Biomedical subjects

Niels H Secher

Publications and source records attributed to Niels H Secher.

71 records · Page 4Linked to original sources

PubMed2003

Postural effects on cardiac output and mixed venous oxygen saturation in humans.

The activation of cardiovascular reflexes for postural adaptation questions whether, in healthy humans, the central blood volume is optimised to support the upright position. A functional definition of an 'optimal circulating volume' that provides the heart with enough central blood volume to establish a maximal cardiac output (CO) and mixed venous oxygen saturation (S(v,O2)) at rest was evaluated in nine healthy subjects. Preload to the heart was varied by passively changing the body position from 70 deg head-up to 20 deg head-down tilt. The S(v,O2) was compared with simultaneously measured estimates of CO by computer-controlled thermodilution. The CO was in the range 8.7-3.8 l min(-1) and S(v,O2) was in the range 79-58 %. Neither CO (median 6.0 (range 5.3-8.7) l min(-1)) nor S(v,O2) (mean +/- S.D. 73.6 +/- 2.6 %) changed from the supine to the 20 deg head-down position. During sustained 70 deg head-up tilt, S(v,O2) decreased to 64 +/- 4 % together with a decline in CO to 4.7 (3.9-5.6) l min(-1) (P < 0.05). Under conditions of varying tilt angles, a change in CO is paralleled by concordant changes in S(v,O2). Maximal values for CO and S(v,O2) during supine rest suggest that the horizontal position provides for an 'optimal' central blood volume.

Adaptation, Physiological↗

PubMed2003

Hepatosplanchnic clearance of interleukin-6 in humans during exercise.

The cytokine interleukin (IL)-6 can increase markedly in the circulation during exercise, but whether the liver is a source of this increase is unknown. The aim of this study was to measure IL-6 flux across the hepatosplanchnic tissues in humans. To elevate systemic concentrations of IL-6, six healthy male subjects performed 120 min of semirecumbent cycling, and blood samples were simultaneously obtained from a brachial artery and the hepatic vein before and during exercise for the analysis of IL-6. Hepatosplanchnic blood flow (HBF) was measured using the indocyanine green infusion technique. Net hepatosplanchnic IL-6 balance was calculated from these measures. HBF was 1.3 +/- 0.1 l/min at rest and was not reduced throughout exercise, averaging 1.1 +/- 0.2 l/min. Arterial plasma IL-6 markedly increased (P < 0.05) from 1.8 +/- 0.6 ng/l at rest to 14.3 +/- 3.2 ng/l after 120 min of exercise. The hepatosplanchnic viscera did not contribute to this increase, since there was a net hepatosplanchnic IL-6 uptake (0.8 +/- 0.3 vs. 5.5 +/- 1.9 ng/min, rest vs. 120 min; P < 0.05). These data demonstrate that the hepatosplanchnic viscera remove IL-6 from the circulation in humans. This removal may constitute a mechanism limiting the negative chronic metabolic action of chronically elevated circulating IL-6.

Adult↗

PubMed2003

Syncope, cerebral perfusion, and oxygenation.

During standing, both the position of the cerebral circulation and the reductions in mean arterial pressure (MAP) and cardiac output challenge cerebral autoregulatory (CA) mechanisms. Syncope is most often associated with the upright position and can be provoked by any condition that jeopardizes cerebral blood flow (CBF) and regional cerebral tissue oxygenation (cO(2)Hb). Reflex (vasovagal) responses, cardiac arrhythmias, and autonomic failure are common causes. An important defense against a critical reduction in the central blood volume is that of muscle activity ("the muscle pump"), and if it is not applied even normal humans faint. Continuous tracking of CBF by transcranial Doppler-determined cerebral blood velocity (V(mean)) and near-infrared spectroscopy-determined cO(2)Hb contribute to understanding the cerebrovascular adjustments to postural stress; e.g., MAP does not necessarily reflect the cerebrovascular phenomena associated with (pre)syncope. CA may be interpreted as a frequency-dependent phenomenon with attenuated transfer of oscillations in MAP to V(mean) at low frequencies. The clinical implication is that CA does not respond to rapid changes in MAP; e.g., there is a transient fall in V(mean) on standing up and therefore a feeling of lightheadedness that even healthy humans sometimes experience. In subjects with recurrent vasovagal syncope, dynamic CA seems not different from that of healthy controls even during the last minutes before the syncope. Redistribution of cardiac output may affect cerebral perfusion by increased cerebral vascular resistance, supporting the view that cerebral perfusion depends on arterial inflow pressure provided that there is a sufficient cardiac output.

