Dynamic changes in organ blood flow and oxygen consumption during acute asphyxia in fetal sheep

The effects of acute asphyxia on both the time course of blood flow changes in central and peripheral organs, including the skin, and the time course of changes in oxygen consumption were studied in 9 unanaesthetized fetal sheep in utero at 130 +/- 2 days of gestation during 4-min arrest of uterine blood flow. Blood flow distribution and total oxygen consumption were determined at 1-min intervals during asphyxia using isotope-labelled microspheres (15 micrograms diameter) and by calculating the decline of the arterial O2 content, respectively. During asphyxia peripheral blood flow including that to the skin, scalp, and choroid plexus decreased rapidly, whereas blood flow to the heart, brain stem and (in surviving fetuses only) adrenals increased slowly. Total oxygen consumption fell exponentially with time and was closely correlated with the fall in both arterial oxygen content and peripheral blood flow; the time courses of these changes were very similar to those of the decreasing blood flows to the skin and scalp. Blood flow within the brain was redistributed at the expense of the cerebrum and the choroid plexus; the total blood flow to the brain did not change. In the 5 fetuses that died during the recovery period adrenal blood flow failed to increase and, at the nadir of asphyxia, peripheral vessels dilated and central vessels constricted. We conclude that in fetal sheep near term during acute asphyxia the time course of changes in blood flow to central and peripheral organs is different; total oxygen consumption depends on arterial O2 content and peripheral blood flow; total blood flow to the brain does not change, but is redistributed towards the brain stem at the expense of the cerebrum and choroid plexus; fetal death is preceded by a failure of adrenal blood flow to increase, by peripheral vasodilatation, and by central vasoconstriction and skin blood flow validly indicates rapid changes in the distribution of blood flow and the changes in oxygen consumption that accompany it.     

壬基酚对黑斑蛙的毒性效应

通过研究壬基酚对黑斑蛙(Rana nigromaculata)血浆渗透压以及血细胞的影响,探讨壬基酚对黑斑蛙血液的毒性效应。用200、400和600mg/kg壬基酚分别对黑斑蛙腹部淋巴囊注射染毒,在不同的时间间隔内利用渗透压仪测量各组血浆渗透压,同时制作血涂片观察血细胞的异常现象。结果表明,在相同处理时间内,随着壬基酚浓度的增加,黑斑蛙血浆渗透压值上升,血细胞膨大,血细胞核分裂以及核质不均匀现象明显;在相同浓度处理组中,随着处理时间的延长,黑斑蛙血浆渗透压上升,血细胞膨大,细胞核损害严重。壬基酚可诱发红细胞出现微核现象,随着壬基酚浓度的增加,同一处理时间内黑斑蛙红细胞微核及核异常率呈现先上升后下降的变化规律;随着处理时间的延长,各处理组红细胞微核率及核异常率呈现下降的趋势。     

Effects of lung inflation and blood flow on capillary transit time in isolated rabbit lungs.

In a previous study, direct measurements of pulmonary capillary transit time by fluorescence video microscopy in anesthetized rabbits showed that chest inflation increased capillary transit time and decreased cardiac output. In isolated perfused rabbit lungs we measured the effect of lung volume, left atrial pressure (Pla), and blood flow on capillary transit time. At constant blood flow and constant transpulmonary pressure, a bolus of fluorescent dye was injected into the pulmonary artery and the passage of the dye through the subpleural microcirculation was recorded via the video microscope on videotape. During playback of the video signals, the light emitted from an arteriole and adjacent venule was measured using a video photoanalyzer. Capillary transit time was the difference between the mean time values of the arteriolar and venular dye dilution curves. We measured capillary transit time in three groups of lungs. In group 1, with airway pressure (Paw) at 5 cmH2O, transit time was measured at blood flow of approximately 80, approximately 40, and approximately 20 ml.min-1.kg-1. At each blood flow level, Pla was varied from 0 (Pla less than Paw, zone 2) to 11 cmH2O (Pla greater than Paw, zone 3). In group 2, at constant Paw of 15 cmH2O, Pla was varied from 0 (zone 2) to 22 cmH2O (zone 3) at the same three blood flow levels. In group 3, at each of the three blood flow levels, Paw was varied from 5 to 15 cmH2O while Pla was maintained at 0 cmH2O (zone 2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors involved in ethanol narcosis: analysis in mice of three inbred strains

