Oxygen uptake, respiratory exchange ratio, or total distance: a comparison of methods to equalize exercise volume in Wistar rats.

This study compared strategies to equalize the volume of aerobic exercise performed with different intensities by Wistar rats, based on the distance covered during exercise bouts and energy expenditure (EE, isocaloric sessions) obtained from oxygen uptake (V̇O2) or respiratory exchange ratio (RER). Thirty-three male rats (270.5±12.8 g) underwent maximal exercise tests to determine V̇O2 reserve (V̇O2R), being randomly assigned to three groups: moderate-intensity continuous exercise at speed corresponding to 50% V̇O2R (MIC; n=11); high-intensity continuous exercise at 80% V̇O2R (HIC; n=11); and high-intensity intermittent exercise (HII; n=11) at 60% V̇O2R (3 min) and 80% V̇O2R (4 min). Exercise duration was calculated individually to elicit EE of 5 kcal in each session. No difference between groups was found for total running distance (MIC: 801±46, HIC: 734±42, HII: 885±64 m; P=0.13). Total EE measured by RER was systematically underestimated compared to values obtained from V̇O2 (HII: 4.5% and MIC: 6.2%, P<0.05). Total EE (calculated from V̇O2), and duration of HIC bouts (2.8 kcal and 30.8±2.2 min) were lower (P<0.0001) than in MIC (4.9 kcal and 64.7±1.8 min) and HII (4.7 kcal and 46.9±2.2 min). Predicted and actual values of total V̇O2, total EE, and duration of isocaloric sessions were similar in MIC and HII (P>0.05), which were both higher than in HIC (P<0.0001). In conclusion, the time to achieve a given EE in exercise bouts with different intensities did not correspond to the total distance. Therefore, the volume of aerobic exercise in protocols involving Wistar rats should be equalized using EE rather than total covered distance.

Oxygen uptake, respiratory exchange ratio, or total distance: a comparison of methods to equalize exercise volume in Wistar rats

This study compared strategies to equalize the volume of aerobic exercise performed with different intensities by Wistar rats, based on the distance covered during exercise bouts and energy expenditure (EE, isocaloric sessions) obtained from oxygen uptake (V̇O2) or respiratory exchange ratio (RER). Thirty-three male rats (270.5±12.8 g) underwent maximal exercise tests to determine V̇O2 reserve (V̇O2R), being randomly assigned to three groups: moderate-intensity continuous exercise at speed corresponding to 50% V̇O2R (MIC; n=11); high-intensity continuous exercise at 80% V̇O2R (HIC; n=11); and high-intensity intermittent exercise (HII; n=11) at 60% V̇O2R (3 min) and 80% V̇O2R (4 min). Exercise duration was calculated individually to elicit EE of 5 kcal in each session. No difference between groups was found for total running distance (MIC: 801±46, HIC: 734±42, HII: 885±64 m; P=0.13). Total EE measured by RER was systematically underestimated compared to values obtained from V̇O2 (HII: 4.5% and MIC: 6.2%, P<0.05). Total EE (calculated from V̇O2), and duration of HIC bouts (2.8 kcal and 30.8±2.2 min) were lower (P<0.0001) than in MIC (4.9 kcal and 64.7±1.8 min) and HII (4.7 kcal and 46.9±2.2 min). Predicted and actual values of total V̇O2, total EE, and duration of isocaloric sessions were similar in MIC and HII (P>0.05), which were both higher than in HIC (P<0.0001). In conclusion, the time to achieve a given EE in exercise bouts with different intensities did not correspond to the total distance. Therefore, the volume of aerobic exercise in protocols involving Wistar rats should be equalized using EE rather than total covered distance.

In elderly women moderate hypercholesterolemia is associated to endothelial and microcirculatory impairments.

