Oxygen supply of the brain cortex in acute nitrite hypoxia in rodents with different ecological specialization

Microhemodynamics and oxygen tension (pO₂) in the brain cortex tissues as well as the heart rate were studied in rodents with different ecological specialization during hypoxia produced by subcutaneous injection of sodium nitrite (3 mg/100 g body mass). It was shown that the blood flow in animals with low (rats) and high (muskrats) resistance to hypoxia decreased by the 30th min of the nitrite action, with its subsequent restoration to 85% and 83% of the initial level by the 60th min. The interspecies difference consisted in an increase of the brain blood flow (by 24%) in muskrats and a decrease (by 33%) in rats 15 min after the injection. In rats, simultaneously with the blood-flow dynamics, a pO₂ increase was observed in some brain cortex microareas, while in others—a pO₂ decrease 15 min after the NaNO₂ injection: meanwhile, in muskrats, at this time period a significant pO₂ decrease was observed on the background of a blood flow increase. In both animal species, the pO₂ minimal value was reached by the 45th min, while restoration almost to the initial levels—by the 60th min of the nitrite action. Changes in the rats, synchronous and unidirectional with the heart rate frequency, of the brain blood-flow, as well as tachycardia developing throughout the whole experiment in rats allow suggesting that restoration of the oxygen regime in the brain cortex microareas is provided by activation of systemic mechanisms of regulation of circulation.     

Effects of stimulating surface during static upright posture in the elderly

Abstract

This study aimed to investigate the influence of three stimulating surfaces based on center of pressure (CoP), anteroposterior sway velocity (V_A/P), and medio-lateral sway velocity (V_M/L) of 40 elderly subjects. CoP and V_M/L showed a significant decrease in all visual conditions only in the stimulating surface whereas V_A/P showed a significant decrease only on the same surface with eyes open. Results confirm the importance of multisensory stimulation in postural control in the elderly.     

Renal compensation for cecal loss in Gambel's quail (Callipepla gambelii)

Some studies have implicated the avian digestive cecae as important sites of water and solute reclamation working in concert with the lower intestine and the kidneys as part of an integrated osmoregulatory system. In Gambel's quail (Callipepla gambelii), we studied compensatory adjustments in renal function on days 6–7 and 16–17 following ligation of cecae. Plasma osmolality (P_osm) varied significantly between groups with sham-operatd birds (Cs), with an average (P_osm) of 348 mOsm/kg H₂O and quail with ligated cecae (Cx) having a (P_osm) of 355 mOsm/kg H₂O. We detected no change in the rate of glomerular filtration (GFR) between experimental and control groups either shortly after cecectomy or after 16–17 d following surgery. Regression analysis of GFR and urine flow rate (V) showed that Cx birds had a significantly lower V at a given GFR than did controls, evidence that Cx quail absorbed more fluid in their renal tubules. Increased fluid reabsorption was apparently driven by an enhanced reabsorption of sodium. Indeed, sodium excretion was lower in Cx quail as compared to sham-operated birds. On days 6–7, Cx quail drank more water than Cs birds, but by days 16–17 drinking rates were similar. At the end of the experiments, Cx quail showed a proliferation of microvilli along the apical membrane of the rectum, an adjustment consistent with the idea that the rectum alters its absorption capacity to adjust for the loss of cecal function.     

Analysis of a conjugate between anti-carcinoembryonic antigen monoclonal antibody and alkaline phosphatase for specific activation of the prodrug etoposide phosphate

