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.

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.

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.

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.

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.

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.

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.

Maximal heart rate does not limit cardiovascular capacity in healthy humans: insight from right atrial pacing during maximal exercise.

In humans, maximal aerobic power (VO2 max ) is associated with a plateau in cardiac output (Q), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmax on cardiovascular function and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one-legged knee-extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling, Q and leg blood flow increased up to 85% of maximal workload (WLmax) and remained unchanged until exhaustion. SV initially increased, plateaued and then decreased before exhaustion (P < 0.05) despite an increase in right atrial pressure (RAP) and a tendency (P = 0.056) for a reduction in left ventricular transmural filling pressure (LVFP). Atrial pacing increased HRmax from 184 ± 2 to 206 ± 3 beats min(-1) (P < 0.05), but Q remained similar to the control condition at all intensities because of a lower SV and LVFP (P < 0.05). No differences in arterial pressure, peripheral haemodynamics, catecholamines or VO2 were observed, but pacing increased the rate pressure product and RAP (P < 0.05). Atrial pacing had a similar effect on haemodynamics during KEE, except that pacing decreased RAP. In conclusion, the human heart can be paced to a higher HR than observed during maximal exercise, suggesting that HRmax and myocardial work capacity do not limit VO2 max in healthy individuals. A limited left ventricular filling and possibly altered contractility reduce SV during atrial pacing, whereas a plateau in LVFP appears to restrict Q close to VO2 max .

External carotid artery flow maintains near infrared spectroscopy-determined frontal lobe oxygenation during ephedrine administration.

BACKGROUND: Phenylephrine and ephedrine affect frontal lobe oxygenation ([Formula: see text]) differently when assessed by spatially resolved near infrared spectroscopy. We evaluated the effect of phenylephrine and ephedrine on extra- vs intra-cerebral blood flow and on [Formula: see text]. METHODS: In 10 healthy males (age 20-54 yr), phenylephrine or ephedrine was infused for an ∼20 mm Hg increase in mean arterial pressure. Cerebral oxygenation (SavO2) was calculated from the arterial and jugular bulb oxygen saturations. Blood flow in the internal carotid artery (ICAf) and blood flow in the external carotid artery (ECAf) were assessed by duplex ultrasonography. Invos-5100c (SinvosO2) and Foresight (SforeO2) determined [Formula: see text] while forehead skin oxygenation (SskinO2) was assessed. RESULTS: Phenylephrine reduced SforeO2 by 6.9% (95% confidence interval: 4.8-9.0%; P<0.0001), SinvosO2 by 10.5 (8.2-12.9%; P<0.0001), and ECAf (6-28%; P=0.0001), but increased ICAf (5-21%; P=0.003) albeit with no consequence for SskinO2 or SavO2. In contrast, SforeO2 was maintained with administration of ephedrine while SinvosO2 and SavO2 decreased [by 3.1 (0.7-4.5%; P=0.017) and 2.1 (0.5-3.3%; P=0.012)] as arterial carbon dioxide pressure decreased (P=0.003). ICAf was stable and ECAf increased by 11 (4-18%; P=0.005) with administration of ephedrine while SskinO2 did not change. CONCLUSIONS: The effect of phenylephrine on ScO2 is governed by a decrease in external carotid blood flow since it increases cerebral blood flow as determined by flow in the internal carotid artery. In contrast, ScO2 is largely maintained with administration of ephedrine because blood flow to extracerebral tissue increases.

Association between intramuscular fat in the arm following arm training and INSIG2.

Insulin-induced gene 2 (INSIG2) single-nucleotide polymorphism (SNP rs7566605) is linked to lipid metabolism, and this study assessed its potential influence on fat in the upper arm following arm training. Twenty healthy sedentary volunteers (22.0 ± 1.1 years, body mass index 25.4 ± 4.0 kg/m(2) ; mean ± standard deviation) carried out a 12-week two-arm elbow extensor training (10 maximal extensions with 1 min recovery between bouts) five times per day, five times per week. For 17 volunteers, upper arm muscle and adipose tissue [subcutaneous (SCAT) and intramuscular (IMAT)] volumes were evaluated by magnetic resonance imaging before, immediately after, and 12 months after training and variables were related to the subjects' INSIG2 SNP rs7566605 genotype. Muscle volume and SCAT for the upper arm, as the decrease in IMAT during training were not related to INSIG2 SNP rs7566605: GG: %IMAT 1.0 ± 0.9%; GC/CC: %IMAT 0.6 ± 0.5% (P > 0.05). However, in the year following the training, accumulation of upper arm IMAT was twice as large in participants homozygous for the G allele (GG: Δ%IMAT +2.5 ± 0.8%; GC/CC: Δ%IMAT +1.1 ± 0.7%; P < 0.01). This study suggests that the G allele in the INSIG2 SNP rs7566605 is more relevant for changes in IMAT following training than for the amount of subcutaneous fat.

