Vasomotion in the rat cerebral microcirculation recorded by laser-Doppler flowmetry

In the present study, changes in frequency and amplitude of the rhythmic variations (vasomotion) in blood flow in the intact cerebral circulation of the rat were investigated using laser-Doppler flowmetry (LDF) during stepwise decrease in mean arterial blood pressure (MABP) and hyper-and hypocapnia. Experiments were performed on 12 adult Sprague-Dawley rats of either sex, anaesthetized with α-chloralose. The rat's head was fixed on a stereotaxic frame and a small hole was made in the parietal bone but the dura and a thin inner bone layer were kept intact. The microvascular blood flow of the parietal cortex on the right or on both sides was continuously recorded by the laser-Doppler flowmeter (Periflux PF2B, Perimed, Stockholm, Sweden). The cerebral circulation of the rat exhibited vasomotion in control conditions with a frequency of 8–10 cycles per minute (cpm) and an amplitude of 5–10% of the cerebral blood flow (CBF). No significant changes in CBF could be detected when the MABP was above 60 mmHg, but it decreased significantly when MABP was reduced below 50 mmHg. However, during stepwise pressure reduction the vasomotion frequency decreased progressively while its amplitude showed a reversed U-shaped curve with a peak at 60–80 mmHg. During hypercapnia, the rhythmical oscillations showed a decrease in both frequency and amplitude, whereas during hypocapnia their frequency did not change but their amplitude increased. These results support the hypothesis that the vasomotion frequency might be dependent of the wall tension and cellular pH while its amplitude could be related to decreased tissue oxygenation.     

Vasomotion in the rat cerebral microcirculation recorded by laser-Doppler flowmetry.

In the present study, changes in frequency and amplitude of the rhythmic variations (vasomotion) in blood flow in the intact cerebral circulation of the rat were investigated using laser-Doppler flowmetry (LDF) during stepwise decrease in mean arterial blood pressure (MABP) and hyper- and hypocapnia. Experiments were performed on 12 adult Sprague-Dawley rats of either sex, anesthetized with alpha-chloralose. The rat's head was fixed on a stereotaxic frame and a small hole was made in the parietal bone but the dura and a thin inner bone layer were kept intact. The microvascular blood flow of the parietal cortex on the right or on both sides was continuously recorded by the laser-Doppler flowmeter (Periflux PF2B, Perimed, Stockholm, Sweden). The cerebral circulation of the rat exhibited vasomotion in control conditions with a frequency of 8-10 cycles per minute (cpm) and an amplitude of 5-10% of the cerebral blood flow (CBF). No significant changes in CBF could be detected when the MABP was above 60 mmHg, but it decreased significantly when MABP was reduced below 50 mmHg. However, during stepwise pressure reduction the vasomotion frequency decreased progressively while its amplitude showed a reversed U-shaped curve with a peak at 60-80 mmHg. During hypercapnia, the rhythmical oscillations showed a decrease in both frequency and amplitude, whereas during hypocapnia their frequency did not change but their amplitude increased. These results support the hypothesis that the vasomotion frequency might be dependent of the wall tension and cellular pH while its amplitude could be related to decreased tissue oxygenation.     

Villus tip microcirculation in the rat duodenum

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rev) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rev increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by ～ 10% of the blood volume) reduced rev in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rev in the villus capillaries exposed to abdominal Po₂ (～ 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.     

Short‐term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity

Aim: To determine whether repetitive arm work, with a large component of static muscle contraction alters glucose metabolism and insulin sensitivity. Method: Euglycemic clamps (2 h) were started in ten healthy individuals 15 min after 37 min periods of: (1) repetitive arm work in a simulated occupational setting; (2) dynamic concentric exercise on a cycle ergometer at 60% of VO_2max and (3) a resting regime as a control. During the experimental periods, blood samples were collected, blood pressure was measured repeatedly and electrocardiogram (ECG) was recorded continuously. During the clamps, euglycemia was maintained at 5 mmol l^?1 and insulin was infused at 56 mU m^?2 min^?1 for 120 min. Results: The insulin‐mediated glucose disposal rate (M‐value) for the steady‐state period (60–120 min) of the clamp, tended to be lower following arm work than for both cycling and resting regimes. When dividing the steady‐state period into 20‐min intervals, the insulin sensitivity index (ISI) was significantly lower for arm work compared with the resting control situation between 60–80 min (P = 0.04) and 80–100 min (P = 0.01), respectively. Catecholamines increased significantly for arm work and cycling compared with resting regime. Data from heart rate variability (HRV) measurements indicated significant sympathetic activation during repetitive arm work. Conclusion: The results indicate that repetitive arm work might acutely promote insulin resistance, whereas no such effect on insulin resistance was produced by dynamic concentric exercise.     