Summary The selective targeting of tumours by enzymes conjugated to monoclonal antibodies (mAb) may be an ideal approach to convert relatively nontoxic prodrugs into active agents at the tumour site. We used the anti-carcinoembryonic antigen mAb BW431/26 conjugated to alkaline phosphatase (AP) and phosphorylated etoposide (etoposide-P) as a prodrug to study the feasibility of this concept. Etoposide was phosphorylated with POCl₃. Quantitative hydrolysis of etoposide-P to etoposide occurred within 10 min in the presence of AP. BW431/26 and AP were conjugated using a thioether bond. The AP conjugate retained 93% of its calculated activity.¹²⁵I-labelled AP conjugate did not show a reduction of immunoreactivity as determined by a cell-binding assay. SW1398 colon cancer cells were used to analyse the cytotoxicity of etoposide and etoposide-P. Etoposide (IC₅₀ 22 µM) was 100 times more toxic than etoposide-P (20% growth inhibition at 200 µM). Pretreatment of the cells with BW431/26-AP prior to etoposide-P exposure resulted in a dramatic increase in cytotoxicity (IC₅₀ 70 µM). The pharmacokinetics and tumour-localizing properties of BW431/27 and the AP conjugate were assessed in nude mice bearing SW1398 tumours. BW431/26 showed excellent tumour localization (10% of the injected dose/g tissue retained from 8 h to 120 h), whereas the AP conjugate showed a reduced tumour uptake (3%-0.3% of the injected dose/g tissue at 8–120 h), a faster clearance from the circulation and a high liver uptake. Radiolabelled AP showed a similar pharmacokinetic profile to the AP conjugate. Gel filtration analysis of blood, liver, and tumour samples indicated good stability of the conjugate.     

3HOH-osmotic water fluxes and ultrastructure of an epithelial syncytium

Summary Ultrastructural changes associated with osmotically-induced water transport and water permeability were examined in two flatworm species,Schistosoma mansoni andHymenolepis diminuta. The structure of the surface layer of these parasites is unusual in that it is a syncytial epithelial layer that lacks tight junctions and lateral extracellular spaces. The permeability coefficients observed in this study are therefore necessarily associated only with the transcellular route of transepithelial transport. The ultrastructural changes associated with volume transport across the epithelial syncytium were also unusual in that the basally located channels extending distally from the inward-facing membrane into the syncytial layer remained open regardless of the direction of water flow.Despite the structural differences, most of the features of diffusive (P _d ) and osmotic (P _osm ) water fluxes across the syncytium resembled those observed in other epithelia: (i) Low water permeability with maximum values of 4.1×10^–5 forP _d and 9.6×10^–5 forP _osm.(ii)P _osm>P _d by 2.0- to 3.2-fold. (iii) Outward water permeability less than inward water permeability. This asymmetry could not be attributed to collapsing channels when net volume transport was directed outward since channels in the syncytium remained open regardless of the direction of water flow. The asymmetry could be explained by tissue contraction or swelling when bathed in anisotonic fluids. (iv)P _osm values were not significantly altered by tissue unstirred layers but bothP _osm andP _d values were underestimated when the bulk fluid was not vigorously stirred.The lower permeability inS. mansoni relative toH. diminuta may be attributed to the membranous surface coat of the former species.     

Effects of hydration state on hormonal and renal responses during moderate exercise in the heat

The effects of hydromineral hormones and catecholamines on renal concentrating ability at different hydration states were examined in five male volunteers while they performed three trials. Each of these trials comprised a 60-min exercise bout on a treadmill (at 50% of maximal oxygen uptake) in a warm environment (dry bulb temperature, 35°C; relative humidity, 20–30%). In one session, subjects were euhydrated before exercise (C). In the two other sessions, after thermal dehydration (loss of 3% body mass) which markedly reduced plasma volume (PV) and increased plasma osmolality (osm_pl), the subjects exercised either not rehydrated (Dh) or rehydrated (Rh) by drinking 600 ml of mineral water before and 40 min after the onset of exercise. During exercise in the Dh compared to C state, plasma renin, aldosterone, arginine vasopressin (AVP), noradrenaline and adrenaline concentrations were increased (P < 0.05). A reduction in creatinine clearance and urine flow was also observed (P < 0.05) together with a decrease in urine osmolality, osmolar clearance and sodium excretion, while free water clearance increased (P < 0.05). However, compared to Dh, Rh partially restored PV and osm_pl and induced a marked reduction in the time courses of both the plasma AVP and catecholamine responses (P < 0.05). Values for renal water and electrolyte excretion were intermediate between those of Dh and C. Plasma atrial natriuretic peptide presented similar changes whatever the hydration state. These results demonstrate that during moderate exercise in the heat, renal concentrating ability is paradoxically reduced by prior dehydration in spite of high plasma AVP levels, and might be the result of marked activation of the sympatho-adrenal system. Rehydration, by reducing this activation, could partially restore the renal concentrating ability despite the lowered plasma AVP. Accepted: 23 April 1997     

