To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used 13H INE kinetic methodology to measure forearm NE spillover during intrabrachial arterial Ang II infusions in eight normal male subjects. We used the following protocol to optimize conditions for demonstrating these receptors: (a) lower body negative pressure (-15 mmHg) to increase sympathetic nerve activity to skeletal muscle; and (b) intraarterial nitroprusside to maintain a high constant forearm blood flow (-10 ml/ min* 100 ml) to maximize the proportion of neuronally released NE that spills over into the circulation. During lower body negative pressure, the following were infused intraarterially for three consecutive 20-min periods: saline, Ang II (4 ng/min), and Ang 11( 16 ng/min). During the Ang II infusions, forearm venous NE increased significantly from 173 to 189 and 224 pg/ml (P < 0.01), and forearm NE spillover increased from 384 to 439 and 560 ng/min. 100 ml (P < 0.05 for high Ang II). Forearm NE clearance was unchanged. During low and high dose Ang II, the plasma venous Ang II concentrations were 25 and 97 pM, respectively. Since normal subjects increase plasma Ang II from 4 to 20-22 pM with exercise, standing, or diuretic administration, and patients with severe congestive heart failure can have a plasma Ang II of -25 pM at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress. (J. Clin. Invest. 1994. 93:684-691.) Key words: congestive heart failure* angiotensin-converting enzyme inhibitors . 13H1-norepinephrine kinetics . norepinephrine spillover

During dynamic exercise, blood flow to exercising muscle is closely matched to metabolic demands. This is made possible by metabolic vasodilation, vasoconstriction in inactive vascular beds, and a rise in cardiac output. The sympathetic nervous system plays an important role in regulating this exercise response. In this study, we used steady-state infusions of tritiated norepinephrine ([3H]NE) to determine the magnitude and time course of the arterial NE spillover response to sustained upright bicycle exercise at low (n = 11) and moderate-to-high (n = 14) exercise intensity (25 and 65% of maximum work load, respectively) in normal young subjects. In addition, we sought to examine whether exercise was associated with a change in NE clearance. During 30 min of low-level exercise, arterial NE spillover increased from 1.45 +/- 0.13 to 3.14 +/- 0.30 nmol.min-1 x m-2 (P < 0.01) and appeared to plateau at 20-30 min of exercise; NE clearance remained unchanged. During 20 min of moderate-to-high-intensity exercise, we found a substantial and progressive rise of arterial NE spillover from 2.15 +/- 0.27 to 13.52 +/- 1.62 nmol.min-1 x m-2 (P < 0.01). NE clearance decreased from 0.91 +/- 0.05 to 0.80 +/- 0.05 l.min-1 x m-2 (P < 0.05). These data suggest that, during dynamic exercise, sympathetic nervous system activity is related to exercise intensity, and there appears to be an interaction between the effects of exercise intensity and duration on NE spillover. In addition, at moderate-to-high exercise intensity, a small decrease of NE clearance contributes to the rise in plasma NE.

Approximately 476,000 people on warfarin therapy visit a resort at altitude (>2400 m) annually in Colorado. Clinicians practicing at altitude have expressed concern that ascent to altitude adversely affects coagulation in patients taking warfarin in both high altitude residents and visitors. We sought to determine the effect of ascent to and descent from altitude on coagulation in warfarin patients, as assessed by the international normalized ratio (INR). A retrospective medical chart review was conducted on all warfarin patients treated between August 1998 and October 2003 at a cardiology clinic in which travel to and from altitude was documented in association with each INR measurement in high altitude residents. Of the 1139 INR measurements in 49 patients, 143 were associated with changes in altitude (in 32 of 49 patients). The odds of an INR measurement being below the prescribed range were 2.7 times (95% CI: 1.2-5.8) higher among warfarin patients with recent ascent to altitude, 2.1 times (95% CI: 1.4-3.2) higher among warfarin patients with atrial fibrillation, and 5.6 (95% CI: 2.3-13.7) times higher among warfarin patients with both atrial fibrillation and recent ascent to altitude. Increasing altitude is a risk factor for subtherapeutic INR in warfarin patients and this risk is doubled in atrial fibrillation patients.

BackgroundSurgical trauma care requires excellent multidisciplinary team skills and communication to ensure the highest patient survival rate. This study investigated the effects of Hyper-realistic immersive surgical team training to improve individual and team performance. A Hyper-realistic surgical training environment is defined as having a high degree of fidelity in the replication of battlefield conditions in a training environment, so participants willingly suspend disbelief that they become totally immersed and eventually stress inoculated in a way that can be measured physiologically.MethodsSix multispecialty member US Navy Fleet Surgical/US Army Forward Surgical Teams (total n=99 evaluations) underwent a 6-day surgical training simulation using movie industry special effects and role players wearing the Human Worn Surgical Simulator (Cut Suit). The teams were immersed in trauma care scenarios requiring multiple complex interventions and decision making in a realistic, fast-paced, intensive combat trauma environment.ResultsHyper-realistic immersive simulation training enhanced performance between multidisciplinary healthcare team members. Key efficacy quantitative measurements for the same simulation presented on day 1 compared with day 6 showed a reduction in resuscitation time from 24 minutes to 14 minutes and critical error decrease from 5 to 1. Written test scores improved an average of 21% (Medical Doctors 11%, Registered Nurses 25%, and Corpsman/Medics 26%). Longitudinal psychometric survey results showed statistically significant increases in unit readiness (17%), combat readiness (12%), leadership quality (7%), vertical cohesion (7%), unit cohesion (5%), and team communication (3%). An analysis of salivary cortisol and amylase physiologic biomarkers indicated an adaptive response to the realistic environment and a reduction in overall team stress during performance evaluations.ConclusionsHyper-realistic immersive simulation training scenarios can be a basis for improved military and civilian trauma training.Level of evidenceLevel III.