Release of neuropeptide Y upon haemorrhagic hypovolaemia in relation to vasoconstrictor effects in the pig

Neuropeptide Y is co-stored with noradrenaline in peripheral sympathetic nerves, but is not present in the adrenal chromaffin cells in the pig. Plasma levels of neuropeptide Y-like immunoreactivity and catecholamines were studied upon haemorrhagic shock in the anaesthetized pig. The animals were bled in two successive steps (30 and 10 ml kg^–), resulting in a reduction of the mean arterial blood pressure by 44% and 53 %, respectively. Plasma levels of noradrenaline increased abruptly after the first bleeding from 1.21 ± 0.27 to 26.5 ± 6.3 nmol 1^-1. Plasma neuropeptide Y showed a progressive increase from 62 ± 8 pmol 1^–1 in the basal state to 365 ± 98 pmol 1^–1 at 60 min after the first bleeding. After the second bleeding plasma neuropeptide Y and noradrenaline showed a largely parallel increase and finally reached levels of 2524 ± 580 pmol 1^–1 and 316 ± 117 nmol 1^–1, respectively. A veno-arterial gradient of neuropeptide Y and noradrenaline indicating local release was present over the spleen after both bleeding steps. The overflow of neuropeptide Y was delayed about 15 min compared to noradrenaline after the initial bleeding. Depletion of the neuropeptide Y content after shock in the heart and skeletal muscle supported local release also from these organs. Infusions of neuropeptide Y to obtain similar plasma concentrations as during shock (nM range) caused reduction in blood flow as determined by the radionuclide-labelled microsphere technique in several organs including spleen and skeletal muscle (threshold response at 319 ± 22 pmol 1^–1) but not in heart and brain. In conclusion, both neuropeptide Y and noradrenaline were markedly elevated in plasma upon haemorrhagic shock, suggesting release from sympathetic nerve terminals. Neuropeptide Y could therefore have a role as a sympathetic neurotransmitter, and during severe stress, circulating plasma levels are in the range where vasoconstriction is evoked by exogenous NPY.     

Calf and shin muscle oxygenation patterns and femoral artery blood flow during dynamic plantar flexion exercise in humans

The effects of dynamic plantar flexion exercise [40, 60, and 80 contractions·min^–1 (cpm)] on calf and shin muscle oxygenation patterns and common femoral artery blood flow ( ) were examined in six female subjects [mean age 21 (SD 1) years] who exercised for 1 min at 33% of their maximal voluntary contraction at ankle angles between 90° and 100°. Spatially resolved near-infrared spectroscopy was used to measure medial gastrocnemius, lateral soleus (synergist) and anterior tibialis (antagonist) muscle oxygen saturation (SO₂, %). was measured by ultrasound Doppler. The SO₂ changed significantly only in the medial gastrocnemius and its decrease (up to about 30%) was independent of the contraction frequencies examined. The increase in , at the end of exercise, was highest at 80 cpm. When the exercise at 60 cpm was prolonged until exhaustion [mean 2.7 (SD 1.1) min], medial gastrocnemius SO₂ decreased, reaching its minimal value [mean 30 (SD 10)%] within the 1st min, and had partially recovered before the end of the exercise with concomitant increases in total haemoglobin content and . These results suggest that the medial gastrocnemius is the muscle mostly involved in dynamic plantar flexion exercise and its oxygen demand with increases in contraction frequency and duration is associated with an up-stream increase in . Electronic Publication     

Beta2-adrenergic attenuation of capillary pressure autoregulation during hemorrhagic hypo tension,a mechanism promoting transcapillary fluid absorption in skeletal muscle