Effects of indomethacin on cardiac output distribution in normal and asphyxiated piglets

We determined the effect of breathing 9% CO₂/10% O₂/81% N₂ (asphyxia) on cardiac output distribution (microspheres) in 4–5 day old unanesthetized, chronically instrumented piglets prior to and following intravenous indomethacin administration. Thirty minutes of asphyxia caused Pa_CO2 to increase from 35 ± 2 mmHg to 66 ± 2 mmHg, Pa_O2 to decrease form 73 ± 4 mmHg to 41 ± 1 mmHg, and pH to decrease from 7.52 ± 0.05 to 7.21 ± 0.07. Arterial pressure was increased slightly but cardiac output was not changed significantly. Asphyxia caused blood flow to the brain, diaphragm, liver, heart, and adrenal glands to increase while causing decreases in blood flow to the skin, small intestine, and colon. Blood flows to the stomach and kidneys tended to decrease, but the changes were not significant. Treatment with indomethacin during asphyxia did not alter arterial pressure or cardiac output but decreased cerebral blood flow to the preasphyxiated level and decreased adrenal blood flow about 20%. Indomethacin did not alter blood flow to any other systemic organ. At this time the piglet was allowed to breathe air for 2.5 hr undisturbed. Two and a half hours after indomethacin administration, blood flows to all organs returned to the preasphyxia control levels with the exception of cerebral blood flow which was reduced (93 ± 13 to 65 ± 5 ml/100 g·min. Three hours after indomethacin administration, the cerebral hyperemia caused by asphyxia was less (134 ± 17b ml/100 g·min) than prior to indomethacin (221 ± 15 ml/100 g·min. Indomethacin did not alter the asphyxia-induced changes to any other systemic organ. We conclude that in newborn pigs, systemic treatment with indomethacin decreases cerebral blood flow and cerebral hyperemia in response to asphyxia, without affecting blood flow to any other systemic organ.     

Effects of interval training at the ventilatory threshold on clinical and cardiorespiratory responses in elderly humans

This study assessed clinical and cardiorespiratory responses after an interval training programme in sedentary elderly adults using the ventilatory threshold (V _th) as the index of exercise training intensity. A selection of 22 subjects were randomized into two groups: 11 subjects served as the training group (TG) and the others as controls (CG). Maximal exercise tests were performed on a treadmill before (T₀), each month (T₁, T₂) and after the 3-month interval training programme period (T₃). The TG subjects were individually trained at the heart rate corresponding to V _th measured at T₀, T₁ and T₂ as the breakpoint in the oxygen uptake-carbon dioxide production relationship. Their training programme consisted of walking/jogging sessions on a running track twice a week. The sessions consisted of varying durations of exercise alternating with active recovery in such a way that the subjects slowly increased their total exercise time from an initial duration of 30 min to a final duration of 1 h. During training the heart rate was continuously monitored by a cardiofrequency meter. Compared with the daily activities of the controls, no training programme-related injuries were observed in TG. Moreover, programme adherence (73%) and attendance (97.3%) were high. The maximal oxygen uptake and V _th were increased in TG, by 20% (P<0.05) and 26% (P<0.01), respectively. Interval training at V _th also significantly increased maximal O₂ pulse (P<0.05) and maximal ventilation (P<0.01). A significant decrease in submaximal ventilation (P<0.05) and heart rate (P<0.01) was also noted. These results would suggest that for untrained elderly adults, an interval training programme at the intensity of V _th may be well-tolerated clinically and may significantly improve both maximal aerobic power and submaximal exercise tolerance. Accepted: 6 January 1998     

Oxygen regime in rat brain tissues under conditions of acute nitrite methemoglobinemia

