P. K. Opstad

Moderate hypothermia blunts the inflammatory response and reduces organ injury after acute haemorrhage

Background: Reduced body temperature is a common companion to trauma/haemorrhage. Several clinical studies have identified hypothermia as an independent risk variable predisposing to increased morbidity and mortality. At the same time it is known that most enzymatic reactions are downregulated at temperatures below 37°C. Theoretically this should restrain the inflammatory response and protect the host from remote organ injury. The study was performed to test this hypothesis.

Glycine – an important neurotransmitter and cytoprotective agent

Background:  Glycine, the simplest of the amino acids, is an essential component of important biological molecules, a key substance in many metabolic reactions, the major inhibitory neurotransmitter in the spinal cord and brain stem, and an anti‐inflammatory, cytoprotective, and immune modulating substance.

THE THYROID FUNCTION IN YOUNG MEN DURING PROLONGED EXERCISE AND THE EFFECT OF ENERGY AND SLEEP DEPRIVATION

Thyroid function has been investigated in 24 young military cadets participating in a 5 d ranger training course with heavy physical excercise, calorie deficiency and deprivation of sleep. The cadets were divided into three groups, each differing in the amount of sleep and food consumption. The serum levels of thyroid hormones (T4, FT4, T3, rT3) and TBG showed a biphasic pattern during the course. Initially there was an increased secretion concomitant with an increased deiodination of T4 to T3 and rT3 mainly due to physical exercise. When the activities lasted for several days without sufficient food supply the thyroid secretion decreased simultaneously with an alteration of the peripheral conversion of T4 to rT3 instead of T3. A significant correlation was found between the changes in total and free thyroxine (r= 0·9) and between the increase in rT3 and decrease in T3 (r= 0·6). TSH decreased during the first day of activities and remained low throughout the course. The TSH response to TRH stimulation was greatly reduced during the course due to physical exercise and calorie deficiency. The present investigation demonstrates that the thyroid function is strongly affected by prolonged physical exercise and a negative energy balance, whereas sleep deprivation does not have any significant influence. The results indicate that the alteration observed is not regulated just by the hypothalamo‐pituarity‐thyroid‐axis alone.

Secretin—a new stress hormone?

The plasma concentration of secretin was measured during a 5-day military training course comprising prolonged physical exercise (35% of max O2 uptake), severe caloric deficiency (approx. 35700 kJ/24 h) and sleep deprivation (only 2 h of sleep as a total during 5 days). 24 subjects were divided into 3 groups, one group was compensated for the caloric deficiency and another group was partly compensated for the sleep deprivation. The results showed that the fasting plasma secretin increased 3-6-fold (from 1.8-3.7 to 13.3-19.1 pmol/l) during the course with small differences in increase between the groups. Ingestion of a mixed meal reduced the fasting plasma secretin by about 40% during the course, while oral glucose reduced the plasma secretin to the concentrations found in the control experiment. The study shows that plasma secretin is increased when man is exposed to prolonged multifactorial stress. Additional food or sleep appears to have small influence on the fasting plasma secretin, but after giving a meal or oral glucose solution the plasma secretin decreases rapidly.

Granulocyte chemiluminescence response to serum opsonized zymosan particles ex vivo during long-term strenuous exercise, energy and sleep deprivation in humans