We have studied the effects of genotype and dose on the time of onset of ethanol-induced sleep, as measured by fall time, and on the length of sleep. We have also investigated the relationships among genotype, dose and the blood ethanol levels at time of fall and time of awakening in three inbred mouse strains (C57BL/6J, DBA/2J and BALB/cJ). The sleep-time dose response curves are linear for the dose range tested in all three strains. There was no significant linear correlation between dose and blood ethanol level at awakening in any of the three strains. Between-strain comparisons showed significant differences in rate of ethanol clearance from the blood, and differences in tissue sensitivity to ethanol among the strains were demonstrated. Our data suggest that the major factor influencing sleep time is blood alcohol clearance, reflecting differences in alcohol metabolic rates.Between-strain comparisons of fall time showed significant differences, over the dosage range tested, in nervous system tissue sensitivity (as inferred from blood alcohol level at time of fall) between the BALB/cJ strain and the C57BL/6J and DBA/2J strains. Differences between C57BL/6J and DBA/2J strains were significant only at the lowest dose tested. The rank-ordering of the strains with respect to tissue sensitivity to ethanol is identical for all three tissue sensitivity measures obtained in these experiments.     

Microcomputer monitor and blood sampler for free-diving Weddell seals

The equipment used for the first sampling of arterial blood at depth on free-diving Weddell seals Leptonychotes weddelli is described. Blood was withdrawn through an aortic catheter by a submersible, peristaltic roller pump and stored in a single- or multiple-sample collection device. The multiple sampler allowed up to eight individual blood samples to be collected during a single dive. The blood pump was controlled by a dedicated microcomputer that allowed initiation of blood sampling at flexible combinations of depth and/or time during either the descending or ascending phase of the dive. The dedicated microcomputer also recorded swimming depth, velocity, heart rate, and body temperature at selectable time intervals. These data were transmitted to a laboratory computer, and blood samples were retrieved, when the seal surfaced to breathe.     

Platelet Adhesiveness after Blood Donation

Platelet adhesiveness to glass was measured in healthy blood donors at the time of and eight days after donating 500 ml of blood. By a whole blood method a highly significant increase was found whereas by a method using platelet-rich plasma with added adenosine diphosphate there was only a slightly significant increase. The discrepancy suggested that changes in the red cell population might influence the results. Packed red cells from 19 blood donors obtained at the time of donation and eight days later were mixed with fresh pooled platelets from the same independent persons on each occasion. The whole blood platelet adhesiveness on this mixture showed an increase in every case after blood donation. It is postulated that the increased adhesiveness is influenced by the presence of young red cells.     

Vagus nerve is involved in lack of blood reflow into sinusoids after rat hepatic ischemia

Although recovery of microcirculation is an important determinant for ischemia-reperfusion injury, little information is available about hepatic blood flow after ischemia. To examine regulatory mechanisms of postischemic hepatic microcirculation, we studied the sinusoidal blood flow after portal triad clamping of rat livers for 5, 15, or 30 min. Hepatic tissue blood flow and erythrocyte blood flow in sinusoids were measured using a laser-Doppler flowmeter and an intravital microspectroscope, respectively. There was a time of no blood flow (lag time) in sinusoids after declamping, dependent on the ischemic time. Cholinergic blockade agents eliminated the lag time, whereas nerve stimulation at the hiatus esophagus or on the hepatoduodenal ligament during reperfusion prolonged it. Chemical denervation with 10% phenol or surgical denervation on the hepatoduodenal ligament eliminated the lag time. The prolongation of lag time by nerve stimulation was completely abrogated by truncal vagotomy. These results suggest that the cholinergic vagus nerve is involved in causing the lag time of sinusoidal blood flow in hepatic ischemia-reperfusion.     