How cholesterol influences the microcirculation on aging subjects is not well known. This study evaluated moderate hypercholesterolemia effects in, treated or not, lean elderly women on brachial artery reactivity and microcirculatory function using venous occlusion plethysmography (VOP) and nailfold videocapillaroscopy (NVC). Patients (mean age 73 years) were divided into healthy elderly (HE, n=15), treated dyslipidemia with statins during at least 6 months (TDL, n=9) and dyslipidemia (DL, n=9, cholesterol, 257±11 and LDL-cholesterol, 157±24 mg/dl). Young, mean age 23 years, women (YC, n=24), served as controls. Laboratory and anthropometrical analysis, VOP peak forearm blood flow (FBF) during the reactive hyperemia response/baseline FBF (%HYPER) and peak FBF after 0.4 mg sublingual nitroglycerin/baseline FBF (%NITRO) were assessed. NVC capillary density and diameters, maximum red blood cell velocity (RBCV(max)) during reactive hyperemia/baseline RBCV and time to reach RBCV(max) were evaluated. Correlations between %HYPER, %NITRO and plasma cholesterol fractions were performed. Total and LDL-cholesterol were increased only in DL group. Capillary diameters were larger in elderly groups than YC. RBCV(max)/baseline RBCV was reduced in the DL group compared to HE, TDL and YC. %HYPER was lower in DL and normalized in TDL group. YC %HYPER was double of HE. %NITRO decreased from (HE=YC) to TDL and DL groups. There was a significant inverse correlation between LDL-cholesterol, non-HDL-cholesterol and %HYPER/% Nitro. In conclusion, moderate hypercholesterolemia reversibly impaired the vasodilatatory response in the microcirculation but the endothelial-independent vasodilator response to nitroglycerine remained irreversibly lower in healthy aged women.

Changes on venous diameter and leg perimeter with different clinical treatments for moderate chronic venous disease: evaluation using Duplex scanning and perimeter measurements.

AIM: To evaluate changes on venous diameter and perimeter of lower limbs in chronic venous disorder (CVD) patients after different clinical treatments for four weeks. METHODS: Fifty-two female patients classified as C2,s or C2,3,s (CEAP classification) were allocated consecutively in three groups: Cirkan (40 mg of the root extract of Ruscus aculeatus + 100 mg of flavonoid hesperidine methylchalcone + 200 mg of vitamin C per pill); elastic compression stockings (ECS) and no treatment (NT). Diameters were determined by duplex ultrasound and perimeter with Leg-O-Meter. RESULTS: After treatment, Cirkan significantly decreased popliteal vein and great saphenous vein (GSV) diameters bilaterally and ECS decreased popliteal vein diameter bilaterally and GSV and varices only on the left limb. Perimeters changed only with ECS. Clinical scores changed between Cirkan x NT and ECS x Cirkan. Disability score varied for ECS x NT and Cirkan x NT. chi2 test detected different distribution frequency for C3 and C2 classes according to treatment: ECS (both limbs) and Cirkan (only left limb). Varices and anatomical scores did not change. CONCLUSIONS: ECS emerges as the most effective clinical treatment tested but improvements with Cirkan on vein diameter and CEAP class were also observed. Clinical scores improved due to pain relief and edema reduction (ECS). These findings point to a positive effect of Cirkan, suggesting that venotonic drugs should be taken into account in the treatment of CVD.

Metformin improves skin capillary reactivity in normoglycaemic subjects with the metabolic syndrome.

AIMS: Insulin resistance and a parental history of diabetes mellitus are independently associated with endothelial dysfunction. Oxidative stress has a pivotal role in the pathophysiology of vascular injury. Metformin, in addition to its glucose-lowering properties, has vasculoprotective effects. We investigated whether metformin has beneficial effects on the nutritive skin capillary circulation and deceases oxidative stress in a group at high risk for Type 2 diabetes mellitus (T2DM) and cardiovascular disease. METHODS: Thirty normoglycaemic subjects with the metabolic syndrome (MS),who had first-degree relatives with T2DM, participated. The mean age was 39.1 +/- 8.4 years and body mass index (BMI) 35.7 +/- 4.8 kg/m2 (mean +/- SD). SUBJECTS: were randomized 1 : 1 to receive placebo (n=14) or metformin (n=16; 1700 mg/day) in a double-blind study. At baseline and post treatment, blood and urine samples were collected for biochemical and 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) analysis, respectively. Microcirculation was assessed by nailfold videocapillaroscopy, analysing afferent (AF), efferent (EF) and apical (AP) diameters of capillary loops, functional capillary density (FCD), red blood cell velocity at rest (RBCV), after 1 min arterial occlusion (RBCVmax) and time (TRBCVmax)taken to reach it. RESULTS: Groups did not differ significantly in anthropometric, clinical, laboratory or microvascular measurements at baseline. In the metformin group, weight,BMI, systolic blood pressure and fasting plasma glucose fell, and lipid profile and microcirculatory parameters FCD, AF, EF, AP, RBCVmaxand TRBCVmax improved (all P<0.01). No relationship between clinico-laboratory parameters and microvascular reactivity was observed, except for changes in total and low density lipoprotein-cholesterol and RBCVmax* 8-epi-PGF2alpha did not change significantly in either group. CONCLUSIONS: Metformin improved skin capillary reactivity in normoglycaemic MS subjects independently of significant changes in 8-epi-PGF2alpha levels.

