Short isocapnic hyperoxia affects indices of vascular remodeling and intercellular adhesion molecules in healthy men.

In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24±3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16±0.85 vs normoxia: 3.51±0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40±3.84 vs normoxia: 5.73±2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53±0.11 vs normoxia: 0.68±0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling.

Short isocapnic hyperoxia affects indices of vascular remodeling and intercellular adhesion molecules in healthy men

In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24±3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16±0.85 vs normoxia: 3.51±0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40±3.84 vs normoxia: 5.73±2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53±0.11 vs normoxia: 0.68±0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling.

Elevated arterial lactate delays recovery of intracellular muscle pH after exercise.

PURPOSE: We evaluated muscle proton elimination following similar exercise in the same muscle group following two exercise modalities. METHODS: Seven rowers performed handgrip or rowing exercise for ~ 5 min. The intracellular response of the wrist flexor muscles was evaluated by 31P nuclear magnetic resonance spectroscopy, while arterial and venous forearm blood was collected. RESULTS: Rowing and handgrip reduced intracellular pH to 6.3 ± 0.2 and 6.5 ± 0.1, arterial pH to 7.09 ± 0.03 and 7.40 ± 0.03 and venous pH to 6.95 ± 0.06 and 7.20 ± 0.04 (P < 0.05), respectively. Arterial and venous lactate increased to 17.5 ± 1.6 and 20.0 ± 1.6 mM after rowing while only to 2.6 ± 0.8 and 6.8 ± 0.8 mM after handgrip exercise. Arterio-venous concentration difference of bicarbonate and phosphocreatine recovery kinetics (T50% rowing 1.5 ± 0.7 min; handgrip 1.4 ± 1.0 min) was similar following the two exercise modalities. Yet, intramuscular pH recovery in the forearm flexor muscles was 3.5-fold slower after rowing than after handgrip exercise (T50% rowing of 2 ± 0.1 vs. 7 ± 0.3 min for handgrip). CONCLUSION: Rowing delays intracellular-pH recovery compared with handgrip exercise most likely because rowing, as opposed to handgrip exercise, increases systemic lactate concentration. Thus the intra-to-extra-cellular lactate gradient is small after rowing. Since this lactate gradient is the main driving force for intracellular lactate removal in muscle and, since pHi normalization is closely related to intracellular lactate removal, rowing results in a slower pHi recovery compared to handgrip exercise.

Pre-operative haemodynamic monitoring and resuscitation in hip fracture patients: Protocol for a prospective observational study.

BACKGROUND: In a frail patient group often suffering from dehydration, hip fracture is potentially fatal partly because of the blood loss and thus deteriorated circulation. An important goal for haemodynamic monitoring and resuscitation is early detection of insufficient tissue perfusion. "The peripheral perfusion index" reflects changes in peripheral perfusion and blood volume. We hypothesize that hip fracture patients are hypovolaemic with poor peripheral perfusion and accordingly respond to controlled fluid resuscitation. The peripheral perfusion index might reflect restricted tissue perfusion in spite of stable central haemodynamic variables. METHODS: This prospective observational study assess to what extend hip fracture patients suffer from hypovolaemia and respond to a stroke volume-guided fluid challenge. The secondary objectives are to evaluate correlation between the non-invasive peripheral perfusion index and minimally invasive measures of stroke volume, changes in blood volume and near-infrared spectroscopy determined tissue- and cerebral oxygenation and to compare results to prevalence of post-operative complications including mortality. We will include 50 patients (>65 years) presenting a hip fracture and treated in a multimodal fast-track regimen when written informed consent is available. DISCUSSION: This is likely the first study to address pre-operative haemodynamic monitoring and resuscitation in hip fracture patients where adequate resuscitation is easily missed. We aim to evaluate feasibility of pre-operative stroke volume-guided haemodynamic optimization in the context of minimally- and non-invasive monitoring of peripheral perfusion and measure of blood volume.

Administration of platelets to ruptured abdominal aortic aneurysm patients before open surgery: a prospective, single-blinded, randomised study.