Continual measurement of intramedullary blood perfusion with laser Doppler flowmetry in intact and ostectomized tibiae of rabbits

Blood flow is important for the healing of bone fractures. Until now, however, there have been no publications on the daily, continual measurement of intramedullary blood perfusion using laser Doppler flowmetry (LDF) in the conscious animal. In this study, a model for the daily, continual measurement of intramedullary blood perfusion by LDF and the temperature near the cortex both in intact and ostectomized tibiae in the conscious rabbit is described. The probes for blood perfusion and temperature measurement were implanted permanently at three different localizations into the right tibia of 10 adult New Zealand White rabbits. The probes were held in place by a bilateral, single-plane external fixator. In five of these animals, a midshaft tibial ostectomy was created in order to simulate a fracture. Intramedullary blood perfusion and temperature were measured daily over 49 days. While in intact tibiae no significant (P > 0.05) differences were found in blood perfusion readings taken at various time points, for mean values or for blood perfusion over time, in ostectomized tibiae the differences were significant: various time points (P = 0.0056), mean values (P = 0.0034) and blood perfusion over time (P = 0.0337). Blood perfusion readings at the centre probe were elevated compared with those at the proximal and distal probes. Thus, a revascularization in the ostectomy gap during the fracture healing was proven by means of the LDF. No influence of the blood perfusion on the temperature in the ostectomy area could be determined during healing of the ostectomy. The described model seems suitable for the continual measurement of intramedullary blood perfusion both in intact and ostectomized tibiae in the conscious rabbit.     

The age factor in blood flow in the calf and in vascular resistance at rest and in reactive hyperaemia.

The blood flow and vascular resistance in the calf were studied in two groups of healthy subjects (mean ages 22 and 49 years) at rest and in reactive hyperaemia produced by five minutes' ischaemia of the lower limb. The blood flow was determined by venous occlusive plethysmography and vascular resistance was computed from the mean blood pressure measured by auscultation on the arm and from the blood flow in the calf, at rest and during reactive hyperaemia. The resting flow and blood flows throughout practically the whole time of hyperaemia were found to be significantly smaller in young individuals. The maximal flow was significantly lower, the maximal flow time was significantly prolonged in young subjects. The recovery time and repayment of the flow debt in the two groups were the same. Vascular resistance in the calf was significantly greater in young subjects, both at rest and during dilatation. We assume from the results that the capacity of the arterial system in the lower limbs is significantly smaller in young individuals.     

Diurnal Profiles of Blood Glucose in Relation to Time of Administration of Melatonin in Male Spotted Munia (Lonchura punctulata)

The study was aimed at demonstration of the effect of a single acute dose of melatonin (0.5 mg/ 100 g body wt.) on the diurnal profile of blood glucose in male spotted munia in relation to the administration of hormone at the onset of light (i.e., at 06.00 h) or at the onset of darkness (i.e., at 18.00 h) under natural photoperiodic (~12L : 12D) conditions. Blood samples from all birds belonging to the control, sham-control (administered only with the vehicle of hormone, i.e., ethanol-saline 1:9 v/v), and melatonin treated groups were collected at four time points, i.e. 06.00 h, 12.00 h, 18.00 h, and 24.00 h, in a 24 hour cycle. The blood glucose levels in control and sham-control birds showed marked variation with regard to the time of sampling, with a mid-day peak and morning nadir. Exogenous melatonin induced a significant alteration in this diurnal pattern of blood glucose with a marked variation in relation to the time of administration of melatonin. While morning administration of melatonin resulted in hypoglycemia at 12.00 h and 24.00 h and hyperglycemia at 18.00 h, the response to evening injection of melatonin was only hypoglycemic at 24.00 h leaving the glycemic values at other time-points almost unaltered compared to the blood glucose levels in control and sham-control munias. The results of this investigation demonstrate for the first time that a schedule of morning administration of melatonin induces a more broad range of variations in the blood glucose levels than a schedule of evening administration does.     