Oxygen regime in rat brain tissues was studied under conditions of nitrite hypoxia. The local brain circulation (LCC) and pO₂ were recorded by polargraphic method in microareas of the brain cortex one hour after a subcutaneous injection of NaNO₂ (3 mg/100 g body mass). A LCC decrease by 55% was shown by the 30th min of the nitrite intoxication, with its restoration to 85% of the initial blood-flow by the 60th min. In some brain microareas, a pO₂ increase by 40.7% was observed by the 45th min of the action and its decrease by 32.2% by the 60th min, whereas in other microareas, a pO₂ decrease by 24.5% with its subsequent increase to 78.7% of the initial level, respectively. A statistically significant correlation is revealed between changes of the oxygen pressure in the process of development of nitrite hypoxia and the LCC dynamics. It is concluded that the circulatory disturbances developing at the first moments of the nitrite action lead to an increase of the degree of the pO₂ differentiated distribution in the brain: to hyperoxygenation in some microareas and to severe hypoxia in others, what can be the cause of functional brain disturbances under the effect of nitrogen oxides.     

Circulatory function at sub-zero temperature: venous responses to catecholamines and angiotensin II in the Antarctic fish <Emphasis Type="Italic">Pagothenia borchgrevinki</Emphasis>

Catecholamines increase arterial pressure by increasing cardiac output (Q) and stroke volume (V _s), while angiotensin II (ang II) also increases vascular resistance (R _sys) in the Antarctic fish Pagothenia borchgrevinki. Adrenaline, phenylephrine and ang II (Asn¹, Val⁵) were injected into P. borchgrevinki. Cardiovascular variables, including central venous pressure (P _cv) and mean circulatory filling pressure (P _mcf; an index of venous capacitance), were recorded to investigate if venous vasoconstriction can explain the increased V _s and Q and the arterial pressor response in this species. Routine P _cv and P _mcf were 0.11 ± 0.01 and 0.18 ± 0.02 kPa, respectively. All of the drugs caused moderate increases in P _cv and P _mcf and the responses were attenuated after α-adrenergic blockade with prazosin. Although dorsal aortic pressure (P _da) also increased in response to all agonists, the mechanisms differed. Adrenaline caused sustained increases in V _s and Q, while R _sys only rose transiently. Ang II had a slower effect than adrenaline and increased both R _sys and Q, while phenylephrine only increased R _sys. This study demonstrates that P _cv is positive and controlled by an α-adrenergic mechanism in P. borchgrevinki. However, given the relatively small venous response to adrenaline it seems more likely that the increases in V _s and Q from this agonist are due to direct effects on the heart.     

Pre-and post-branchial blood respiratory status during acute hypercapnia or hypoxia in rainbow trout,Oncorhynchus mykiss

Simultaneous venous (pre-branchial) and arterial (post-branchial) extracorporeal blood circulations were utilized to monitor continuously the rapid and progressive effects of acute environmental hypercapnia (water partial pressure of CO₂ 4.8±0.2 torr) or hypoxia (water partial pressure of O₂ 25±2 torr) on oxygen and carbon dioxide tensions and pH in the blood of rainbow trout (Oncorhynchus mykiss). During hypercapnia, the CO₂ tension in the arterial blood increased from 1.7±0.1 to 6.2±0.2 torr within 20 min and this was associated with a decrease of arterial extracellular pH from 7.95±0.03 to 7.38±0.03; the acid-base status of the mixed venous blood changed in a similar fashion. The decrease in blood pH in vivo was greater than in blood equilibrated in vitro with a similar CO₂ tension indicating a significant metabolic component to the acidosis in vivo. Under normocapnic conditions, venous blood CO₂ tension was slightly higher than arterial blood CO₂ tension difference was abolished or reversed during the initial 25 min of hypercapnia indicating that CO₂ was absorbed from the water during this period. Arterial O₂ tension remained constant during hypercapnia; however, venous blood O₂ tension decreased significantly (from 22.0±2.6 to 9.0±1.0 torr) during the initial 10 min. Hypercapnia elicited the release of catecholamines (adrenaline and noradrenaline) into the blood. The adrenaline concentration increased from 6±3 to 418±141 nmol · l^-1 within 25 min; noradrenaline concentration increased from 3±0.5 to 50±21 nmol · l^-1 within 15 min. During hypoxia arterial blood O₂ tension declined progressively from 108.4±9.9 to 12.8±1.7 torr within 30 min. Venous blood O₂ tension initially was stable but then decreased abruptly as catecholamines were released into the circulation. The release of catecholamines occurred concomitantly with a sudden metabolic acidosis in both blood compartments and a rise in CO₂ tension in the mixed venous blood only.Abbreviations CCO₂ plasmatotal carbondioxide - CtO₂ blood oxygen content - PO₂ partial pressure of oxygen - PCO₂ partial pressure of carbon dioxide - PaO₂ arterial bloodPO₂ - PaCO₂ arterial bloodPCO₂ - PvCO₂ venous bloodPCO₂ - PwO₂ waterPO₂ - PwCO₂ waterPCO₂ - Hb haemoglobin - SHbO₂ haemoglobin oxygen saturation - HPLC high-performance liquid chromatography - rbc red blood cell(s) - Hct haematocrit     