The chemiluminescence response of granulocytes to serum opsonized zymosan particles (SOZ) ex vivo was investigated during two ranger training courses lasting 7 days with continuous moderate physical activities corresponding to about 32% of maximal oxygen uptake or 35 000 kJ · 24 h−1, with energy deficiency (energy supply 0-4000 kJ · 24 h−1), and less than 3-h sleep during the 7 days. Significant granulocytosis in combination with a lymphopenia in peripheral blood was observed during the whole course. A priming of the granulocytes for accentuated chemiluminescence response to SOZ was observed during the first days of the course with a maximal increase on day 3 in course A (+35% of control response) and on day 1 in course B (+ 12%). Thereafter, reduced responses to SOZ compared to control values (−28% and −21% in course A and B) were observed. In course A, a group (n = 8) receiving 5000 kJ · 24 h−1 of additional energy, showed a more pronounced priming (maximum +57% versus +21 % of control response) during the first days. In course B, all the cadets had 3 h of organised rest/sleep on day 5, and a second priming of the chemiluminescence response was observed on the subsequent 2 days. These data indicated that moderate, continuous, predominantly aerobic physical activities for 1–3 days around the clock primed the production of reactive oxygen species in granulocytes. This priming may be beneficial for, for example, host defence against micro-organisms, but may also contribute to inflammatory damage to normal tissues such as muscle, tendons and joints during exercise. However, when the moderate exercise continued for several more days, a down-modulation of the granulocyte response was observed. The findings of this study further support the possibility that moderate physical activity stimulates immunity, while more extreme duration of the same activities may result in a down-modulation of nonspecific (and specific) immunity.

Basal hyperchlorhydria and its relation to the plasma concentrations of secretin, vasoactive intestinal polypeptide (VIP) and gastrin during prolonged strain

Twenty young men divided into two groups participated in a five day training course with prolonged and heavy physical exercise, calorie supply deficiency and severe sleep deprivation. Basal acid output (BAO) was measured immediately after the course in seven of ten subjects who were given placebo tablets (placebo group) and in four of ten subjects who had a daily intake of 1 g cimetidine (cimetidine-group) during the course. Median BAO increased 3-fold in the placebo subjects (from 2.7 mmol/h to 8.2 mmol/h) but showed no increase in the cimetidine treated subjects. The median fasting plasma concentrations of secretin increased 2-8-fold during the course. Gastric suction for 1 h or ingestion of cimetidine reduced the plasma concentration of secretin by approx. 50%. Vasoactive intestinal polypeptide (VIP) increased 2-fold and was not influenced by reduction of gastric acid. The placebo group showed a small increase (P less than 0.05) in plasma concentration of gastrin on day two during the course. The study shows a marked hyperchlorhydria which partly explains the fasting hypersecretinemia found during prolonged strain. This strain-induced hyperchlorhydria could be abolished by treatment with the selective H2-receptor antagonist cimetidine.

Effect of short- and long-term physical activities on circulating granin protein levels.

BACKGROUND The classic chromogranin-secretogranin (granin) proteins are produced in the myocardium and throughout the neuroendocrine system, but while chromogranin (Cg) A and B levels are high in the adrenal medulla, secretogranin (Sg) II production is higher in the pituitary gland. Whether these differences may influence the response to physical activity is not known. METHODS We measured circulating granin proteins during (1) a short-term maximal bicycle exercise stress test and (2) a 7 day military ranger course of continuous physical activity and sleep and energy deprivation. RESULTS In 9 healthy subjects performing the exercise stress test (7 male, age 45±5 y [mean±SEM], duration 10.13±1.14 min), CgB levels increased from before to immediately after the test: 1.20±0.12 vs. 1.45±0.09 nmol/L, p=0.013. Metabolic equivalents, representing an index of performed work, were closely associated with the change (∆) in CgB levels during stress testing and explained 74% of the variability in ∆CgB levels (p=0.004). CgA and SgII levels were not increased after exercise stress testing. In the second cohort of 8 male subjects (age 25±1 y) participating in the ranger course, CgB levels increased from day 1 and were significantly elevated on days 5 and 7. CgA also increased gradually with levels significantly elevated on day 7, while SgII was markedly increased on day 5 whereas levels on days 3 and 7 were unchanged compared to baseline levels. CONCLUSION We demonstrate a heterogeneous response to short- and long-term physical activities among circulating granin proteins with the most potent effect on CgB levels.