Nailfold videocapillaroscopy in patients with systemic lupus erythematosus.

Nailfold videocapillaroscopy was performed in 21 controls (C) and 21 patients (P) with systemic lupus erythematosus (SLE) classified according to the American College of Rheumatology, with, at least, 1 year of diagnosed disease and having low activity (MEX-SLEDAI) and sequel (SLICC) indexes at the time of the examination, paired by sex and age. Red blood cell velocity (RBCV, mm/s) at rest and after the release of 60s arterial occlusion (RBCVmax, mm/s), time to reach it (TRBCVmax, s), functional capillary density (FCD, number of capillaries /mm2), afferent, apical and efferent capillary diameters (microm) (DAF, DAP and DEF, respectively) were obtained from videotapes analyzed by the CapImage software. The results did not show any significant difference between the groups that were analyzed, suggesting that morphological (capillary diameters) and functional (RBCV, RBCVmax, TRBCVmax and FCD) parameters are not affected by SLE when low activity and sequel indexes of the disease are present.

Nailfold videocapillaroscopy in primary antiphospholipid syndrome (PAPS).

OBJECTIVES: To evaluate microcirculatory changes (functional and morphological) in primary antiphospholipid syndrome (PAPS) patients. METHODS: Thirty-one patients were examined using nailfold videocapillaroscopy (18 PAPS patients and 13 healthy subjects). The patients were subdivided into two subgroups, with lupus anticoagulant (n = 8) and with anticardiolipin (n = 10) antibodies. Capillary morphology was determined; diameters ( micro m) and functional capillary density (FCD, number capillaries/mm2) were measured in control conditions. Blood flow velocity (CBFV, mm/s) was also evaluated at rest and after release of 60 s arterial occlusion. RESULTS: The percentage of subjects with at least one morphological alteration in the observed capillaries was 77.8% for patients and 21.3% for healthy subjects. Capillary diameters ( microm) [afferent (AD), apical (APD) and efferent (ED)] were significantly smaller (mean +/- s.d.: AD-PAPS, 7.4 +/- 2.1; control, 9.1 +/- 2.6, P = 0.063; APD-PAPS, 11.6 +/- 2.3; control, 14.4 +/- 3.8, P = 0.015; ED-PAPS, 8.4 +/- 2.0; control, 10.9 +/- 3.2, P = 0.011) in PAPS patients compared with controls. FCD (PAPS, 8.5 +/- 3.2; control, 8.3 +/- 2.9, P +/- 0.862), mean resting CBFV (PAPS, 0.73 +/- 0.31; control, 0.88 +/- 0.41, P = 0.278), mean peak CBFV after occlusion (PAPS, 1.07 +/- 0.52; control, 1.59 +/- 0.91, P = 0.063) and mean time (s) to reach it (PAPS, 5.2 +/- 1.7; control, 4.6 +/- 1.8, P = 0.101) were not statistically different between the two groups. CONCLUSION: Our results suggest that nailfold capillary morphology is altered in patients with PAPS, but these changes could not be correlated to impairment of functional parameters.

Hyperoxic ventilation at the critical haematocrit.