Relationship between oxygen saturation of mixed venous blood and pressure in the pulmonary artery trunk in healthy humans and patients with heart defects

The relationship between pulmonary artery pressure (P _LA) and oxygen saturation of mixed venous blood (S _V ) has been studied in subjects (1750 men and 1026 women) subdivided into 12 groups. Functional relationships have been found between P _LA and S _V , P _LA = f(S _V ), and S _V = f(P _LA), which were estimated using direct measurement of P _LA and S _V for each group. These factors have been found to obey the following dependences: P _LA = f(S _V ) and P _LA = a(S _V )^−b , where b = −0.2284a + 0.6564 in men and b = −0.285a + 1.2947 in women; S _V = f(P _LA) and S _V = c(P _LA)^−d , where d = −0.25131Ln(c) + 1.0212; R ² = 0.8993 in men and d = −1.9645Ln(c) + 2.852; and R ² = 0.9674 in women. Each group occupies a position on the curves specified by the equations. Subjects with the diagnosis of a functional heart murmur and patients with congenital aortic valve stenosis were grouped together to form the so-called normal group characterized by specific P _LA = f(S _V ) and S _V = f(P _LA) dependences. Male patients with coronary heart disease were also included in the normal group. An equation was derived to relate P _LA caused by different reasons with the corresponding saturation of mixed venous blood. In the case of the changing saturation of mixed venous blood, this equation gives the corresponding value of P _LA. Equilibrium between systemic and pulmonary circulations is established through interdependent changes in the physiological indices of blood circulation and gas exchange in humans.     

Osmotin induces cold protection in olive trees by affecting programmed cell death and cytoskeleton organization

Osmotin is a pathogenesis-related protein exhibiting cryoprotective functions. Our aim was to understand whether it is involved in the cold acclimation of the olive tree (Olea europaea L.), a frost-sensitive species lacking dormancy. We exposed olive trees expressing tobacco osmotin gene under the 35S promoter (35S:osm) [in the same manner as wild type (wt) plants] to cold shocks in the presence/absence of cold acclimation, and monitored changes in programmed cell death (PCD), cytoskeleton, and calcium ([Ca²⁺]_c) signalling. In the wt, osmotin was immunolocalized only in cold-acclimated plants, and in the tissues showing PCD. In the 35S:osm clones, the protein was detected also in the non-acclimated plants, and always in the tissues exhibiting PCD. In the non-acclimated wt protoplasts exposed to cold shock, a transient decrease in phallotoxin signal suggests a temporary disassembly of F-actin, a transient increase occurred instead in 35S:osm protoplasts exposed to the same shock. Transient increases in [Ca²⁺]_c were observed only in the wt protoplasts. However, when F-actin was depolymerized by cytochalasin or latrunculin, and microtubules by colchicine, increase in [Ca²⁺]_c also occurred in the 35S:osm protoplasts. Successive cold shocks caused transient rises in [Ca²⁺]_c and transient decreases in the phallotoxin signal in wt protoplasts. No change occurred in [Ca²⁺]_c occurred in the 35S:osm protoplasts. The phallotoxin signal transiently increased at the first shock, but did not change after the subsequent shocks, and an overall signal reduction occurred with shock repetition. Following acclimation, no cold shock-induced change in [Ca²⁺]_c levels and F-actin signal occurred either in wt or 35S:osm protoplasts. The results show that osmotin is positively involved in the acclimation-related PCD, in blocking the cold-induced calcium signalling, and in affecting cytoskeleton in response to cold stimuli.     