The aim of this study was to evaluate a possible humoral β₂-adrenergic effect on the capillary pressure autoregulation capacity in cat skeletal muscle during bleeding. For this purpose capillary pressure autoregulation in response to graded decrease in arterial pressure was studied in sympathectomized muscle in the control state, and during haemorrhagic hypovolaemia in the presence and absence of selective β₂-adrenoceptor blockade (ICI 118,551). The study was performed with a technique that permits continuous recordings of average capillary pressure in absolute terms and of the regional pre- and postcapillary vascular resistance, from which the pre- to post capillary resistance ratio could be determined. In the pre-haemorrhagic control state, an experimental decrease in arterial pressure from 100 to 50 mmHg caused a fall of capillary pressure from 17.6 by only 1.7 mmHg (ΔP_A/ΔP_c= 29), demonstrating an efficient capillary pressure autoregulation. This autoregulation was accomplished by a decrease in pre- to post capillary resistance ratio in turn being a result of active precapillary dilatation and a passive increase in post capillary vascular resistance. Haemorrhage per se, via a humoral α-adrenergic preferentially precapillary vaso-constriction, caused a decrease in capillary pressure to 16.8 mmHg at arterial pressure 100 mmHg. A superimposed decrease in arterial pressure to 50 mmHg resulted in a capillary pressure fall by 3.7 mmHg (ΔP_A/ΔP_e= 14), indicating impaired autoregulation capacity. This attenuation to a great extent could be ascribed to adrenaline-induced B₂-adrenoceptor stimulation, since β₂-blockade restored the Δ arterial pressure/capillary pressure ratio to 20. Low-dose isoprenaline infusion in the control state similarly caused marked impairment of capillary pressure autoregulation. The β₂-adrenergic attenuation of capillary pressure autoregulation appears to be a beneficial effect in haemorrhagic hypotension, since it lowers capillary pressure passively in relation to the arterial pressure fall, thereby reinforcing the a-adrenergic active capillary pressure decrease, leading to more effective transcapillary fluid absorption and, hence, improved replenishment of plasma volume.     

The role of the adrenal medulla in cardiovascular responses to hypertonic saline in haemorrhaged conscious rats

The aim of this study was to determine if the adrenal medulla plays a role in mediating haemodynamic effects of hypertonic saline (HTS) resuscitation during haemorrhagic hypotension in conscious rats. Wistar-Kyoto rats were either adrenomedullectomized (ADMX, n = 11) or sham-operated (SHAM, n = 10) and implanted with intravascular catheters. Pre-haemorrhage resting mean arterial pressure (MAP) was lower in the ADMX than in the SHAM group. Haemorrhage was performed by withdrawal of blood through the venous catheter, and a MAP of 50 mmHg was maintained for 1 h by further withdrawal when necessary. Both groups responded to haemorrhage with marked bradycardia. Plasma adrenaline (A) rose 10-fold in response to hypotension in the SHAM group, while remaining at pre-haemorrhage levels in the ADMX group, indicating successful adrenal demedullation. Infusion of 2.0 ml kg^-1 HTS (NaCl 8.0 mg ml^-1 i.v.) produced an immediate increase in MAP and heart rate (HR) in both groups, to pre-haemorrhage values or higher. Plasma noradrenaline (NA) increased in both groups after HTS, while the high levels of A in the SHAM group slowly returned toward baseline. Plasma glucose and rate of haemodilution was higher in the SHAM group during and after hypotension. The maintenance of MAP above 60 mmHg was less effective in the SHAM group during the first 2 h after HTS, but after 24 h, pre-haemorrhage MAP was established in both groups. In conclusion, the adrenal medulla does not play a major role in the response to HTS resuscitation.     

