Simultaneous measurements of lactate and blood flow during hypoxia and recovery from hypoxia in a localized region in the brain of the anesthetized rabbit

A haematological survey of farmed fallow deer (Dama dama) and red deer (Cervus elaphus) was carried out. In the winter period the red blood cell (RBC) count was 9.0 x 10(12)/L in adult fallow-does, and 6.1 x 10(12)/L in fawns. The haemoglobin (Hb) level and mean corpuscular volume (MCV) were also significantly (P < 0.05) lower in fawns than in adult fallow deer. In blood samples taken from red deer in different physiological and nutritional periods, the stags showed the lowest mean RBC count in January (4.7 x 10(12/L) and the hinds during lactation (6.3 x 10(12)/L). The mean RBC count of samples taken from a group of red deer fawns at five different times between 1 week and 1 year of age varied between 5.8 and 7.0 x 10(12)/L. In red deer herds the RBC count showed minor variations and the Hb concentration was almost constant in the different periods. The coefficient of correlation between RBC and Hb was 0.66 and 0.58 in fallow deer and red deer, respectively. Studying the blastogenic transformation of lymphocytes by immunological tests, a higher rate of response to non-specific mitogens (Phaseolus vulgaris, PHA; concanavalin A, Con A) was found in farmed deer (> 30%) than in deer captured in the wild and kept under farm conditions for 10 or 13 months (< 20%).     

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.     

Renal hemodynamics in the rat before and during inhibition of angiotensin II

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.     

The systemic hemodynamics of waking and anesthetized male cats during noradrenaline infusion

Dynamics of arterial pressure and its hemodynamic components were shoen to dramatically differ in corscious and anesthetised animals. The data obtained suggest that corscious male cats, along with a baroreflex mechanism of resistance against involvement of the heart into the pressor response, have another mechanism acting in deficiency of baroreflex effects.     

O2 uptake kinetics after acetazolamide administration during moderate- and heavy-intensity exercise

Inhibition of carbonic anhydrase (CA) is associated with a lower plasma lactate concentration ([La-]pl) during fatiguing exercise. We hypothesized that a lower [La-]pl may be associated with faster O2 uptake (V(O2)) kinetics during constant-load exercise. Seven men performed cycle ergometer exercise during control (Con) and acute CA inhibition with acetazolamide (Acz, 10 mg/kg body wt iv). On 6 separate days, each subject performed 6-min step transitions in work rate from 0 to 100 W (below ventilatory threshold, VE(T). Gas exchange was measured breath by breath. Trials were interpolated at 1-s intervals and ensemble averaged to yield a single response. The mean response time (MRT, i.e., time to 63% of total exponential increase) for on- and off-transients was determined using a two- (VE(T)). Arterialized venous blood was sampled from a dorsal hand vein and analyzed for [La-]pl. MRT was similar during Con (31.2 +/- 2.6 and 32.7 +/- 1.2 s for on and off, respectively) and Acz (30.9 +/- 3.0 and 31.4 +/- 1.5 s for on and off, respectively) for work rates VE(T), MRT was similar between Con (69.1 +/- 6.1 and 50.4 +/- 3.5 s for on and off, respectively) and Acz (69.7 +/- 5.9 and 53.8 +/- 3.8 s for on and off, respectively). On- and off-MRTs were slower for >VE(T) than for VE(T) exercise but was lower at the end of the transition during Acz (1.4 +/- 0.2 and 7.1 +/- 0.5 mmol/l for VE(T) respectively) than during Con (2.0 +/- 0.2 and 9.8 +/- 0.9 mmol/l for VE(T), respectively). CA inhibition does not affect O2 utilization at the onset of VE(T) exercise, suggesting that the contribution of oxidative phosphorylation to the energy demand is not affected by acute CA inhibition with Acz.     