OBJECTIVE: During normovolaemic haemodilution arterial O(2)-content decreases exponentially. Nevertheless, tissue oxygenation is first maintained initially by increased organ perfusion and O(2)-extraction. As soon as these compensatory mechanisms are exhausted, myocardial ischaemia and tissue hypoxia occur at an individual 'critical' haematocrit (Hct) value. This study was conducted in order to assess whether tissue hypoxia at the critical Hct is reversed by hyperoxic ventilation with 100% O(2). METHOD: Eighteen anaesthetized pigs were ventilated with room air and were hemodiluted by 1:1 exchange of blood with 6% pentastarch to their individual critical Hct (onset of myocardial ischaemia; significant ECG changes). At the critical Hct, hyperoxic ventilation was initiated. In nine complete datasets, global O(2) delivery and consumption, local tissue O(2) partial pressure (tpO(2)) (MDO-Electrode, Eschweiler, Kiel, Germany) and organ blood flow (microsphere method) in skeletal muscle were analyzed at baseline, after haemodilution to the critical Hct and after 15 min of hyperoxic ventilation. RESULTS: At the critical Hct (7.2+/-1.2%), tpO(2) was reduced from 23+/-3 to 10+/-2 Torr with 50% of all values in the hypoxic range (<10 Torr, all P<0.05). During hyperoxic ventilation, contribution of physically dissolved O(2) to the O(2) delivery and O(2) consumption increased by 400 and 563% (P<0.05) and instantly restored tpO(2) to 18+/-2 Torr, (hypoxic values 25%, P<0.05). CONCLUSION: Hyperoxic ventilation reversed tissue hypoxia at the critical Hct due to preferential utilization of plasma O(2) and allowed temporary preservation of tissue oxygenation. During haemodilution, hyperoxic ventilation might offer an effective bridge until red cells are ready for transfusion.

Diaspirin crosslinked hemoglobin enables extreme hemodilution beyond the critical hematocrit.

BACKGROUND: Normovolemic hemodilution is an effective strategy to limit perioperative homologous blood transfusions. The reduction of hematocrit related to hemodilution results in reduced arterial oxygen content, which initially is compensated for by an increase in cardiac output and oxygen extraction ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and tissue hypoxia. OBJECTIVE: To assess whether hemodilution can be extended to lower hematocrit values by the use of a hemoglobin-based artificial oxygen carrier solution. DESIGN: Prospective, randomized, controlled. SETTING: Animal laboratory of a university hospital. SUBJECTS: Twelve anesthetized, mechanically ventilated pigs. INTERVENTIONS: Isovolemic hemodilution was performed with either 10% diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, CO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healthcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%. MEASUREMENTS AND MAIN RESULTS: In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (significant ST-segment depression >0.1 mV and/or arrhythmia). To determine peripheral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue oxygen partial pressure (tPo2, MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventricular (LV) end-diastolic pressure, global and regional myocardial contractility (maximal change in pressure over time, LV segmental shortening, microsonometry method), LV myocardial blood flow (fluorescent microsphere technique), LV oxygen delivery, and the ratio between LV subendocardial and subepicardial myocardial perfusion. In the HSA group, critical hematocrit was found at 6.1 (1.8)% (hemoglobin, 2 g x dL(-1)), whereas all DCLHb-treated animals survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g x dL(-1)) was achieved without signs of hemodynamic instability. Although arterial oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL-1) neither oxygen delivery and oxygen uptake nor median tPo2 and hypoxic tPo2 values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals until 1.2% hematocrit was achieved. This was attributable to a higher coronary perfusion pressure (65 (22) mm Hg vs. 19 (8) mm Hg; p <.05), higher subendocardial perfusion (4.1 (2.6) mL.min-1.g-1 vs. 1.2 (0.4) mL x min(-1) x g(-1)), and subendocardial oxygen delivery (5.7 (2) mL x min(-1) x g(-1), p <.05) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (730); p <.05) and higher regional myocardial contractility (11 (8)% vs. 6 (2)%; p <.05). An increased LV end-diastolic pressure reflected LV myocardial pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted animals. In the DCLHb group, systemic vascular resistance index remained at baseline values throughout the protocol, whereas coronary vascular resistance decreased. In contrast, both variables decreased in HSA-diluted animals. CONCLUSION: DCLHb as a diluent allowed for hemodilution beyond the hematocrit value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). Even at 1.2% hematocrit (hemoglobin, 4.7 g x dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxygenation. This discrepancy in regional oxygenation might be caused by a redistribution of blood flow favoring the heart, which is related to a disproportionate decrease of coronary vascular resistance index during hemodilution with DCLHb.