Effect of holding time and temperature of bovine whole blood on concentration of progesterone, estradiol-17beta and estrone in plasma and serum samples

Bovine jugular venous blood was collected, with and without heparin, and aliquoted into 140 12-ml tubes. Four subsamples (two heparinized and two coagulated) were centrifuged immediately (time zero) and plasma or serum was aspirated and stored at -20 degrees C. One-half of the remaining subsamples were stored at 4 degrees C and the other one-half at 25 degrees C (room temperature). At 1-h intervals (0 to 24 h), 6-h intervals (24 to 72 h) and at 96 and 120 h, four subsamples (heparinized and coagulated at both 4 degrees C and 25 degrees C) were centrifuged, plasma or serum was aspirated and stored at -20 degrees C. Whole blood incubation for 1 h at 25 degrees C reduced mean plasma and serum progesterone (P(4)) concentration (P<0.05). Similarly, whole blood incubation at 4 degrees C for 2 and 3 h, respectively, reduced mean plasma and serum P(4) concentration (P<0.05). No difference was found in mean P(4) concentration between plasma and serum samples harvested from whole blood incubated at 4 degrees C or 25 degrees C. Concentration of estradiol-17beta (E(2)) and estrone (E(1)) fluctuated over time, irrespective of holding temperature. There was a blood type, heparinized or coagulated, by time interaction (P<0.01) for both E(2) and E(1) concentrations It was concluded that incubation time and temperature between collection and centrifugation of bovine blood samples influenced the assayable P(4) concentration in both plasma and serum. In contrast, incubation temperature had no effect on assayable E(2) and E(1) concentrations, but assayable E(2) and E(1) over time were differentially affected, depending on whether plasma or serum was assayed.     

Diurnal Profiles of Blood Glucose in Relation to Time of Administration of Melatonin in Male Spotted Munia (Lonchura punctulata)

The study was aimed at demonstration of the effect of a single acute dose of melatonin (0.5 mg/ 100 g body wt.) on the diurnal profile of blood glucose in male spotted munia in relation to the administration of hormone at the onset of light (i.e., at 06.00 h) or at the onset of darkness (i.e., at 18.00 h) under natural photoperiodic (~12L : 12D) conditions. Blood samples from all birds belonging to the control, sham-control (administered only with the vehicle of hormone, i.e., ethanol-saline 1:9 v/v), and melatonin treated groups were collected at four time points, i.e. 06.00 h, 12.00 h, 18.00 h, and 24.00 h, in a 24 hour cycle. The blood glucose levels in control and sham-control birds showed marked variation with regard to the time of sampling, with a mid-day peak and morning nadir. Exogenous melatonin induced a significant alteration in this diurnal pattern of blood glucose with a marked variation in relation to the time of administration of melatonin. While morning administration of melatonin resulted in hypoglycemia at 12.00 h and 24.00 h and hyperglycemia at 18.00 h, the response to evening injection of melatonin was only hypoglycemic at 24.00 h leaving the glycemic values at other time-points almost unaltered compared to the blood glucose levels in control and sham-control munias. The results of this investigation demonstrate for the first time that a schedule of morning administration of melatonin induces a more broad range of variations in the blood glucose levels than a schedule of evening administration does.     

Changes in porcine,ovine, bovine and equine blood progesterone concentrations between collection and centrifugation

The aim of this study was to determine if different methods of handling porcine, ovine, bovine and equine blood between collection and centrifugation influence measurable progesterone levels. A 2 × 2 × 5 factorial experiment was conducted for each species with heparin (with or without), temperature of incubation (4 and 22°C) and time of incubation (0, 6, 12, 24 and 48 h) as the main effects. Following centrifugation, plasma and serum samples were stored at ?20°C until progesterone concentrations were determined by radioimmunoassay. Method of handling porcine and equine blood between collection and centrifugation did not affect the levels of progesterone. However, heparinized blood held at 4°C resulted in the most consistent levels of progesterone over time. Progesterone levels were fairly consistent across time in the ovine blood by all methods of handling except heparinized blood incubated at 22°C. By 24 h after collection, plasma progesterone concentrations decreased by 50% for the ovine blood incubated at 22°C with heparin. Decreases were detected by all the methods of handling the bovine blood between collection and centrifugation. The rate of decline, however, was considerably faster for blood held at 22°C than blood held at 4°C. At 12–48 h after collection, the concentrations of progesterone averaged only 5% of the time 0 sample for blood incubated at 22°C. In contrast, at least 30% of the progesterone values in the time 0 sample were detected between 12 and 48 h of incubation for the blood held at 4°C.     