O2 extraction maintains O2 uptake during submaximal exercise with beta-adrenergic blockade at 4,300 m

Whole body O2 uptake (VO2) during maximal and submaximal exercise has been shown to be preserved in the setting of beta-adrenergic blockade at high altitude, despite marked reductions in heart rate during exercise. An increase in stroke volume at high altitude has been suggested as the mechanism that preserves systemic O2 delivery (blood flow x arterial O2 content) and thereby maintains VO2 at sea-level values. To test this hypothesis, we studied the effects of nonselective beta-adrenergic blockade on submaximal exercise performance in 11 normal men (26 +/- 1 yr) at sea level and on arrival and after 21 days at 4,300 m. Six subjects received propranolol (240 mg/day), and five subjects received placebo. At sea level, during submaximal exercise, cardiac output and O2 delivery were significantly lower in propranolol- than in placebo-treated subjects. Increases in stroke volume and O2 extraction were responsible for the maintenance of VO2. At 4,300 m, beta-adrenergic blockade had no significant effect on VO2, ventilation, alveolar PO2, and arterial blood gases during submaximal exercise. Despite increases in stroke volume, cardiac output and thereby O2 delivery were still reduced in propranolol-treated subjects compared with subjects treated with placebo. Further reductions in already low levels of mixed venous O2 saturation were responsible for the maintenance of VO2 on arrival and after 21 days at 4,300 m in propranolol-treated subjects. Despite similar workloads and VO2, propranolol-treated subjects exercised at greater perceived intensity than subjects given placebo at 4,300 m. The values for mixed venous O2 saturation during submaximal exercise in propranolol-treated subjects at 4,300 m approached those reported at simulated altitudes >8,000 m. Thus beta-adrenergic blockade at 4,300 m results in significant reduction in O2 delivery during submaximal exercise due to incomplete compensation by stroke volume for the reduction in exercise heart rate. Total body VO2 is maintained at a constant level by an interaction between mixed venous O2 saturation, the arterial O2-carrying capacity, and hemodynamics during exercise with acute and chronic hypoxia.     

Renal extraction of gentamicin in anesthetized dogs

Follow-up examinations, ranging from four to more than 20 years, were performed on 100 patients with chronic cyclitis whose ages at onset were from 4 to 58 years. Cataracts were found in 42% of eyes and macular disease secondary to macular edema in 28% of eyes. Band keratopathy, glaucoma, retinal detachment, retinoschisis, vitreous hemorrhage, retinal hemorrhage, and vessels leaving the disk margin were also noted. The complications resulting in decreased vision in chronic cyclitis were macular edema in active cases and macular degenerative changes in the late inactive stages. Of all eyes with final visual acuity of 6/12 (20/40) or less, 74% had permanent, late macular changes secondary to earlier cystoid macular edema. Vitreous opacities or cells, or both, caused decreased visual acuity in the early active stages of chronic cyclitis but were not major factors in the ultimate visual prognosis in the late inactive stages. At the final examination, vitreous opacities caused a visual loss in only 9% of the eyes that had visual acuity of 6/12 (20/40) or less. It was difficult to determine whether corticosteroids caused cataract formation and glaucoma.     

Nitric oxide-mediated renal epithelial cell injury during hypoxia and reoxygenation

If two targets are both on the visual axis of one eye or the other, and binocular fixation is shifted from the farther one to the nearer, the aligned eye consistently makes an initial, seemingly pointless saccade in a temporal direction. The size of those saccades typically differs markedly, depending on whether the targets are aligned with the observer's dominant or non-dominant eye. Pickwell [(1972) Vision Research, 12, 1499-1507] proposed that this binocular asymmetry in oculomotor performance reflects a subject-specific lateral displacement of the egocenter (the "binoculus" of Hering, which has traditionally been assumed to be on the midline). An empirical test of Pickwell's widely endorsed hypothesis has now been conducted and the proposal has been found wanting. In an otherwise darkened room, subjects were required repeatedly to set a small light to a perceived straight-ahead location in the horizontal plane, first for a target at 300 cm distance and then for one at 30 cm. Extrapolation of a line that connects the two averages of those settings to the inter-ocular axis provides an estimate of the subjective egocenter to which visual directions are referred. Contrary to Pickwell's proposal, those locations of the inferred egocenter were usually quite near the midline, and were completely uncorrelated with same-subject data on the extent of saccadic asymmetry at the onset of asymmetrical convergence. The data on perceived straight-ahead underlying this result indicate the availability of extraretinal information about eye orientation that is quite precise at a given moment (median standard deviation of 47 min arc) but conspicuously non-stationary over several-minute intervals (monotonic drifts in sequential settings being very common).     

Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs

Smyth line (SL) chickens develop a spontaneous, autoimmune, posthatch loss of pigment cells (vitiligo) in regenerating feather tissue. Smyth line vitiligo (SLV) is associated with lymphocyte infiltrations prior to and throughout the development of the disorder. It was the purpose of this study to determine the type, relative amounts, and proportions of pulp-infiltrating lymphocytes at various times throughout the growth of regenerating feathers. Feathers were plucked from 8-week-old chickens with and without SLV. Feather pulp cell suspensions were prepared when the regenerating feathers were 2, 3, 4, and 6 weeks of age. Cells were fluorescently labeled using a panel of mouse monoclonal antibodies specific for chicken lymphocytes. Both T and B cells infiltrated the feather pulp of chickens with SLV. T cell levels remained elevated throughout the 6 weeks of feather growth, while B cell levels steadily declined to control levels over the same time. The pulp-infiltrating cells were primarily T cells with an alphabeta T cell receptor expressing the Vbeta1 gene (TCR2+). The ratio between CD4+ and CD8+ cells was 1.42 and 0.75 in 2- and 6-week-old regenerating feathers from chickens with autoimmune SLV, respectively. In non-vitiliginous chickens this ratio was always near 1. These data suggest that TCR2+ T cells play an important role in SLV. CD4+ cells may play a recruiting/activating role, whereas CD8+ cells may have cytotoxic activity specifically directed against melanocytes. Additionally, this is the first report demonstrating the infiltration of B cells into the feather pulp of vitiliginous chickens. These B cells may directly/indirectly contribute to melanocyte destruction in SLV.     

Comparison of ozone-induced effects on lung mechanics and hemodynamics in the rabbit

The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in Po (approximately 51%) compared with caffeine-induced force (approximately 11-21%), we estimate that E-C coupling failure can explain 57-75% of the Po decrement from 0 to 5 days postinjury. Comparable reductions in Po and K+-induced force (51%), and minor reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol-induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease in Po during the first several days after injury primarily stems from a failure in the E-C coupling process.     

Current concepts of renal hemodynamics in diabetes

Glomerular hyperfiltration has long been recognized in insulin-dependent diabetes, and has been more recently recognized in patients with non-insulin dependent diabetes mellitus as well. Experimentally, glomerular hyperfiltration has been shown to result from elevations in the glomerular capillary blood flow and the glomerular capillary hydraulic pressure (PGC). Of the hemodynamic determinants of hyperfiltration, it is glomerular hypertension that is most damaging to the glomerulus. Experimental and clinical studies have confirmed that antihypertensive agents that lower PGC more consistently slow the progression of injury than do those that fail to control glomerular hypertension. The pathogenesis of diabetic hyperfiltration is multifactoral. Many mediators have been proposed, including changes due to the altered metabolic milieu, and alterations in endogenous levels of such vasoactive mediators as atrial natriuretic peptide, endothelial-derived relaxing factor, angiotensin II, prostaglandins, thromboxanes, and kinins, among others. It has more recently been suggested that local renal tissue levels, rather than circulating levels, play the more profound role in hemodynamic regulation. For example, the renin-angiotensin system (RAS) appears to be disproportionately active in the renal tissue, potentially explaining the renal vascular responsiveness to angiotensin-converting enzyme inhibition despite absence of systemic RAS activation. Little is yet known of the mechanisms by which glomerular hypertension leads to injury. Innovative new in vitro systems have been developed to address this question. These studies postulate that glomerular hemodynamic factors (shear stress, pulsatile flow) modify the growth and activity of glomerular component cells, inducing the expression of cytokines and other mediators, which then stimulate matrix production and promote structural injury.     