Cerebrovascular Circulation↗

PubMed2002

Inadequate heat release from the human brain during prolonged exercise with hyperthermia.

Brain temperature appears to be an important factor affecting motor activity, but it is not known to what extent brain temperature increases during prolonged exercise in humans. Cerebral heat exchange was therefore evaluated in seven males during exercise with and without hyperthermia. Middle cerebral artery mean blood velocity (MCA V(mean)) was continuously monitored while global cerebral blood flow (CBF) and cerebral energy turnover were determined at the end of the two exercise trials in three subjects. The arterial to venous temperature difference across the brain (v-aD(temp)) was determined via thermocouples placed in the internal jugular vein and in the aorta. The jugular venous blood temperature was always higher than that of the arterial blood, demonstrating that heat was released via the CBF during the normothermic as well as the hyperthermic exercise condition. However, heat removal via the jugular venous blood was 30 +/- 6 % lower during hyperthermia compared to the control trial. The reduced heat removal from the brain was mainly a result of a 20 +/- 6 % lower CBF (22 +/- 9 % reduction in MCA V(mean)), because the v-aD(temp) was not significantly different in the hyperthermic (0.20 +/- 0.05 degrees C) compared to the control trial (0.22 +/- 0.05 degrees C). During hyperthermia, the impaired heat removal via the blood was combined with a 7 +/- 2 % higher heat production in the brain and heat was consequently stored in the brain at a rate of 0.20 +/- 0.06 J g(-1) min(-1). The present results indicate that the average brain temperature is at least 0.2 degrees C higher than that of the body core during exercise with or without hyperthermia.

Adult↗

PubMed2002

Middle cerebral artery blood velocity during intense static exercise is dominated by a Valsalva maneuver.

Lifting of a heavy weight may lead to "blackout" and occasionally also to cerebral hemorrhage, indicating pronounced consequences for the blood flow through the brain. We hypothesized that especially strenuous respiratory straining (a Valsalva-like maneuver) associated with intense static exercise would lead to a precipitous rise in mean arterial and central venous pressures and, in turn, influence the middle cerebral artery blood velocity (MCA V(mean)) as a noninvasive indicator of changes in cerebral blood flow. In 10 healthy subjects, MCA V(mean) was evaluated in response to maximal static two-legged exercise performed either with a concomitantly performed Valsalva maneuver or with continued ventilation and also during a Valsalva maneuver without associated exercise (n = 6). During static two-legged exercise, the largest rise for mean arterial pressure and MCA V(mean) was established at the onset of exercise performed with a Valsalva-like maneuver (by 42 +/- 5 mmHg and 31 +/- 3% vs. 22 +/- 6 mmHg and 25 +/- 6% with continued ventilation; P < 0.05). Profound reductions in MCA V(mean) were observed both after exercise with continued ventilation (-29 +/- 4% together with a reduction in the arterial CO(2) tension by -5 +/- 1 Torr) and during the maintained Valsalva maneuver (-21 +/- 3% together with an elevation in central venous pressure to 40 +/- 7 mmHg). Responses to performance of the Valsalva maneuver with and without exercise were similar, reflecting the deterministic importance of the Valsalva maneuver for the central and cerebral hemodynamic response to intense static exercise. Continued ventilation during intense static exercise may limit the initial rise in arterial pressure and may in turn reduce the risk of hemorrhage. On the other hand, blackout during and after intense static exercise may reflect a reduction in cerebral blood flow due to expiratory straining and/or hyperventilation.

Adult↗

PubMed2002

Exercise induces hepatosplanchnic release of heat shock protein 72 in humans.