BACKGROUND: In patients undergoing open surgery for a ruptured abdominal aortic aneurysm (rAAA), survivors demonstrate a high platelet count, and proactive administration of platelets (and fresh frozen plasma) appears to influence mortality. OBJECTIVES: This trial investigated the effect of platelets administered before transport to surgery. METHODS: In a prospective study design, patients were randomised to receive platelets (intervention; n = 61) or no platelets (control; n = 61) before transport to vascular surgery from 11 local hospitals. The study was terminated when one of the vascular surgical centres implemented endovascular repair for rAAA patients. RESULTS: Thirty days after surgery, mortality was 36% for patients with intervention vs 31% for controls (P = 0·32). Post-operative thrombotic events (14 vs 15; P = 0·69), renal failure (11 vs 10; P = 0·15) and pulmonary insufficiency (34 vs 39; P = 0·15) were similar in the two groups of patients. No adverse reactions to platelet administration were observed. In addition, length of stay in the intensive care unit was unaffected by intervention. CONCLUSIONS: For patients planned for open repair of a rAAA, we observed no significant effect of early administration of platelets with regard to post-operative complications and stay in the ICU or in hospital and also no significant effect on mortality.

Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients.

Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release, 1 µmol·min-1·kg leg mass-1), 2) one-legged knee extensor exercise with and without Tyramine infusion [10 W and 20% of maximal workload (WLmax)], 3) ATP (0.05 µmol·min-1·kg leg mass-1) and Tyramine infusion, and 4) incremental ATP infusions (0.05, 0.3, and 3.0 µmol·min-1·kg leg mass-1). We included 10 patients with moderate to severe COPD and 8 age-matched healthy control subjects. Overall, leg blood flow and LVC were lower in COPD patients during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise (COPD: -3 ± 1 ml·min-1·mmHg-1 and controls: -3 ± 1 ml·min-1·mmHg-1, P < 0.05) and 20% WLmax (COPD: -4 ± 1 ml·min-1·mmHg-1 and controls: -3 ± 1 ml·min-1·mmHg-1, P < 0.05) with no difference between groups. Incremental ATP infusions induced dose-dependent vasodilation with no difference between groups, and, in addition, the vasoconstrictor response to Tyramine infused together with ATP was not different between groups (COPD: -0.03 ± 0.01 l·min-1·kg leg mass-1 vs. CONTROLS: -0.04 ± 0.01 l·min-1·kg leg mass-1, P > 0.05). Compared with age-matched healthy control subjects, the vasodilatory response to ATP is intact in COPD patients and their ability to blunt sympathetic vasoconstriction (functional sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP infusion is maintained. NEW & NOTEWORTHY The ability to blunt sympathetic vasoconstriction in exercising muscle and ATP-induced dilation in chronic obstructive pulmonary disease patients remains unexplored. Chronic obstructive pulmonary disease patients demonstrated similar sympathetic vasoconstriction in response to intra-arterial Tyramine during exercise and ATP-induced vasodilation compared with age-matched healthy control subjects.

Severe Postoperative Complications may be Related to Mesenteric Traction Syndrome during Open Esophagectomy.

BACKGROUND: During abdominal surgery, traction of the mesenterium provokes mesenteric traction syndrome, including hypotension, tachycardia, and flushing, along with an increase in plasma prostacyclin (PGI2). We evaluated whether postoperative complications are related to mesenteric traction syndrome during esophagectomy. METHODS: Flushing, hemodynamic variables, and plasma 6-keto-PGF1α were recorded during the abdominal part of open ( n = 25) and robotically assisted ( n = 25) esophagectomy. Postoperative complications were also registered, according to the Clavien-Dindo classification. RESULTS: Flushing appeared in 17 (open) and 5 (robotically assisted) surgical cases ( p = 0.001). Mean arterial pressure was stable during both types of surgeries, but infusion of vasopressors during the first hour of open surgery was related to development of widespread (Grade II) flushing ( p = 0.036). For patients who developed flushing, heart rate and plasma 6-keto-PGF1α also increased ( p = 0.001 and p < 0.001, respectively). Furthermore, severe postoperative complications were related to Grade II flushing ( p = 0.037). CONCLUSION: Mesenteric traction syndrome manifests more frequently during open than robotically assisted esophagectomy, and postoperative complications appear to be associated with severe mesenteric traction syndrome.

Leg blood flow is impaired during small muscle mass exercise in patients with COPD.