Metabolic and mechanical involvement of arms and legs in simulated double pole skiing.

We evaluated arm and leg work rate and metabolism during double pole ergometer skiing. Thermodilution arm and leg blood flow was determined together with the arterial to venous difference for oxygen, while the work rate was assessed in eight male recreational skiers [24 (SD 7) years]. When work rate increased from 82 (SE 4) to 117 (7) W, leg power increased by 43% (enhanced vertical force and displacement of the body). The elbow angle tended to increase [from 71 (11.3)° to 75 (10.9)°; P = 0.07] and arm oxygen uptake increased by 20 (5)% [from 0.65 (0.07) to 0.78 (0.08) L/min; P < 0.05] because two-arm blood flow increased [from 5.4 (0.6) to 6.3 (0.7) L/min; P < 0.05] with no significant change in oxygen extraction [from 59 (2.3)% to 60 (1.9)%] accompanied with net arm lactate and potassium release. In contrast, two-leg blood flow [from 5.8 (0.5) to 8.0 (0.5) L/min] and oxygen extraction [from 67 (1.3)% to 75 (1.5)%] increased (P < 0.05), resulting in a 53 (8)% increase in leg oxygen uptake [from 0.82 (0.06) to 1.24 (0.07) L/min; P < 0.05]. In conclusion, during double poling on an ergometer, arm muscle metabolism and work rate increase only marginally and an increase in work intensity is covered mainly by the leg muscles.

Peripheral vasodilatation determines cardiac output in exercising humans: insight from atrial pacing.

In dogs, manipulation of heart rate has no effect on the exercise-induced increase in cardiac output. Whether these findings apply to humans remain uncertain, because of the large differences in cardiovascular anatomy and regulation. To investigate the role of heart rate and peripheral vasodilatation in the regulation of cardiac output during steady-state exercise, we measured central and peripheral haemodynamics in 10 healthy male subjects, with and without atrial pacing (100­150 beats min(−1)) during: (i) resting conditions, (ii) one-legged knee extensor exercise (24 W) and (iii) femoral arterial ATP infusion at rest. Exercise and ATP infusion increased cardiac output, leg blood flow and vascular conductance (P < 0.05), whereas cerebral perfusion remained unchanged. During atrial pacing increasing heart rate by up to 54 beats min(−1), cardiac output did not change in any of the three conditions, because of a parallel decrease in stroke volume (P < 0.01). Atrial pacing increased mean arterial pressure (MAP) at rest and during ATP infusion (P < 0.05), whereas MAP remained unchanged during exercise. Atrial pacing lowered central venous pressure (P < 0.05) and pulmonary capillary wedge pressure (P < 0.05) in all conditions, whereas it did not affect pulmonary mean arterial pressure. Atrial pacing lowered the left ventricular contractility index (dP/dt) (P < 0.05) in all conditions and plasma noradrenaline levels at rest (P < 0.05), but not during exercise and ATP infusion. These results demonstrate that the elevated cardiac output during steady-state exercise is regulated by the increase in skeletal muscle blood flow and venous return to the heart, whereas the increase in heart rate appears to be secondary to the regulation of cardiac output.

Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed.

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Orthostatic leg blood volume changes assessed by near-infrared spectroscopy.

Standing up shifts blood to dependent parts of the body, and blood vessels in the leg become filled. The orthostatic blood volume accumulation in the small vessels is relatively unknown, although these may contribute significantly. We hypothesized that in healthy humans exposed to the upright posture, volume accumulation in small blood vessels contributes significantly to the total fluid volume accumulated in the legs. Considering that near-infrared spectroscopy (NIRS) tracks postural blood volume changes within the small blood vessels of the lower leg, we evaluated the NIRS-determined changes in oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total haemoglobin tissue concentration (Δ[tHb]) and in total leg volume by strain-gauge plethysmography during 70 deg head-up tilt (HUT; n = 7). In a second experiment, spatial and temporal reproducibility were evaluated with three NIRS probes applied on two separate days (n = 8). In response to HUT, an initially fast increase in [O(2)Hb] was followed by a gradual decline, while [HHb] increased continuously. The increase in [tHb] during HUT was closely related to the increase in total leg volume (r(2) = 0.95 ± 0.03). After tilt back, [O(2)Hb] declined below and [HHb] remained above baseline, whereas all NIRS signals gradually returned to baseline. Spatial heterogeneity was observed, and for two probes [tHb] was highly correlated between days (r(2) = 0.92 ± 0.09 and 0.91 ± 0.12), but less for the third probe (r(2) = 0.44 ± 0.36). The results suggest a non-linear accumulation of blood volume in the small vessels of the leg, with an initial fast phase followed by a more gradual increase at least partly contributing to the relocation of fluid during orthostatic stress.

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.