Three-dimensional visualization of lung blood flow heterogeneity based on fluorescent microsphere technique and fractal dimension: The Blood Flow Analysis System - BFA System.

The heterogeneity of regional pulmonary blood flow (RPBF) can be assessed by fractal analysis. The fractal dimension (FD) is a scale-independent measure of spatial heterogeneity of blood flow. The relative dispersion (RD) is often used to obtain the heterogeneity of RPBF but it is influenced by the resolution of measurement. The Blood Flow Analysis (BFA) System was developed in Delphi to represent the three-dimensional structure of lung blood flow and calculates statistics of FD, RD, spatial correlation of neighbored tissue samples and shows histograms of blood flows at diverse time points during different experiments. The BFA System reads a text file with flows, measured with fluorescent microsphere technique, and constructs the lung anatomy with volumetric pixels showing the flows with a color schema. It is possible to rotate the lungs into two axis (XY) and the statistics are shown with 3D graphics. The System maintains a database with data from various studies at same time. The BFA System was validated with four data sets from previous experiments. The BFA System has shown consistency and it is a new tool to help researchers during lung perfusion studies.

A computational model of ameboid deformation and locomotion.

Traditional continuum models of ameboid deformation and locomotion are limited by the computational difficulties intrinsic in free boundary conditions. A new model using the immersed boundary method overcomes these difficulties by representing the cell as a force field immersed in fluid domain. The forces can be derived from a direct mechanical interpretation of such cell components as the cell membrane, the actin cortex, and the transmembrane adhesions between the cytoskeleton and the substratum. The numerical cytoskeleton, modeled as a dynamic network of immersed springs, is able to qualitatively model the passive mechanical behavior of a shear-thinning viscoelastic fluid (Bottino 1997). The same network is used to generate active protrusive and contractile forces. When coordinated with the attachment-detachment cycle of the cell's adhesions to the substratum, these forces produce directed locomotion of the model ameba. With this model it is possible to study the effects of altering the numerical parameters upon the motility of the model cell in a manner suggestive of genetic deletion experiments. In the context of this ameboid cell model and its numerical implementation, simulations involving multicellular interaction, detailed internal signaling, and complex substrate geometries are tractable.

Decision support system to assist mechanical ventilation in the adult respiratory distress syndrome.

This paper presents a knowledge-based decision support system to assist mechanical ventilation in patients with the Adult Respiratory Distress Syndrome (DSSARDS). The knowledge base uses clinical algorithms developed from interviews and seminars with experts. The system contains 140 rules, applies backward chaining and was built on an IBM-PC compatible microcomputer. Clinical and physiological data and ventilator settings were used for suggestions of ventilatory support mode (VSMODE) and settings (MVSET) and for hemodynamic evaluation and therapy (HEMO). Success rates (s) and kappa coefficient (k) were used to measure agreement between DSSARDS and physicians at 4 decision steps related to: beginning of mechanical ventilation (FIRSTSET), VSMODE, MVSET and HEMO, DSSARDS prototype was evaluated in a development phase with 6 patients aged 48.6 +/- 15.9 years. Agreement results for 142 decision steps were: FIRSTSET k = 0.90, s = 0.93; VSMODE k = 0.76, s = 0.92; HEMO k = 0.58, s = 0.70, MVSET k = 0.86, s = 0.92 (p < 0.05 for all k). Improvements in the knowledge base were performed mainly in HEMO and VSMODE modules. The subsequent test phase studied 5 patients aged 54.8 +/- 11.0 years in a total of 900 decision steps. Results were: FIRSTSET k = 0.93, s = 0.95; VSMODE k = 0.93, s = 0.96; HEMO k = 0.97, s = 0.99, MVSET k = 0.96, s = 0.97 (p < 0.05 for all k). The results indicate significant agreement between DSSARDS and physicians for all decision steps. This suggests that DSSARDS may be used as a support for decision making and a training tool for mechanical ventilation in patients with the adult respiratory distress syndrome.