Importance of post‐exercise hypotension in plasma volume restoration

The aim of this study was to test the hypothesis that post‐exercise hypotension was the mechanism for the plasma volume and albumin gain during recovery. Seven healthy young men completed two experiments (≥1 week apart) to exercise continuously at 65% of peak aerobic capacity for 60 min followed by the recovery without (experiment 1) or with phenylephrine infusion (experiment 2) to counteract post‐exercise hypotension. Heart rate, arterial pressure (Finapres), plasma volume (PV, Evans blue dye dilution), haematocrit, haemoglobin, plasma total solutes (refractometer), albumin, total proteins (colorimetric method), [Na⁺] and [K⁺] were not different prior to the experiments. Exercise decreased PV –13.7% (–521 mL) and –14.2% (–566 mL) at the end of 60 min in experiments 1 and 2, respectively, associated with increases in the concentrations of plasma albumin, total protein and solutes. These changes were similar between the two experiments. Following 30 min recovery in experiment 1 the decreased PV was not significantly different from the baseline. Although the volume restoration was complete at the end of 90 min recovery, the change in the albumin concentration was still above zero, indicating a gain of 11 g albumin (P < 0.05). When phenylephrine was infused during recovery, there was no gain in intravascular albumin associated with a sustained decrease in PV (–7% or –280 mL, P < 0.05) observed at the end of experiment 2. These data suggest that post‐exercise hypotension may be the mechanism for a gain of intravascular albumin via the lymph return, which enhances plasma water retention and PV restoration during recovery from exercise induced hypovolaemia, even without rehydration.     

Decreased microvascular vasomotion and myogenic response in rat skeletal muscle in association with acute insulin resistance

In addition to increased glucose uptake, insulin action is associated with increased total and microvascular blood flow, and vasomotion in skeletal muscle. The aim of this study was to determine the effect of acute insulin resistance caused by the peripheral vasoconstrictor α-methylserotonin (αMT) on microvascular vasomotion in muscle. Heart rate (HR), mean arterial pressure (MAP), femoral blood flow (FBF), whole body glucose infusion (GIR) and hindleg glucose uptake (HGU) were determined during control and hyperinsulinaemic euglycaemic clamp conditions in anaesthetized rats receiving αMT infusion. Changes in muscle microvascular perfusion were measured by laser Doppler flowmetry (LDF) and vasomotion was assessed by applying wavelet analysis to the LDF signal. Insulin increased GIR and HGU. Five frequency bands corresponding to cardiac, respiratory, myogenic, neurogenic and endothelial activities were detected in the LDF signal. Insulin infusion alone increased FBF (1.18 ± 0.10 to 1.78 ± 0.12 ml min^–1, P < 0.05), LDF signal strength (by 16% compared to baseline) and the relative amplitude of the myogenic component of vasomotion (0.89 ± 0.09 to 1.18 ± 0.06, P < 0.05). When infused alone αMT decreased LDF signal strength and the myogenic component of vasomotion by 23% and 27% respectively compared to baseline, but did not affect HGU or FBF. Infusion of αMT during the insulin clamp decreased the stimulatory effects of insulin on GIR, HGU, FBF and LDF signal and blocked the myogenic component of vasomotion. These data suggest that insulin action to recruit microvascular flow may in part involve action on the vascular smooth muscle to increase vasomotion in skeletal muscle to thereby enhance perfusion and glucose uptake. These processes are impaired with this model of αMT-induced acute insulin resistance.     

Central inhibition of opioid receptor subtypes and its effect on haemorrhagic hypotension in conscious sheep

Aim: To investigate the contribution of cerebral μ‐, κ‐ and δ‐opioid receptors in causing the hypotension, bradycardia and renal hypoperfusion evoked by haemorrhage. Methods: Adult conscious ewes were bled continuously from a jugular vein until mean arterial blood pressure (MAP) was reduced to below 50 mmHg. Starting 30 min before and continuing until 60 min after haemorrhage either artificial cerebrospinal fluid (control), d ‐Phe‐Cys‐Tyr‐d ‐Trp‐Orn‐Thr‐Pen‐Thr‐NH₂ (CTOPμ‐receptor antagonist), ICI 174,864 (δ‐receptor antagonist) or nor‐binaltorphimine dihydrochloride (nor‐BNI, κ‐receptor antagonist) were infused intracerebroventricularly. In a randomized crossover fashion the effect of antagonizing one central opioid receptor subtype was compared to control experiments in the same animal (n = 6 in all groups). Results: Compared to corresponding controls, nor‐BNI and ICI 174,864 significantly increased the haemorrhage volume needed to reduce MAP to below 50 mmHg (+4.7 mL kg^?1, SD 1.8 and +3.1 mL kg^?1, SD 3.0 respectively). In the nor‐BNI group this was accompanied by a significantly augmented tachycardia before MAP fell. Both nor‐BNI and ICI 174,864 also postponed haemorrhagic bradycardia and prolonged adequate blood flow to the kidney. The infusions did not affect the circulation per se or the recovery after haemorrhage. The μ‐opioid receptor blockade had no effect on baseline circulation or the response to haemorrhage. Conclusion: Activation of κ‐ and δ‐opioid receptors adjacent to the ventricular compartment contributes to initiating haemorrhagic hypotension and bradycardia in conscious sheep. However, other parts of the brain and different receptors are likely to play a role as well.     