Physical exercise results in the appearance of heat shock protein (HSP) 72 in the circulation that precedes any increase in gene or protein expression in contracting skeletal muscle. In rodents, exercise increases liver HSP72 expression and the hepatosplanchnic viscera are known to release many acute phase proteins. In the present study, we tested the hypothesis that the splanchnic tissue beds release HSP72 during exercise. Seven male subjects performed 120 min of semi-recumbent cycling at 62 +/- 2 % of maximal oxygen uptake. Blood samples were obtained simultaneously from a brachial artery, a femoral vein and the hepatic vein prior to and at 30, 60 and 120 min of exercise. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and hepatosplanchnic blood flow (HBL) was measured using indocyanine green dye. Net leg and net hepatosplanchnic HSP72 balance were calculated as the product of LBF and femoral venous-arterial HSP72 difference and the product of HBF and hepatic venous-arterial HSP72 difference, respectively. Arterial plasma HSP72 was only detected in one subject at rest but progressively appeared in the arterial samples throughout exercise such that at 120 min it was detected in all subjects (0.88 +/- 0.35 pg l(-1); P < 0.05 compared with rest). The contracting muscle did not, however, contribute to this increase since there was no difference in the femoral venous-arterial HSP72 concentration at any time. Rather, the increase in arterial HSP72 was accounted for, at least in part, by release from the hepatosplanchnic viscera with values increasing (P < 0.05) from undetectable levels at rest to 5.2 +/- 0.2 pg min(-1) after 120 min. These data demonstrate that the splanchnic tissues release HSP72 during exercise and this release is responsible, in part, for the elevated systemic concentration of this protein during exercise.

Adult↗

PubMed2002

Interleukin-6 release from the human brain during prolonged exercise.

Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 may be linked with central fatigue, which is enhanced by hyperthermia. Exercise-induced IL-6 may also stimulate hepatic glycogenolysis, which is important during prolonged and repeated exercise. Thus, in a randomised order and separated by 60 min of rest, eight young male subjects completed two 60 min exercise bouts: one bout with a normal (38 degrees C) and the other with an elevated (39.5 degrees C) core temperature. The cerebral IL-6 response was determined on the basis of internal jugular venous to arterial IL-6 differences and global cerebral blood flow. There was no net release or uptake of IL-6 in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 +/- 0.03 ng min(-1)). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 +/- 0.08 ng min(-1); P < 0.05) with no separate influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response.

Adult↗

PubMed2002

The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans.

During and after maximal exercise there is a 15-30 % decrease in the metabolic uptake ratio (O(2)/[glucose + 1/2 lactate]) and a net lactate uptake by the human brain. This study evaluated if this cerebral metabolic uptake ratio is influenced by the intent to exercise, and whether a change could be explained by substrates other than glucose and lactate. The arterial-internal jugular venous differences (a-v difference) for O(2), glucose and lactate as well as for glutamate, glutamine, alanine, glycerol and free fatty acids were evaluated in 10 healthy human subjects in response to cycling. However, the a-v difference for the amino acids and glycerol did not change significantly, and there was only a minimal increase in the a-v difference for free fatty acids after maximal exercise. After maximal exercise the metabolic uptake ratio of the brain decreased from 6.1 +/- 0.5 (mean +/- S.E.M.) at rest to 3.7 +/- 0.2 in the first minutes of the recovery (P < 0.01). Submaximal exercise did not change the uptake ratio significantly. Yet, in a second experiment, when submaximal exercise required a maximal effort due to partial neuromuscular blockade, the ratio decreased and remained low (4.9 +/- 0.2) in the early recovery (n = 10; P < 0.05). The results indicate that glucose and lactate uptake by the brain are increased out of proportion to O(2) when the brain is activated by exhaustive exercise, and that such metabolic changes are influenced by the will to exercise. We speculate that the uptake ratio for the brain may serve as a metabolic indicator of 'central fatigue'.

Adult↗

PubMed2002

[Strategy for peroperative fluid therapy--balancing the central blood volume].