Effect of N-methyl-D-aspartate receptor blockade on the control of cerebral O2 supply/consumption balance during hypoxia in newborn pigs

Using dizocilpine (MK-801), we tested the hypothesis that N-methyl-D-aspartate (NMDA) receptors are important controllers of cerebral O2 supply/consumption balance in newborn piglets both during normoxia and hypoxia. Twenty-five 2 to 7-day-old piglets were anesthetized and divided into four groups: (1) Normoxia (n = 6), (2) Normoxia + MK-801 (n = 6), (3) Hypoxia (n = 6), and (4) Hypoxia + MK-801 (n = 7). Regional cerebral blood flow (rCBF) in ml/min/100 g was measured using 14C-iodoantipyrine, and we determined arterial and venous O2 saturations by microspectrophotometry, calculating cerebral O2 consumption (VO2) in ml O2/min/100 g in the cortex, hypothalamus and pons. MK-801 did not significantly affect regional VO2 or rCBF in normoxic piglets. Hypoxia resulted in an increase in local rCBF compared to controls: from 41 +/- 6 to 103 +/- 18 in the cortex; 34 +/- 7 to 101 +/- 20 in the hypothalamus; and 45 +/- 10 to 95 +/- 11 in the pons. Pretreatment with MK-801 abolished this hypoxic flow effect in the cortex (51 +/- 2) and hypothalamus (49 +/- 5), but not in the pons (91 +/- 17). Similar results were observed for VO2 with control values of 1.9 +/- 0.3, 1.6 +/- 0.2 and 2.1 +/- 0.3 for the cortex, hypothalamus and pons respectively. Hypoxia resulted in an increase in the VO2 to 3.9 +/- 0.4 (cortex), 3.8 +/- 0.6 (hypothalamus) and 3.9 +/- 0.8 (pons). Pretreatment with MK-801 prior to hypoxia abolished these effects in the cortex (2.1 +/- 0.2) and hypothalamus (2.1 +/- 0.2), but not in the pons (2.9 +/- 0.2). These findings suggest that NMDA receptors may play a role in the control of cerebral metabolism during hypoxia in this immature porcine model.     

Effect of neuropeptide Y on hemodynamics of the rabbit lung

We evaluated the effect of neuropeptide Y (NPY) on the hemodynamics of the isolated rabbit lung perfused at constant flow and outflow pressure. Doses of 10(-8) and 10(-7) M NPY increased pulmonary arterial pressure (Ppa) from 11.5 +/- 1.0 (SE) mmHg to, respectively, 16.4 +/- 1.5 and 26.0 +/- 3.8 mmHg (P < 0.05, n = 5 mmHg lungs), with 78 +/- 4% of the increase at 10(-7) M resulting from an increased arterial resistance. At the latter dose, pulmonary capillary pressure increased from 5.8 +/- 0.9 to 9.4 +/- 1.0 mmHg (P < 0.05). When administered in the presence of norepinephrine, 10(-8) and 10(-7) M NPY (n = 6) produced extreme increases in Ppa to 66.1 +/- 20.5 and 114.7 +/- 25.5 mmHg, respectively, that were due primarily to an increased arterial resistance. To determine the significance of circulating NPY as a pulmonary vasoactive agent, we measured plasma NPY-like immunoreactivity in anesthetized rabbits after massively activating the sympathetic nervous system with veratrine. NPY-like immunoreactivity increased from 74 +/- 10 to 111 +/- 10 (SE) pM (P < 0.05). Thus, although NPY is a potent vasoconstrictor in the rabbit lung, it is not likely that plasma NPY concentrations rise sufficiently, even after massive sympathetic nervous system activation, to produce pulmonary vasoconstriction in the intact rabbit.     