Time course for recovery of peak aerobic power after blood donation

Peak aerobic power (VO2peak) is decreased after blood donation, but the time course for full recovery is unknown. We measured VO2peak and exercise time to fatigue before and weekly for 4 weeks after 450-ml blood donation at a blood donor clinic, to determine the time course of recovery. Twelve moderately active individuals (2 women, 10 men; 24.3 ± 5.2 years) of average aerobic fitness (based on their VO2peak relative to normative values) completed VO2peak exercise tests before donation, the day after donation, and at weekly intervals for 4 weeks after donation. VO2peak was determined by an incremental exercise test on a cycle ergometer. At baseline, mean absolute and relative VO2peak values were 4.06 ± 0.92 L·min(-1) and 46.6 ± 7.0 ml·kg(-1)·min(-1), respectively. VO2peak was significantly decreased on day 1 (3.85 ± 0.89 L·min(-1); 44.0 ± 6.5 ml·kg(-1)·min(-1)) and during week 2 (3.91 ± 0.97 L·min(-1); 44.5 ± 7.2 ml·kg(-1)·min(-1)) after blood donation (p < 0.05), and recovered at week 3 after donation. Time to fatigue and peak heart rate were not significantly affected by blood donation. We conclude that blood donation causes a significant decrease in VO2peak for between 2 and 3 weeks. The practical application of this study is that aerobic power in people of average fitness will be decreased, up to 3 weeks after donating blood. Despite this, there is no effect of blood donation on performance as measured by time to fatigue during an incremental test on a cycle ergometer.     

Blood lactate responses in older swimmers during active and passive recovery following maximal sprint swimming

The purpose of this study was to determine the effect of age on three blood lactate parameters following maximal sprint swimming. The parameters examined were maximal blood lactate concentration, time to reach maximal blood lactate concentration, and half recovery time to baseline lactate concentration. These parameters were examined in 16 male competitive masters swimmers (n = 4 for each age group: 25-35, 36-45, 46-55, and 56 plus years) during both passive and active recovery following a maximal 100 m freestyle sprint. Passive recovery consisted of 60 min sitting in a comfortable chair and active recovery consisted of a 20-min swim at a self-selected pace. Capillary blood samples were obtained every 2 min up to 10 min of recovery then at regular intervals to the end of the recovery period. Curves of blood lactate concentration against time were drawn and the three parameters determined for each condition for each subject. There were no significant differences between age groups in any of the lactate parameters examined. A significant difference (P less than 0.05) was noted in each of the parameters between active and passive recovery over all age groups. As expected, active recovery produced lower maximal blood lactate concentrations, lower time to maximal blood lactate values, and lower half recovery times. These data suggest that intensive swimming training may prevent or delay the decline with age in the physiological factors affecting blood lactate values following a maximal sprint swim. Older sprint swimmers appeared to be capable of producing and removing lactic acid at the same rate as younger swimmers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pre-analytical handling on haematological variables in minipigs

Pre-analytical handling may be an important determinant of haematological variables, if analysis is delayed. We investigated the effect of anticoagulants, i.e. tripotassium ethylenediamine-tetraacetic acid (EDTA) and citric acid, theophylline, adenosine, dipyridamole (CTAD), storage time (0.5, 1.5, 3.5, 5.5, 7.5, 25.5 and 27.5 h after blood sampling), and storage temperature (5 degrees C and 20 degrees C) on the variation in haemoglobin (HGB), red blood cell count (RBC), haematocrit (HCT), white blood cell count (WBC), and platelet count (PLT) in minipigs. Medians of HGB, RBC, HCT, WBC and PLT were significantly higher in EDTA tubes than in CTAD tubes due to the dilution effect of the anticoagulant. We found a minor significant increase in HCT after 25.5 h in blood stored at 20 degrees C, and at the same time a minor significant increase in WBC in EDTA tubes stored at 20 degrees C. We found a significant decrease in PLT in blood stored at 5 degrees C, especially in EDTA tubes. Minor variations were also observed in HGB and RBC. Our results indicate that PLT should only be measured in tubes placed at room temperature. If HCT or WBC analyses are to be performed on the day after blood sampling, the samples must be stored in a refrigerator until analysis. Our studies underline that time delay before analysis of haematological variables can cause increased variation, and should therefore be limited as far as possible in order to reduce the number of animals needed to make reliable conclusions.     