The strategy for preoperative volume treatment is not clear, partly because of the difficulty in monitoring the central blood volume (CBV). The cardiovascular responses to hypovolaemic shock are reviewed with emphasis on the often very low heart rate, which develops when the CBV is reduced by about 30%. A proposal has been put forward that normovolaemia is the CBV that does not limit cardiac output. The possibility of monitoring CBV by electrical impedance is also reviewed. It is concluded that the deviations reflect the CBV accurately in both experimental and clinical studies. A strategy that maintains the CBV ensures cerebral oxygenation even during extensive haemorrhage.

Blood Pressure↗

PubMed2002

Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans.

The development of hyperthermia during prolonged exercise in humans is associated with various changes in the brain, but it is not known whether the cerebral metabolism or the global cerebral blood flow (gCBF) is affected. Eight endurance-trained subjects completed two exercise bouts on a cycle ergometer. The gCBF and cerebral metabolic rates of oxygen, glucose, and lactate were determined with the Kety-Schmidt technique after 15 min of exercise when core temperature was similar across trials, and at the end of exercise, either when subjects remained normothermic (core temperature = 37.9 degrees C; control) or when severe hyperthermia had developed (core temperature = 39.5 degrees C; hyperthermia). The gCBF was similar after 15 min in the two trials, and it remained stable throughout control. In contrast, during hyperthermia gCBF decreased by 18% and was therefore lower in hyperthermia compared with control at the end of exercise (43 +/- 4 vs. 51 +/- 4 ml. 100 g(-1). min(-1); P < 0.05). Concomitant with the reduction in gCBF, there was a proportionally larger increase in the arteriovenous differences for oxygen and glucose, and the cerebral metabolic rate was therefore higher at the end of the hyperthermic trial compared with control. The hyperthermia-induced lowering of gCBF did not alter cerebral lactate release. The hyperthermia-induced reduction in exercise cerebral blood flow seems to relate to a concomitant 18% lowering of arterial carbon dioxide tension, whereas the higher cerebral metabolic rate of oxygen may be ascribed to a Q(10) (temperature) effect and/or the level of cerebral neuronal activity associated with increased exertion.

Adult↗

PubMed2002

Bicarbonate attenuates arterial desaturation during maximal exercise in humans.

The contribution of pH to exercise-induced arterial O2 desaturation was evaluated by intravenous infusion of sodium bicarbonate (Bic, 1 M; 200-350 ml) or an equal volume of saline (Sal; 1 M) at a constant infusion rate during a "2,000-m" maximal ergometer row in five male oarsmen. Blood-gas variables were corrected to the increase in blood temperature from 36.5 +/- 0.3 to 38.9 +/- 0.1 degrees C (P < 0.05; means +/- SE), which was established in a pilot study. During Sal exercise, pH decreased from 7.42 +/- 0.01 at rest to 7.07 +/- 0.02 but only to 7.34 +/- 0.02 (P < 0.05) during the Bic trial. Arterial PO2 was reduced from 103.1 +/- 0.7 to 88.2 +/- 1.3 Torr during exercise with Sal, and this reduction was not significantly affected by Bic. Arterial O2 saturation was 97.5 +/- 0.2% at rest and decreased to 89.0 +/- 0.7% during Sal exercise but only to 94.1 +/- 1% with Bic (P < 0.05). Arterial PCO2 was not significantly changed from resting values in the last minute of Sal exercise, but in the Bic trial it increased from 40.5 +/- 0.5 to 45.9 +/- 2.0 Torr (P < 0.05). Pulmonary ventilation was lowered during exercise with Bic (155 +/- 14 vs. 142 +/- 13 l/min; P < 0.05), but the exercise-induced increase in the difference between the end-tidal O2 pressure and arterial PO2 was similar in the two trials. Also, pulmonary O2 uptake and changes in muscle oxygenation as determined by near-infrared spectrophotometry during exercise were similar. The enlarged blood-buffering capacity after infusion of Bic attenuated acidosis and in turn arterial desaturation during maximal exercise.

Acidosis↗

PubMed2002

Can haemodialysis-induced hypotension be predicted?