Photoinhibition of photosynthesis in willow leaves under field conditions

Chlorophyll fluorescence of leaves of a willow (Salix sp.) stand grown in the field in northern Sweden was measured on several occasions during the growing season of 1987. For leaves that received mostly full daylight, the F _V/F _P ratio declined roughtly 15% in the afternoon on cloudless days in July (F _P is the fluorescence at the peak of the induction curve obtained at the prevailing air temperature after 45 min of dark adaptation, and F _V is variable fluoresence, F _V=F _P-F _O, where F _O is minimal fluorescence). There was no decrease in the F _V/F _P ratio on cloudy days, while the effect was intermediate on changeable days. In view of this light dependence, together with the fact that the decline in the F _V/F _P ratio was paralleled with an equal decline in the corresponding fluorescence ratio F _V/F _M at 77K, and a similar decline in the maximum quantum yield of O₂ evolution, it is suggested that the decline in the F _V/F _P ratio represents a damage in photosyntem II attributable to photoinhibition. Recovery of the F _V/F _P ratio in dim light following a decline on a cloudless day took 7–16 h to go to completion; the F _V/F _P ratio was fully restored the following morning. When all active leaves of a peripheral shoot were compared, the F _V/F _P ratio in the afternoon of a day of bright light varied greatly from leaf to leaf, though the majority of leaves showed a decline. This variation was matched by a pronounced variation in intercepted photon flux density. When leaves developed in the shade were exposed to full sunlight by trimming of the stand an increased sensitivity to photoinhibition was observed as compared to peripheral leaves. The present study indicates that peripheral willow shoots experienced in the order of 10–20% photoinhibition during an appreciable part of their life. This occurred even though the environmental conditions were within the optimal range of photosynthesis and growth.Abbreviations and symbols F _O minimum fluorescence - F _P fluorescence at the peak of the induction curve obtained at normal ambient temperatures - F _V variable fluorescence - F _M maximum fluorescence obtained at 77K - PPFD photosynthetic photon flux density     

Gas exchange and blood gases of Puna teal (Anas versicolor puna) embryos in the Peruvian Andes

Oxygen consumption, air cell gases, hematology, blood gases and pH of Puna teal (Anas versicolor puna) embryos were measured at the altitude at which the eggs were laid (4150 m) in the Peruvian Andes. In contrast to the metabolic depression described by other studies on avian embryos incubated above 3700 m, O₂ consumption of Puna teal embryos was higher than even that of some lowland avian embryos at equivalent body masses. Air cell O₂ tensions dropped from about 80 toor in eggs with small embryos to about 45 toor in eggs containing a 14-g embryo; simultaneously air cell CO₂ tension rose from virtually negligible amounts to around 26 torr. Arterial and venous O₂ tensions (32–38 and 10–12 toor, respectively, in 12- to 14-g embryos) were lower than described previously in similarly-sized lowland wild avian embryos or chicken embryos incubated in shells with restricted gas exchange. The difference between air cell and arterial O₂ tensions dropped significantly during incubation to a minimum of 11 torr, the lowest value recorded in any avian egg. Blood pH (mean 7.49) did not vary significantly during incubation. Hemoglobin concentration and hematocrits rose steadily throughout incubation to 11.5 g · 100 ml^-1 and 39.9%, respectively, in 14-g embryos.Abbreviations PO₂ partial pressure gradient of O₂ - BM body mass - D diffusion coefficient - G gas conductance (cm³·s^-1·torr^-1) - conductance to water vapor - IP internal pipping of embryos - P _ACO₂ partial pressure of carbon dioxide in air cell - P _AO₂ partial pressure of oxygen in air cell - P _aCO₂ partial pressure of carbon dioxide in arterial blood - P _aCO₂ partial pressure of oxygen in arteries - P _H barometric pressure (torr) - PCO₂ partial pressure of carbon dioxide - P _IO₂ partial pressure in ambiant air - PO₂ partial pressure of oxygen - P _VCO₂ venous carbon dioxide partial pressure - P _VO₂ mixed venous oxygen partial pressure - SE standard error - VO ₂ oxygen consumption     