Clinical and laboratory findings in patients with oliguric and non-oliguric Hantavirus haemorrhagic fever with renal syndrome: an analysis of 128 patients

Patients with haemorrhagic fever with renal syndrome (HFRS) may present without significant oliguria. We compared different initial clinical symptoms and laboratory findings in patients who developed oliguric acute renal failure (ARF) with those in patients who did not develop oliguric ARF. Overall, 128 patients with serologically confirmed HFRS were hospitalized at the University Hospital for Infectious Disease, Zagreb, Croatia between January 1999 and December 2010. Clinical signs and laboratory findings were extracted from medical charts, and were assessed for their relationship to the development of oliguric ARF. Puumala virus infection was diagnosed in 101 (79%) patients, and Dobrava-Belgrade virus infection in 27 (21%). Oliguria or anuria developed in 30% of patients. We identified the following risk factors for the development of oliguria and anuria on multivariable analysis: conjunctival hyperaemia or bleeding (relative risk (RR) 1.84, 95% CI 1.09–3.10; p 0.023), diarrhoea (RR 1.45, 95% CI 1.07–1.97; p 0.017), serum sodium of ≤133 mM (RR 2.21, 95% CI 1.34–3.64; p 0.002), and dipstick protein value of >1.5 g/L (RR 1.59, 95% CI 1.09–2.33; p 0.016), as well as hiking in the forest (RR 1.92, 95% CI 1.13–3.26; p 0.016). Our findings may help physicians in the earlier identification of patients with a more severe form of HFRS caused by Puumala and Dobrava-Belgrade viruses. Particular attention should be given to findings such as conjunctival hyperaemia or bleeding, diarrhoea, a low serum sodium level, and proteinuria.     

M-wave modulation at relative levels of maximal voluntary contraction

Frequency (mean and median power frequency, f and f _m) and amplitude (average rectified and root mean square values, ARV and rms), parameters of the M-wave, and the dorsiflexor force parameters of the anterior tibial muscles were measured in seven healthy human subjects. Intermittent, voluntary contractions at relative intensities (40%, 60%, and 80%) of maximal voluntary contraction (MVC) were performed in conjunction with electrical stimulation. The M-wave parameter changes were measured over the course of the isometric contractions. At higher force levels, M-wave potentiation was observed as increases in both ARV and rms. The ARV augmentation attained levels as high as 206.1 (SD 7.4)% of resting values after both initial and final contractions of 80% MVC, reaching statistical significance (P < 0.01). The f and f _m failed to show a significant difference at any level of contraction. It was surmised that potentiation of the M-wave was the result of an increased contribution of muscle fibre type IIb recruited during higher contraction levels, reflecting the change to larger, deeper innervating motoneurons as the intensity of contraction, as a percentage of MVC, rose. Recruitment of type IIb fibres, which have been reported to have a higher energy potential and frequency content, were thought to reflect changes in the local, excitability threshold of some motor units as the force intensity increased during the intermittent voluntary contractions. It is suggested that the M-wave elicited after contractions has the potential to reflect, to some extent, motor unit recruitment changes resulting from the preceding contractions, and that through comparisons of M-wave amplitude parameters, contributions of varying fibre types over the course of a contraction may be indicated.     

EFFECT OF ANTI-IL-6 AND ANTI-10 MONOCLONAL ANTIBODIES ON THE SUPPRESSION OF THE NORMAL T LYMPHOCYTE MITOGENIC RESPONSE BY STEADY STATE SICKLE CELL DISEASE SERA