BACKGROUND: During haemodialysis (HD) ultrafiltration may affect the central blood volume to an extent that blood pressure decreases. Thoracic electrical impedance (TI) is applied to monitor the central blood volume and we evaluated if it can be used to predict HD-induced hypotension. METHODS: In 12 hypotensive prone (H) and 13 non-hypotensive prone (N) patients, blood pressure and heart rate were recorded during one dialysis session every 30 min, while TI, thoracic intracellular water (Th(ICW)) and total body impedance (TBI) were followed every 10 min. Hypotension was defined as a decrease in systolic blood pressure (SAP) >/=30 mm Hg or a SAP < 90 mm Hg. RESULTS: All 12 H patients developed hypotension after 190 +/- 10 min (mean +/- SE) as SAP decreased 35 +/- 5 mm Hg, while the 13 N patients maintained blood pressure. TBI increased in all patients and the increase was similar (60 +/- 5 and 56 +/- 6 Omega in H and N patients, respectively). In N patients TI did not change significantly for the first 2 h of HD, while it became elevated by 2.8 +/- 0.6 Omega (1.5 kHz) and 2.3 +/- 0.7 Omega (100 kHz) by the end of the dialysis. In H patients, the increase in TI took place at the onset of HD to reach higher values (by 7.0 +/- 0.5 Omega at 1.5 kHz and 5.9 +/- 0.5 Omega at 100 kHz). Th(ICW) was changed only in H patients (decreased by 7.9 +/- 2.1 Siemens (S) 10(-4), p < 0.05), while HR increased (9 +/- 2 beats/min) in 8 of 12 H patients, while it decreased in 1 patient (by 9 beats/min). CONCLUSIONS: The results suggest that in HD patients hypotension is elicited by a reduction in the central blood volume that affects heart rate and the distribution of red cells within the body. To prevent HD-induced hypotention, the ultrafiltration rate could be reduced when an increase in thoracic impedance approaches 5 Omega, or when an index of intracellular water decreases by 6 10(-4).

Blood Pressure↗

PubMed1994

Quantitative sensory examination of epidural anaesthesia and analgesia in man; dose-response effect of bupivacaine.

Time and dose-response functions of 4 concentrations of epidural bupivacaine (0.075, 0.125, 0.25, and 0.5%; 20 ml) on somatosensory and motor functions were examined in 10 healthy volunteers. Every hour for 8 h the effect of epidural bupivacaine on perception of painful and non-painful stimuli was quantified with 12 psychophysical measures. In addition knee extension strength, reaction time and skin temperature were examined. The two lowest concentrations of bupivacaine induced hypoalgesia without impairment of motor function. Epidural bupivacaine produced differential blockade of non-painful somatosensory functions in the following order: warmth perception > cold perception > perception of electrical stimuli. Epidural bupivacaine induced more pronounced hypoalgesia for short-lasting than for prolonged stimuli. A modality-related blocking order was observed for prolonged painful stimuli: heat > mechanical > electrical. It is suggested that differential blockade of somatosensory functions is caused by differences both in conduction blockade of nerve fibres and in central integration of afferent nerve impulses.

Adult↗

PubMed1994

Quantitative sensory examination of epidural anaesthesia and analgesia in man: combination of morphine and bupivacaine.

The effect of epidural administration of a combination of low-dose morphine (2 mg) and bupivacaine (25 mg) on somatosensory and motor functions was examined in 13 healthy volunteers. The study design was a double-blind 4-way cross-over in which combined treatment was compared with either drug used alone or placebo. Every 2nd hour for 10 h effects on nociceptive and non-nociceptive somatosensory functions were quantified with 12 psychophysical measures. In addition knee extension strength, reaction time and skin temperature were examined. Epidural bupivacaine had hypoalgesic effect in all nociceptive tests, whereas epidural morphine only demonstrated hypoalgesic properties in nociceptive test with prolonged stimuli. In comparison with bupivacaine alone the combination treatment had a lesser peak effect but a more prolonged hypoalgesic action. In comparison with morphine alone the combination treatment induced a faster onset and demonstrated a modest increase in hypoalgesic effect in a subset of the test, even beyond the duration of bupivacaine when administered alone. Motor function was not attenuated by any of the treatments. Mechanisms of interaction between morphine and bupivacaine as well as their possible clinical implications are discussed.