Arterial blood pressure during voluntary diving in the tufted duck,Aythya fuligula

Arterial blood pressure was monitored in voluntarily diving tufted ducks. Mean arterial blood pressure while diving increased during the pre-dive tachycardia, fell to resting levels on submersion, then gradually increased before peaking on surfacing. Estimated total peripheral resistance fell during the pre-dive and post-dive tachycardia, presumably to allow the oxygen stores to be loaded and replenished respectively and/or for carbon dioxide levels to be reduced. Changes in mean arterial blood pressure and total peripheral resistance suggest that peripheral vasoconstriction occurs in some vascular beds during a dive. An increase in arterial blood pressure (and therefore perfusion pressure) may be employed to increase blood flow and oxygen delivery to the active leg muscles.Abbreviations ecg Electrocardiogram, f _H, heart rate - MABP mean arterial blood pressure - P _b blood pressure(s) - TPR total peripheral resistance - V _b cardiac output     

Static Magnetic Field Versus Systemic Calcium Channel Blockade Effect on Microcirculation: Possible Mechanisms and Clinical Implementation

The goal was to compare static magnetic field (SMF, generated by Nd₂–Fe₁₄–B magnets) vasodilator capacity with verapamil (VER, a potent, clinically verified Ca²⁺ channel-blocking agent), aimed to assess SMF implementation in conditions with vascular ischemia. Skin microcirculatory blood flow measured by microphotoelectric plethysmogram was recorded in conscious rabbits after 40 min of 0.25 T SMF regional exposure to ear microvascular net (SMF-Vas, n = 20), or 0.35 T to carotid baroreceptors (SMF-Car, n = 14), and compared with that after 30 min VER intravenous infusion (20 µg/kg/min, n = 20). The principal finding is that SMF-Vas, SMF-Car, and VER significantly increased microcirculatory blood flow by 17.9 ± 9.58%, 22.6 ± 11.11%, and 30.5 ± 14.06% (mean ± SEM) respectively, and there was no significant difference between all three treatments (P = 0.986). Microvascular dilation was accompanied by significant decrease of blood pressure in VER and SMF-Car cases. The decrease of arterial baroreflex sensitivity in VER contrasted with its increase in SMF-Car, coupled with improved vessel sensitivity to nitric oxide (NO) dilatory effect. This suggests that SMF can have a strong vasodilator property tailored to address diabetic, mainly NO-deficient, neural, and myogenic microvascular dysfunction, especially employing both SMFs’ vasodilation synergy. Bioelectromagnetics. 2020;41:447–457. © 2020 Bioelectromagnetics Society.     

Membrane permeability coefficients of murine primary neural brain cells in the presence of cryoprotectant

Neural cells isolated from the brain have a number of research and clinical applications, including transplantation to patients with neurodegenerative conditions. Tissue supply is one of the major limiting factors to clinical transplantation. Cryopreservation of primary neural cells would improve supply, aid in organisation of transplantation surgery and facilitate research. To date, cryopreservation using standard methods has resulted in reduced yield and/or viability of primary neural tissue. In order to optimise freezing protocols specifically for such cells, the non-osmotic volume (V_b), water permeability (L_p) and permeability to cryoprotectant (P_cpa) were determined.Murine foetal brain tissue from the ganglionic eminence (GE), ventral mesencephalon (VM), or neocortical mantle (Ctx) was trypsinised to a single cell suspension. To determine V_b, cell volume was measured after exposure to anisotonic solutions of sucrose (150–1500 mOsmol/kg). L_p (μm/min.atm) and P_cpa (μm/s) were determined for GE cells by measuring cell volume during exposure to 1.5 mol/l cryoprotectant. Cell volume was determined using an electronic particle counting method.V_b was 27% for Ctx and GE, and 30% for VM. The osmotic response of GE cells was similar in the presence of propane-1,2-diol and dimethyl sulphoxide. In the presence of ethylene glycol, cell volume decrease was greater on initial exposure to cryoprotectant and recovery slower. Differences in L_p, but not P_cpa, were found between cryoprotectants.The present results provide key parameters for optimisation of freezing protocols for cryopreservation of primary foetal brain tissues for application in neural cell transplantation.     