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex-matched healthy controls were studied. During knee-extensor exercise (10 W), leg blood flow was lower in the patients compared with the controls (1.82 ± 0.11 vs. 2.36 ± 0.14 l/min, respectively; P < 0.05), which compromised leg oxygen delivery (372 ± 26 vs. 453 ± 32 ml O2/min, respectively; P < 0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the patients with COPD (P < 0.05) and also tended to be higher during exercise (P = 0.07), whereas the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggest that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1.NEW & NOTEWORTHY This study demonstrates that chronic obstructive pulmonary disease (COPD) is associated with a reduced blood flow to skeletal muscle during small muscle mass exercise. In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD.

Muscle oxygen saturation increases during head-up tilt-induced (pre)syncope.

AIM: To evaluate whether muscle vasodilatation plays a role for hypotension developed during central hypovolaemia, muscle oxygenation (Sm O2 ) was examined during (pre)syncope induced by head-up tilt (HUT). Skin blood flow (SkBF) and oxygenation (Sskin O2 ) were determined because evaluation of Sm O2 may be affected by superficial tissue oxygenation. Furthermore, we evaluated cerebral oxygenation (Sc O2 ) and middle cerebral artery mean blood flow velocity (MCAvmean ). METHODS: Twenty healthy male volunteers (median age 24 years; range 19-38) were subjected to passive 50° HUT for 1 h or until (pre)syncope. Sc O2 and Sm O2 (near-infrared spectroscopy), MCAvmean (transcranial Doppler) along with mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) (Modelflow® ) were determined. RESULTS: (Pre)syncopal symptoms appeared in 17 subjects after 11 min (median; range 2-34) accompanied by a decrease in MAP, SV, CO and TPR, while HR remained elevated. During (pre)syncope, Sc O2 decreased [73% (71-76; mean and 95% CI) to 68% (65-71), P < 0.0001] along with MCAvmean [40 (37-43) to 32 (29-35) cm s-1 , P < 0.0001]. In contrast, Sm O2 increased [63 (56-69)% to 71% (65-78), P < 0.0001], while Sskin O2 [64% (58-69) to 53% (47-58), P < 0.0001] and SkBF [71 (44-98) compared to a baseline of 99 (72-125) units, P = 0.020] were reduced. CONCLUSION: We confirm that the decrease in MAP during HUT is associated with a reduction in indices of cerebral perfusion. (Pre)syncope was associated with an increase in Sm O2 despite reduced Sskin O2 and SkBF, supporting that muscle vasodilation plays an important role in the circulatory events leading to hypotension during HUT.

Physiological, biochemical, anthropometric, and biomechanical influences on exercise economy in humans.

Interindividual variation in running and cycling exercise economy (EE) remains unexplained although studied for more than a century. This study is the first to comprehensively evaluate the importance of biochemical, structural, physiological, anthropometric, and biomechanical influences on running and cycling EE within a single study. In 22 healthy males (VO2 max range 45.5-72.1 mL·min-1 ·kg-1 ), no factor related to skeletal muscle structure (% slow-twitch fiber content, number of capillaries per fiber), mitochondrial properties (volume density, oxidative capacity, or mitochondrial efficiency), or protein content (UCP3 and MFN2 expression) explained variation in cycling and running EE among subjects. In contrast, biomechanical variables related to vertical displacement correlated well with running EE, but were not significant when taking body weight into account. Thus, running EE and body weight were correlated (R2 =.94; P<.001), but was lower for cycling EE (R2 =.23; P<.023). To separate biomechanical determinants of running EE, we contrasted individual running and cycling EE considering that during cycle ergometer exercise, the biomechanical influence on EE would be small because of the fixed movement pattern. Differences in cycling and running exercise protocols, for example, related to biomechanics, play however only a secondary role in determining EE. There was no evidence for an impact of structural or functional skeletal muscle variables on EE. Body weight was the main determinant of EE explaining 94% of variance in running EE, although more than 50% of the variability of cycling EE remains unexplained.

Postoperative volume balance: does stroke volume increase in Trendelenburg's position?