Influence of the renal endothelin A system on the autoregulation of renal hemodynamics in SHRs and WKY rats

In this study, we investigated the influence of a short-term blockade of the renal endothelin A system on the autoregulation of total renal blood flow, cortical renal blood flow, and pressure-dependent plasma renin activity in spontaneously hypertensive rats (SHRs) and normotensive controls [Wistar-Kyoto (WKY) rats]. In anesthetized rats, renal blood flow was measured by a transit-time flow probe and cortical blood flow by a laser flow probe. Blood samples were taken for measurement of plasma renin activity. Renal perfusion pressure was reduced in 5-mm Hg steps by means of a servocontrolled electropneumatic device by an inflatable suprarenal cuff. During the experiments, the rats (n = 6, each group) received an intrarenal infusion of either the selective endothelin A-receptor antagonist BQ123 (3 mg/kg/h) or vehicle. We observed an improvement of total and cortical blood flow autoregulation as indicated by a shift of lower limits of autoregulation to lower threshold pressures [103 +/- 2 vs. 132 +/- 4 mm Hg compared with 98 +/- 3 vs. 120 +/- 4 mm Hg (mean +/- SEM); p < 0.01 resp. p < 0.05] in BQ123-treated SHRs, whereas BQ123 had no influence on breakpoints of autoregulation in WKY rats (p > 0.05). Pressure-dependent plasma renin activity in SHRs was not influenced by BQ123. Renal blood flow autoregulation is improved in SHRs after short-term blockade of the renal endothelin A system. This effect is independent of the renin-angiotensin system. The endothelin A system does not seem to play an important role in the autoregulation of renal blood flow in normotensive WKY rats.     

Sarcoplasmic reticulum Ca2+ uptake and thapsigargin sensitivity in permeabilized rabbit and rat ventricular myocytes

Ca2+ uptake by the sarcoplasmic reticulum (SR) and free [Ca2+] were measured simultaneously with indo 1 and a Ca(2+)-selective minielectrode in suspensions of permeabilized rabbit or rat ventricular myocytes (approximately 10 mg/mL protein). In the presence of 25 mumol/L ruthenium red and 10 mmol/L oxalate, the Km for Ca2+ uptake by the SR was approximately 250 nmol/L in rabbit and rat ventricular myocytes. The maximal Ca2+ uptake rate was 2.4 times higher in rat than in rabbit. Addition of 5 nmol thapsigargin (TG) per milligram cell protein abolished Ca2+ uptake completely in both species. The [TG] necessary for a half-maximal reduction of the uptake rate (K1/2) was 55 pmol/mg cell protein for rabbit and 390 pmol/mg cell protein for rat. Assuming that the number of pump sites is two times the concentration of TG necessary to inhibit half of the Ca2+ pump activity (ie, the TG affinity is very high), the density of pump sites is 7.7 mumol/kg wet wt for rabbit and 54.6 mumol/kg wet wt for rat. Despite a fivefold decrease of the Ca2+ uptake rate by a submaximal [TG], the permeabilized myocytes were still able to lower the free [Ca2+] to < 150 nmol/L from a peak value > 10 mumol/L. The relative inhibition of Ca2+ uptake by TG did not depend on the free [Ca2+]. Addition of more than 5 nmol TG per milligram cell protein abolished Ca2+ uptake by the SR completely in < 15 seconds and reduced the uptake rate by 95% in 5 seconds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase transformations during the interaction of Nb2O5 and FeNb2O6 with aluminum

The phase transformations that occur during the interaction of niobium pentoxide and iron niobate with aluminum are studied by differential scanning calorimetry, X-ray diffraction analysis and electronprobe microanalysis. The sequence of the formation of intermediate phases based on an NbO₂ solid solution is revealed. It is shown that the reduction of niobium from Nb₂O₅ is hindered by the formation of hard-to-reduce oxides Al₂O₃ · 25Nb₂O₅, Al₂O₃ · 9Nb₂O₅ and AlNbO₄. The interaction of FeNb₂O₆ with aluminum is accompanied by the formation of [(Fe,Nb)O₂]_s.s and NbO₂ solid solutions.     

Solidus surface and phase equilibria during the solidification of alloys in the Al2O3-ZrO2-Y2O3 system

The projection of the solidus surface in the Al₂O₃-ZrO₂-Y₂O₃ phase equilibrium diagram was plotted. The scheme of alloy solidification indicates that the primarily congruent modes of phase transformation in the limiting binary systems are retained in the ternary system.Institute of Materials Science Problems, Ukrainian Academy of Sciences. Kiev. Translated from Poroshkovaya Metallurgiya, Nos. 1/2(377), pp. 71–76, January–February, 1975.