Hypoxic cardiorespiratory reflexes in the facultative air-breathing fish jeju (Hoplerythrinus unitaeniatus): role of branchial O2 chemoreceptors

In one series of experiments, heart frequency (f _H), blood pressure (P _a), gill ventilation frequency (f _R ), ventilation amplitude (V _AMP) and total gill ventilation (V _TOT) were measured in intact jeju (Hoplerythrinus unitaeniatus) and jeju with progressive denervation of the branchial branches of cranial nerves IX (glossopharyngeal) and X (vagus) without access to air. When these fish were submitted to graded hypoxia (water PO₂ ~140, normoxia to 17 mmHg, severe hypoxia), they increased f _R , V _AMP, V _TOT and P _a and decreased f _H. In a second series of experiments, air-breathing frequency (f _RA), measured in fish with access to the surface, increased with graded hypoxia. In both series, bilateral denervation of all gill arches eliminated the responses to graded hypoxia. Based on the effects of internal (caudal vein, 150 μg NaCN in 0.2 mL saline) and external (buccal) injections of NaCN (500 μg NaCN in 1.0 mL water) on f _R , V _AMP, V _TOT, P _a and f _H we conclude that the O₂ receptors involved in eliciting changes in gill ventilation and associated cardiovascular responses are present on all gill arches and monitor the O₂ levels of both inspired water and blood perfusing the gills. We also conclude that air breathing arises solely from stimulation of branchial chemoreceptors and support the hypothesis that internal hypoxaemia is the primary drive to air breathing.     

Decreases in Amino Acid and Acetylcholine Metabolism During Hypoxia

Abstract: Hypoxia impairs brain function by incompletely defined mechanisms. Mild hypoxia, which impairs memory and judgment, decreases acetylcholine (ACh) synthesis, but not the levels of ATP or the adenylate energy charge. However, the effects of mild hypoxia on the synthesis of the glucosederived amino acids [alanine, aspartate, γ-amino butyric acid (GABA), glutamate, glutamine, and serine] have not been characterized. Thus, we examined the incorporation of [U-¹⁴C]glucose into these amino acids and ACh during anemic hypoxia (injection of NaNO₂), hypoxic hypoxia (15 or 10% O₂), and hypoxic hypoxia plus hypercarbia (15 or 10% O₂ with 5% CO₂). In general, the synthesis of the amino acids and of ACh declined in parallel with each type of hypoxia we studied. For example, anemic hypoxia (75 mg/kg of NaNO₂) decreased the incorporation of [U-¹⁴C]glucose into the amino acids and into ACh similarly. [Percent inhibition: ACh (57.4), alanine (34.4), aspartate (49.2), GABA (61.9). glutamine (59.2), glutamate (51.0), and serine (36.7)]. A comparison of several levels (37.5, 75, 150, 225 mg/kg of NaNO₂) of anemic hypoxia showed a parallel decrease in the flux of glucose into ACh and into the amino acids whose synthesis depends on mitochondrial oxidation: GABA (r= 0.98), glutamate (r= 0.99), aspartate (r= 0.96), and glutamine (r= 0.97). The synthesis of the amino acids not dependent on mitochondrial oxidation did not correlate as well with changes in ACh metabolism: serine (r= 0.68) and alanine (r= 0.76). The decreases in glucose incorporation into ACh and into the amino acids with hypoxic hypoxia (15% or 10% O₂) or hypoxic hypoxia with 5% CO₂ were very similar to those with the two lowest levels of anemic hypoxia. Thus, any explanation of the brain's sensitivity to a decrease in oxygen availability must include the alterations in the metabolism of the amino acid neurotransmitters as well as ACh.