Plasma renin activity and serum aldosterone during prolonged physical strain

SummaryPlasma renin activity (PRA), serum aldosterone and the serum and urinary levels of sodium and potassium have been investigated in 24 young men participating in a 5-day military training course with heavy continuous physical exercise, energy and sleep deprivation. The subjects were divided into three groups. Group 1 did not get any extra sleep or food, group 2 were compensated for the energy deficiency, and group 3 slept 3 h each night. The basic diet given to all the subjects was about 5,000 kJ and 2 g NaCl·24 h−1·cadet−1. The high calorie diet contained approximately 25,000–35,000 kJ and 20 g of NaCl·24 h−1·cadet−1.The study showed that serum aldosterone and PRA were extremely activated during such prolonged physical strain combined with lack of food and salt, whereas sleep deprivation did not seem to have any large influence. Only small variations were found in the serum levels of sodium and potassium and the urinary level of potassium during the course, whereas a decrease was seen in urinary sodium concentration. The fairly good correlations between the decrease in urinary sodium levels and the increase in PRA (r=0.7) and further between PRA and serum aldosterone (r=0.8) during the course indicate that there is a causal connection between the decrease in urinary sodium excretion and the increase in PRA and serum aldosterone. An increased response was seen during a short term exercise test in groups 1 and 3, whereas no such increase was seen in the subjects of group 2, probably because the higher salt intake abolishes the renin-aldosterone response to exercise. In spite of high catecholamine levels during the course, the serum potassium response to physical exercise was unchanged. The circulating catecholamines did not seem to have any significance for renin secretion and sodium reabsorption during the course. Further, there was no sign of exhaustion in Na/K homeostasis during the experiment.

One week of multifactorial high-stress military ranger training affects Gram-negative signalling

Background. Toll-like receptor 4 (TLR4), especially expressed on monocytes/macrophages, connects microbial and sterile innate immune activation. Lipopolysaccharide (LPS) from Gram-negative bacteria and several endogenous molecules, among others saturated fatty acids (SFAs), are able to induce signalling through this receptor. Downstream inflammatory cytokines orchestrate the immune response. Our aim was to investigate how long-lasting multifactorial stress affects Gram-negative signalling and search for possible correlations between cytokine production and TLR4 expression or SFA concentration. Methods. Eight healthy males were studied during a 7-day ranger-training course with semi-continuous physical strain, together with energy and sleep restrictions. Blood drawn on days 0, 3, 5 and 7 was incubated ex vivo for 6 h with or without LPS 10 ng/mL, whereupon surface expression of TLR4 on CD14+ monocytes and supernatant concentrations of inflammatory cytokines (TNF-α, IL-1β and IL-6) were measured. In addition, plasma free fatty acids were quantified. Results. Monocyte TLR4 expression was elevated throughout the course (p < 0.05 vs. baseline). Corresponding results were found for SFAs. The concentration of TNF-α increased significantly on day 3 and thereafter normalized, and a similar pattern was seen for IL-1β. No correlations were found between cytokine concentrations and monocyte TLR4 expression or plasma SFAs. Conclusion. Multifactorial stress significantly affected ex vivo production of TNF-α and monocyte surface expression of TLR4. In addition, mobilization of fat resulted in increased plasma concentrations of SFAs. No associations between inflammatory cytokines and monocyte TLR4 expression or SFAs were found.

The plasma concentrations of secretin and vasoactive intestinal polypeptide (VIP) after long-term, strenuous exercise

SummaryTwelve subjects (aged 21–38 years) participated in a 90-km cross-country ski race lasting 4.45–6.50 h. In order to investigate a metabolic role for secretin and vasoactive intestinal polypeptide (VIP) during long-term strenuous exercise, seven of the subjects were given an oral hypertonic glucose solution while the others had no nutrient intake immediately after the race. The plasma concentrations of secretin and VIP were greatly increased immediately after the race, and the levels were not normalized within 140 min, though there was a significant decrease after 80 min with rest. The post-race plasma levels of secretin and VIP showed a rapid and very marked decrease 15 min after ingestion of glucose, and the plasma levels had returned to control levels 60 min and 15 min respectively after glucose loading. The results indicate some metabolic function for secretin and VIP during long-term physical exercise.