In healthy humans, stroke volume (SV) and cardiac output (CO) do not increase with expansion of the central blood volume by head-down tilt or administration of fluid. Here, we exposed 85 patients to Trendelenburg's position about one hour after surgery while cardiovascular variables were determined non-invasively by Modelflow. In Trendelenburg's position, SV (83 ± 19 versus 89 ± 20 ml) and CO (6·2 ± 1·8 versus 6·8 ± 1·8 l/min; both P<0·05) increased, while heart rate (75 ± 15 versus 76 ± 14 b min-1 ) and mean arterial pressure were unaffected (84 ± 15 versus 84 ± 16 mmHg). For the 33 patients (39%) with a > 10% increase in SV (from 78 ± 16 to 90 ± 17 ml) corresponding to an increase in CO from 5·9 ± 1·5 to 6·9 ± 1·6 l min-1 (P<0·05) when tilted head-down, administration of 250 ml Ringer's lactate solution increased SV (to 88 ± 18 ml) and CO (to 6·8 ± 1·7 l min-1 ). In conclusion, determination of SV and/or CO in Trendelenburg's position can be used to evaluate whether a patient is in need of IV fluid as here exemplified after surgery.

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation in men.

Phenylephrine increases mean arterial pressure (MAP) by enhanced total peripheral resistance (TPR) but near-infrared spectroscopy (NIRS) determined muscle oxygenation (SmO2) increases. We addressed that apparent paradox during supine rest and head-up tilt (HUT). Variables were determined ± phenylephrine in males during supine rest (n = 17) and 40° HUT (n = 7). MAP, stroke volume (SV), heart rate (HR), and TPR were derived by Modelflow® and NIRS determined biceps SmO2 and (tibial) bone oxygenation (StibialO2). For ten subjects, cardiac filling and the diameter of the inferior caval vein (ICV collapsibility index: ((ICVexpiration - ICVinspiration)/ICVexpiration) × 100) were assessed by ultrasound. Pancreatic polypeptide (PP) and atrial natriuretic peptide (proANP) in plasma were determined by immunoassay. Brachial artery blood flow was assessed by ultrasound and skin oxygenation (SskinO2) monitored by white light spectroscopy. Phenylephrine increased MAP by 34% and TPR (62%; P < 0.001) during supine rest. The ICV collapsibility index decreased (24%; P < 0.001) indicating augmented cardiac preload although volume of the left atrium and ventricle did not change. SV increased (18%; P < 0.001) as HR decreased (24%; P < 0.001). ProANP increased by 9% (P = 0.002) with unaffected PP. Brachial artery blood flow tended to decrease while SskinO2 together with StibialO2 decreased by 11% (P = 0.026) and 20% (P < 0.001), respectively. Conversely, phenylephrine increased SmO2 (9%) and restored the HUT elicited decrease in SmO2 (by 19%) along with SV (P = 0.02). Phenylephrine reduces skin and bone oxygenation and tends to reduce arm blood flow, suggesting that the increase in SmO2 reflects veno-constriction with consequent centralization of the blood volume.

Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans.

BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise in humans. METHODS: In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato-splanchnic bed (n = 10). RESULTS: In the fasting state, a pronounced release of C2- and C3-carnitines from the hepato-splanchnic bed and an uptake of free carnitine by the legs were detected. Exercise further increased the release of C3-carnitine from the hepato-splanchnic bed and the uptake of free carnitine in the exercising leg. In plasma and in the exercising muscle, exercise induced an increase of most acylcarnitines followed by a rapid decline to preexercise values during recovery. In contrast, free carnitine was decreased in the exercising muscle and quickly restored thereafter. C8-, C10-, C10:1-, C12-, and C12:1-carnitines were released from the exercising leg and simultaneously; C6, C8, C10, C10:1, C14, and C16:1 were taken up by the hepato-splanchnic. CONCLUSION: These data provide novel insight to the organo-specific release/uptake of acylcarnitines. The liver is a major contributor to systemic short chain acylcarnitines, whereas the muscle tissue releases mostly medium chain acylcarnitines during exercise, indicating that other tissues are contributing to the systemic increase in long chain acylcarnitines.

Postural influence on intracranial and cerebral perfusion pressure in ambulatory neurosurgical patients.

