume was similar (ctr, pre: 4155±1085 ml, HDTBR: 3855±1087 ml, AG, pre: 4114±1250 ml, HDTBR: 3674± 1313 ml). Catechols and aldosterone did not change significantly during bedrest. The increase in renine was similar between groups (ctr pre: 18±12 mE/L, HDTBR: 21±8 mE/L, AG pre: 21±10 mE/L, HDTBR: 31±12 mE/L). Conclusions: 30 min daily AG didn’t prevent a reduction in orthostatic tolerance following 60d HDTBR. Whether numerically smaller reductions in orthostatic tolerance in the AG groups indicate efficacy or result from baseline differences can’t be ascertained. A stronger AG stimulus or combination with other countermeasures might be required to maintain orthostatic tolerance and to attenuate the volume reduction.

Developing a “dry lab” activity using lower body negative pressure to teach physiology

In this paper we assessed how lower body negative pressure (LBNP) can be used to teach students the physiological effects of central hypovolemia in the absence of the LBNP and/or a medical monitor using a “dry lab” activity using LBNP data that have been previously collected. This activity was performed using published LBNP papers, with which students could explore LBNP as an important tool to study physiological responses to central hypovolemia as well as consider issues in performing an LBNP experiment and interpreting experimental results. The activity was performed at the All India Institute of Medical Sciences, New Delhi, with 31 graduate students and 4 teachers of physiology. Both students and teachers were provided with a set of questionnaires that inquired about aspects related to the structure of the activity and how this activity integrated research and knowledge, as well as aspects related to motivation of the students and teachers to perform the activity. Our results from student and teacher surveys suggest that a “dry lab” activity using LBNP to teach physiology can be an important tool to expose students to the basics of systems physiology as well as to provide useful insights into how research is performed. Providing insight into research includes formulating a research question and then designing (including taking into account confounding variables), implementing, conducting, and interpreting research studies. Finally, developing such an activity using LBNP can also serve as a basis for developing research capacities and interests of students even early in their medical studies.