Previously published work has shown that sera from healthy sickle cell disease (SCD) patients inhibits normal lymphocyte mitogenic response to phytohemagglutinin (PHA) in vitro. The current study is to attempt to ascertain what effect antibody to type 2 cytokines, interleukin (IL)-6 and 10, have on the suppression of lymphocyte PHA response by SCD sera. Peripheral blood mononuclear cells (PBMC), separated by density gradient were obtained from 2 healthy normal donors. Sera from 50 healthy SCD patients, 50 normal healthy controls and pooled normal O, Rh+ (O+) sera were utilized in standard in vitro PHA stimulation of PBMC cultures. Mitogenic responses were expressed as mean counts per minute (cpm) of triplicate cultures. Fifty triplicate cultures of PHA stimulated normal PBMC were done with 10% normal pooled O+, normal control and SCD steady state sera only. In addition 50 cultures were done with SCD sera containing 1 μg/ml of anti-IL-6 monoclonal antibody, as well as 28 SCD serum cultures containing 1 μg/ml of anti-IL-10 monoclonal antibody. The final 11 SCD serum culture experiments contained a combination of both anti-IL-6 and anti-IL-10 antibody, each at the concentration of 1 μg/ml. Results revealed > 15% suppression of mitogenic response in the SCD sera supplemented cultures as compared to control sera in 47/50 (94%) and in 40/50 (80%) of normal pooled O+, as calculated by mean cpm. The degree of suppression ranged from 17% to 98% in individual experiments. The addition of anti-IL-6 antibody alone significantly improved mean cpm (> 20%) in 19/50 (38%) of SCD serum responses compared to O+ sera and 23/50 (46%) of control sera. Complete correction occurred in 9/50 (18%) of all SCD serum suppressions as compared to O+ sera and 6/50 (12%) when compared to control sera. Similarly, anti-IL-10 antibody decreased suppression of the mean cpm of SCD serum cultures in 18/28 (64%) and completely corrected 3/18 (11%). The combined antibody data revealed > 20% increase in mean cpm in 10/11(91%) experiments. Inhibitors of mitogenic response were present in a significant percentage of the SCD sera utilized in the present study. The significant corrective effects of both monoclonal antibodies would seem to support the original hypothesis that high circulating levels of type 2 cytokines may represent the cell-mediated dependent inhibitory factors expressed in the sera of many healthy SCD patients.     

Nasal heat and water exchange is not an effector mechanism for water balance regulation in grey seals

Phocid seals may effectively restrict respiratory heat and water loss by nasal heat and water exchange (NHE), and respiratory heat loss is, in fact, subject to thermoregulatory control. We have investigated whether phocid seals also control NHE and respiratory water loss to regulate water balance. Three resting juvenile female grey seals (Halichoerus grypus) were subjected to: (i) 5 days of food and water deprivation, (ii) intravenous infusion of 1000 ml of a hyperosmotic (930 mM) solution of the diuretic mannitol, and (iii) oral injection of 1500 ml distilled water. During these experiments in air of 0 ^oC, expired air temperature (T_ex) and respiratory frequency (f) were recorded, and urine and blood samples collected. The results were compared with results from control experiments. Five days of food and water deprivation caused an average 10.5% and 20.8% increase in plasma (PO) and urine (UO) osmolality, respectively. Mannitol infusion induced excessive diuresis and caused an average 2.45% reduction of the estimated body water pool. Water loading caused an average 4.5% and 60% reduction in PO and UO, respectively, while urine production increased by 365%, on average. However, in no case did either T_ex or f change significantly from mean control levels of 22.4 (range: 20.7–25.2) ^oC and 7.3 (range: 6.6–8.4) breaths min“¹, respectively. Thus, water balance disturbances that initiate renal compensatory mechanisms fail to affect NHE in grey seals. This suggests that control of NHE is not an effector mechanism for regulation of water balance in grey seals.     

Brain activation, affect, and aerobic exercise: An examination of both state-independent and state-dependent relationships

Resting electroencephalograph (EEG) asymmetry is a biological marker of the propensity to respond affectively to, and a measure of change in affect associated with, acute aerobic exercise. This study examined the EEG-affect–exercise relationship. Twenty participants performed each of three randomly assigned 30-min conditions: (a) a nonexercise control, (b) a cycling exercise at 55% VO₂max, and (c) a cycling exercise at 70% VO₂max. EEG and affect were assessed pre- and 0, 5, 10, 20, and 30 min postcondition. No significant results were seen in the control or 55% conditions. In the 70% exercise condition, greater relative left frontal activation preexercise predicted increased positive affect and reduced state anxiety postexercise. Participants (n= 7) with extreme relative left frontal activation post-exercise reported concomitant decreases in anxiety, whereas participants (n= 7) with extreme relative right frontal activation postexercise reported increases in anxiety. These findings (a) replicate prior work, (b) suggest a dose-response intensity effect, and (c) support the idea that exercise is an emotion-eliciting event. Affective responses seem to be mediated in part by differential resting levels of activation in the anterior brain regions. Ongoing anterior brain activation reflected concurrent postexercise affect.     