We evaluated postural effects on intracranial pressure (ICP) and cerebral perfusion pressure [CPP: mean arterial pressure (MAP) - ICP] in neurosurgical patients undergoing 24-h ICP monitoring as part of their diagnostic workup. We identified nine patients (5 women, age 44 ± 20 yr; means ± SD), who were "as normal as possible," i.e., without indication for neurosurgical intervention (e.g., focal lesions, global edema, abnormalities in ICP-profile, or cerebrospinal fluid dynamics). ICP (tip-transducer probe; Raumedic) in the brain parenchyma (n = 7) or in the lateral ventricles (n = 2) and cardiovascular variables (Nexfin) were determined from 20° head-down tilt to standing up. Compared with the supine position, ICP increased during 10° and 20° of head-down tilt (from 9.4 ± 3.8 to 14.3 ± 4.7 and 19 ± 4.7 mmHg; P < 0.001). Conversely, 10° and 20° head-up tilt reduced ICP to 4.8 ± 3.6 and 1.3 ± 3.6 mmHg and ICP reached -2.4 ± 4.2 mmHg in the standing position (P < 0.05). Concordant changes in MAP maintained CPP at 77 ± 7 mmHg regardless of body position (P = 0.95). During head-down tilt, the increase in ICP corresponded to a hydrostatic pressure gradient with reference just below the heart, likely reflecting the venous hydrostatic indifference point. When upright, the decrease in ICP was attenuated, corresponding to formation of a separate hydrostatic gradient with reference to the base of the skull, likely reflecting the site of venous collapse. ICP therefore seems to be governed by pressure in the draining veins and collapse of neck veins may protect the brain from being exposed to a large negative pressure when upright. Despite positional changes in ICP, MAP keeps CPP tightly regulated.

Near-infrared spectroscopy assessed cerebral oxygenation during open abdominal aortic aneurysm repair: relation to end-tidal CO2 tension.

During open abdominal aortic aneurism (AAA) repair cerebral blood flow is challenged. Clamping of the aorta may lead to unintended hyperventilation as metabolism is reduced by perfusion of a smaller part of the body and reperfusion of the aorta releases vasodilatory substances including CO2. We intend to adjust ventilation according end-tidal CO2 tension (EtCO2) and here evaluated to what extent that strategy maintains frontal lobe oxygenation (ScO2) as determined by near infrared spectroscopy. For 44 patients [5 women, aged 70 (48-83) years] ScO2, mean arterial pressure (MAP), EtCO2, and ventilation were obtained retrospectively from the anesthetic charts. By clamping the aorta, ScO2 and EtCO2 were kept stable by reducing ventilation (median, -0.8 l min(-1); interquartile range, -1.1 to -0.4; P < 0.001). During reperfusion of the aorta a reduction in MAP by 8 mmHg (-15 to -1; P < 0.001) did not prevent an increase in ScO2 by 2 % (-1 to 4; P < 0.001) as EtCO2 increased 0.5 kPa (0.1-1.0; P < 0.001) despite an increase in ventilation by 1.8 l min(-1) (0.9-2.7; P < 0.001). Changes in ScO2 related to those in EtCO2 (r = 0.41; P = 0.0001) and cerebral deoxygenation (-15 %) was noted in three patients while cerebral hyperoxygenation (+15 %) manifests in one patient. Thus changes in ScO2 were kept within acceptable limits (±15 %) in 91 % of the patients. For the majority of the patients undergoing AAA repair ScO2 was kept within reasonable limits by reducing ventilation by approximately 1 l min(-1) upon clamping of the aorta and increasing ventilation by approximately 2 l min(-1) when the lower body is reperfused.

Hypoxia increases exercise heart rate despite combined inhibition of ß-adrenergic and muscarinic receptors.

Hypoxia increases the heart rate response to exercise, but the mechanism(s) remains unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate, but not combined, inhibition of ß-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise to exhaustion in normoxia and hypoxia (fraction of inspired O2 = 12%) after intravenous administration of 1) no drugs (Cont), 2) propranolol (Prop), 3) glycopyrrolate (Glyc), or 4) Prop + Glyc. HR increased with exercise in all drug conditions (P < 0.001) but was always higher at a given workload in hypoxia than normoxia (P < 0.001). Averaged over all workloads, the difference between hypoxia and normoxia was 19.8 ± 13.8 beats/min during Cont and similar (17.2 ± 7.7 beats/min, P = 0.95) during Prop but smaller (P < 0.001) during Glyc and Prop + Glyc (9.8 ± 9.6 and 8.1 ± 7.6 beats/min, respectively). Cardiac output was enhanced by hypoxia (P < 0.002) to an extent that was similar between Cont, Glyc, and Prop + Glyc (2.3 ± 1.9, 1.7 ± 1.8, and 2.3 ± 1.2 l/min, respectively, P > 0.4) but larger during Prop (3.4 ± 1.6 l/min, P = 0.004). Our results demonstrate that the tachycardic effect of hypoxia during exercise partially relies on vagal withdrawal. Conversely, sympathoexcitation either does not contribute or increases heart rate through mechanisms other than ß-adrenergic transmission. A potential candidate is α-adrenergic transmission, which could also explain why a tachycardic effect of hypoxia persists during combined ß-adrenergic and muscarinic receptor inhibition.