Adolescent↗

PubMed1993

Quantitative sensory examination during epidural anaesthesia and analgesia in man: effects of morphine.

In a double-blind placebo-controlled cross-over study the effects of epidural morphine (4 mg) on somatosensory functions were investigated in 10 healthy volunteers. Detection, pain detection and pain tolerance thresholds to thermal, mechanical and electrical stimuli as well as magnitude rating of short-lasting stimuli of the same modalities were monitored before and for 10 h after epidural administration of 4 mg of morphine or saline. Epidural morphine induced a naloxone-reversible (0.1 mg/kg, i.v.) increase in pain detection threshold to heat and mechanical stimuli and in pain tolerance threshold to heat, mechanical and electrical stimuli. Morphine induced a more pronounced increase in the pain tolerance than in the pain detection threshold. Magnitude rating of short-lasting radiant heat (argon laser) stimuli were reduced by epidural morphine in comparison to placebo while there was no significant difference between the effects of morphine and placebo on magnitude rating of short-lasting mechanical and electrical stimuli. The warm detection threshold was increased (naloxone reversible) by morphine. Segmental distribution of pruritus was reported by 7 subjects following epidural morphine which was replaced by a short-lasting burning sensation following naloxone administration. Naloxone (0.1 mg/kg) preceeded by placebo did not change somatosensory functions. These results indicate that the somatosensory effect of epidural morphine is dependent on the types of afferent fibres activated as well as on the duration and intensity of the stimulus.

Adult↗

PubMed1992

Quantitative sensory examination in human epidural anaesthesia and analgesia: effects of lidocaine.

To characterize the sensory effects of epidural lidocaine, 2 groups each of 10 human subjects received 25 ml of 2% lidocaine at the L1-L2/L2-L3 interspace (high lumbar group) or at the L3-L4/L4-L5 interspace (low lumbar group). Twelve quantitative sensory tests in the L5 and S1 dermatomes and leg extension strength were determined every 30 min for 3 h. Sensory and motor blockade were more pronounced in the low than in the high lumbar group. Sensory functions were blocked in the following order by epidural lidocaine: warm > cold > electrical stimuli. Perception of brief localized noxious stimuli was attenuated more than perception of noxious stimuli of longer duration and involving larger stimulus areas. It is suggested that both peripheral mechanisms (differential conduction blockade of afferent fibres) and central mechanisms (temporal and spatial summation) play a role in the sensory effects of epidural lidocaine.

Adult↗

PubMed1992

Plasma and cerebrospinal fluid beta-endorphin in chronic tension-type headache.

Previous studies have provided evidence of an increased sensitivity to pain, a decreased hypothalamic opioid tone, and decreased cerebrospinal fluid (CSF) beta-endorphin (beta-EP) concentration in patients with primary chronic headache. We applied separate specific radioimmunoassays for beta-EP in CSF and plasma on samples from age-matched controls and a group of 50 patients with chronic tension-type headache (CTH) fulfilling the diagnostic criteria set by the International Headache Society. Median CSF beta-EP concentrations (95% confidence limits) were 12.8 pmol/l (11.0-14.5) in CTH patients and 11.9 pmol/l (10.9-14.2) in the control group, which is not significantly different (P = 0.28). Plasma beta-EP concentrations did not differ either, being 3.1 pmol/l (2.4-3.7) and 3.3 pmol/l (1.8-4.0) in the patients with CTH and in controls, respectively (P = 0.88). Plasma and CSF beta-EP concentrations did not correlate. Reversed-phase high performance liquid chromatography (HPLC) of CSF pools from the headache patients and controls revealed similar profiles of beta-EP-immunoreactivity both when C-terminally and N-terminally directed antisera were used, suggesting a normal post-translational processing of the pro-opiomelanocortin gene in patients with CTH. beta-EP is not involved in the pathogenesis of CTH, or such a role is not reflected in CSF or plasma concentrations of the neuropeptide.

Adult↗