1998 Distinguished Lecture: Biomechanics of the Microcirculation, An Integrative and Therapeutic Perspective

The microcirculation, integratively speaking, is distensible and contains 40%–50% of the total blood volume. Other than the mission of mass transport, the microcirculation and its endothelial cells have the role of regulation, signal transduction, proliferation, and repair. In this article, the emphasis is on the integrative role of the microcirculation on circulatory control and its therapeutic role on blood volume compensation. To introduce this topic, I first summarize the morphometry data on the blood volume distribution in the coronary, pulmonary, and mesentery circulation and then review the methodology developed in my laboratory to assess the microvascular volume change or shift of blood volume from microcirculation to macrocirculation. Evidence obtained through these studies indicates that the microcirculation can play a more important role as a reservoir to compensate for blood volume loss than the venous system. Reanalysis of published data also indicates that microvascular pooling, not hypovolemia, is the likely factor causing endotoxin shock or hypotension for hemodialysis patients. Understanding of the role of the microcirculation could lead to more effective diagnosis of cardiovascular deficiency and therapy for hypotension or low cardiac output with intervention through the microcirculation. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 0110Fv     

A quantitative study of lung dysfunction following haemorrhagic shock in rats

Haemorrhagic shock occasionally causes an episode of lung dysfunction, the severity of which appears to correlate with fatal outcome. Our previous study indicated that proinflammatory cytokines, such as tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β, played a key role in the development of lung dysfunction through recruitment of activated neutrophils by causing pulmonary endothelial cell damage. Here, we examined this issue quantitatively by grading four groups of severity of bleeding in rats. As the amount of bleeding increased, the expression of mRNA for TNF‐α and IL‐1β in the lung tissue and the pulmonary serum levels of both cytokines increased progressively up to 5 h, and the frequency of activated neutrophils increased likewise. The lung dysfunction indices serum lactic dehydrogenase‐3 isozyme (LDH‐3), partial pressure of arterial oxygen (PaO₂) and alveolar‐arterial oxygen tension difference (AaDO₂) in blood deteriorated as the amount of bleeding increased. The frequency of activated neutrophils in the lung correlated well with the LDH‐3 level 5 h after haemorrhagic shock. The present results demonstrate that the increase of proinflammatory cytokines and the recruitment of activated neutrophils into the lung following haemorrhagic shock are quantitatively related to progression of lung dysfunction as the amount of bleeding increases.     

Hyperglycemic and Hyperosmolar Responses to Graded Hemorrhage

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levels and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8, 20, and 25 mOsm/kg H₂O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. — Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.     

Effects of hypertonic NaCl solution on microvascular haemodynamics in normo- and hypovolaemia

The aims of this study were to investigate possible resuscitation effects of a single, 10-min, 350-microliters intravenous infusion of 7.5% NaCl in hamsters in hemorrhagic shock and to compare the effects of such infusion with an identical one of 0.9% NaCl on the hamster cheek pouch microcirculation during normovolaemia and after acute bleeding to a hypotension level of about 40 mmHg. No significant differences could be detected between the effects of either infusion given to normovolaemic normotensive hamsters. In the animals subjected to haemorrhage, upon bleeding, arterioles larger than 40 microns constricted, arterioles smaller than 40 microns dilated and venular diameter did not change, while blood flow decreased in all vessels. The main differences between the infusions after haemorrhage were a significant increase in mean arterial pressure and arteriolar blood flow, venoconstriction and a tendency for the smaller arterioles to remain more dilated and the larger ones more constricted after the hypertonic infusion. Central nervous and/or reflex excitation of the sympathetic nervous system could account for the constriction of venules and larger arterioles, while a direct effect of hyperosmolarity could explain the dilatation of the smaller arterioles. The study can therefore help to explain some of the mechanisms underlying the reported resuscitation effect of 7.5% NaCl infusion in animals during severe haemorrhagic hypovolaemia.