Evaluation on the combined effect of Sesamin and Schisandra extract on blood fluidity

Several studies have demonstrated a link between blood viscosity and various forms of liver dysfunction. Therefore, we investigated the effect of liver protective herbal materials, Sesamin combined with extract of Schisandra chinensis berry (Schisandra) for its potential to improve blood fluidity in humans. Ten human subjects were recruited to study the effect of sesamin combined with schisandra extract (SCH) for two weeks on blood viscosity. Blood fluidity was measured as the transit time for 100mul of heparinized whole blood to pass through a micro-channel array setup at baseline, 1 week and 2 weeks. For safety assessment, blood biochemistry, hematology and urine analysis were taken at baseline, 1 week and 2 weeks after SCH administration. No safety concern and adverse effects were observed during the 2-week continuous intake period. Intake of SCH reduced blood passage time by 9.0% and 9.7% at 1 and 2 weeks, respectively. In conclusion, this pilot clinical study indicates that the combined administration of sesamin with schisandra extract could improve blood fluidity after 1 week of oral intake and this effect was sustained up to 2 weeks.     

Biological Rhythms in the Physiology and Pharmacology of Blood Coagulation

This article reviews the current knowledge on time-dependent variations in the physiology of blood coagulation and in the anticoagulant effect of heparin and warfarin. Animal data indicated that the shortest blood clotting time and the highest levels of coagulation factors II, VII, and IX were recorded during the resting period of the animal. These circadian rhythms were not altered by modifications of the lighting regimens. In healthy volunteers, the prothrombin time was longer at the end of the afternoon than early in the morning; the acro-phases of activated partial thromboplastin time and thrombin time occurred in the evening or during the night. The acrophases of fibrinogen, factors II, VII, VIII, and a-1-antitrypsin were obtained in the morning. There is no agreement on the chronobiology of platelet aggregation, and differences can be found in the time of maximal aggregability. The chronopharmacological studies of heparin infused at a constant rate to patients with thromboembolic diseases suggested that maximal effectiveness occurred at 04:00, while it was minimal at 08:00. Animal data indicated that oral administration of warfarin at the end of the activity period of rats produced maximal inhibition of vitamin K-dependent factors. This was the time of day when warfarin interference with the vitamin K cycle of the liver was highest. Further studies are needed to determine the clinical significance of biological rhythms in the physiology and pharmacology of blood coagulation.     

Biological Rhythms in the Physiology and Pharmacology of Blood Coagulation

This article reviews the current knowledge on time-dependent variations in the physiology of blood coagulation and in the anticoagulant effect of heparin and warfarin. Animal data indicated that the shortest blood clotting time and the highest levels of coagulation factors 11, VII, and IX were recorded during the resting period of the animal. These circadian rhythms were not altered by modifications of the lighting regimens. In healthy volunteers, the prothrombin time was longer at the end of the afternoon than early in the morning; the acrophases of activated partial thromboplastin time and thrombin time occurred in the evening or during the night. The acrophases of fibrinogen, factors 11, VII, VIII, and α-1-antitrypsin were obtained in the morning. There is no agreement on the chronobiology of platelet aggregation, and differences can be found in the time of maximal aggregability. The chronopharmacological studies of heparin infused at a constant rate to patients with thromboembolic diseases suggested that maximal effectiveness occurred at 04:00, while it was minimal at 08:00. Animal data indicated that oral administration of warfarin at the end of the activity period of rats produced maximal inhibition of vitamin K-dependent factors. This was the time of day when warfarin interference with the vitamin K cycle of the liver was highest. Further studies are needed to determine the clinical significance of biological rhythms in the physiology and pharmacology of blood coagulation.