Release of erythropoietin and neuron-specific enolase after breath holding in competing free divers.

Free diving is associated with extreme hypoxia. This study evaluated the combined effect of maximal static breath holding and underwater swimming on plasma biomarkers of tissue hypoxemia: erythropoietin, neuron-specific enolase and S100B, C-reactive protein, pro-atrial natriuretic peptide, and troponin T. Venous blood samples were obtained from 17 competing free divers before and 3 h after sessions of static apnea and underwater swimming. The heart was evaluated by echocardiography. Static apnea for 293 ± 78 s (mean ± SD) and subsequent 88 ± 21 m underwater swimming increased plasma erythropoietin from 10.6 ± 3.4 to 12.4 ± 4.1 mIU/L (P = 0.013) and neuron-specific enolase from 14.5 ± 5.3 to 24.6 ± 6.4 ng/mL (P = 0.017); C-reactive protein decreased from 0.84 ± 1.0 to 0.71 ± 0.67 mmol/L (P = 0.013). In contrast, plasma concentrations of S100B (P = 0.394), pro-atrial natriuretic peptide (P = 0.549), and troponin T (P = 0.125) remained unchanged and, as assessed by echocardiography, the heart was not affected. In competitive free divers, bouts of static and dynamic apnea increase plasma erythropoietin and neuron-specific enolase, suggesting that renal and neural tissue, rather than the heart, is affected by the hypoxia developed during apnea and underwater swimming.

Cardiac output during exercise: a comparison of four methods.

Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2 = 12%). While all four methods reported a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0.001] and hypoxia (7.2 ± 0.7, 4.9 ± 0.5, 6.4 ± 0.8 and 5.1 ± 0.4 L/min per L/min; P = 0.04). In hypoxia, the increase in the Q/VO2 slope was not detected by Nexfin. In normoxia, Q increases by 5-6 L/min per L/min increase in VO2, which is within the 95% confidence interval of the Q/VO2 slopes determined by the modified Fick method, Physioflow, and Nexfin apparatus while Innocor provided a lower value, potentially reflecting recirculation of the test gas into the pulmonary circulation. Thus, determination of Q during exercise depends significantly on the applied method.

The hydrostatic pressure indifference point underestimates orthostatic redistribution of blood in humans.

The hydrostatic indifference point (HIP; where venous pressure is unaffected by posture) is located at the level of the diaphragm and is believed to indicate the orthostatic redistribution of blood, but it remains unknown whether HIP coincides with the indifference point for blood volume (VIP). During graded (± 20°) head-up (HUT) and head-down tilt (HDT) in 12 male volunteers, we determined HIP from central venous pressure and VIP from redistribution of both blood, using ultrasound imaging of the inferior caval vein (VIPui), and fluid volume, by regional electrical admittance (VIPadm). Furthermore, we evaluated whether inflation of medical antishock trousers (to 70 mmHg) affected HIP and VIP. Leaving cardiovascular variables unaffected by tilt, HIP was located 7 ± 4 cm (mean ± SD) below the 4th intercostal space (IC-4) during HUT and was similar (7 ± 3 cm) during HDT and higher (P < 0.0001) than both VIPui (HUT: 22 ± 16 cm; HDT: 13 ± 7 cm) and VIPadm (HUT: 29 ± 9 cm; HDT: 20 ± 9 cm below IC-4). During HUT antishock trousers elevated both HIP and VIPui [to 3 ± 5 cm (P = 0.028) and 17 ± 7 cm below IC-4 (P = 0.051), respectively], while VIPadm remained unaffected. By simultaneous recording of pressure and filling of the inferior caval vein as well as fluid distribution, we found HIP located corresponding to the diaphragm while VIP was placed low in the abdomen, and that medical antishock trousers elevated both HIP and VIP. The low indifference point for volume shows that the gravitational influence on distribution of blood is more profound than indicated by the indifference point for venous pressure.