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N Heisler

Publications and source records attributed to N Heisler.

At least 19 recordsLinked to original sources

Oxygen delivery to the fish eye: root effect as crucial factor for elevated retinal PO2.

Although the retina has one of the highest metabolic rates among tissues, certain teleost fishes lack any vascular supply to this organ which, in combination with the overall thickness of the organ, results in extremely long diffusion distances. As the only way to compensate for these obstacles, oxygen partial pressure (PO2) in the eyes of such fish is elevated far above atmospheric values. Although not supported by any direct evidence, the enhancement of PO2 is considered to be related to the Root effect, the release upon acidification of Hb-bound O2 into physical dissolution, possibly supported by counter-current multiplication similar to the loop of Henle. The present study evaluates the magnitude of intraocular PO2 enhancement under tightly controlled physiological conditions, to directly confirm the involvement of the Root effect on intraocular PO2 in the retina of rainbow trout Oncorhynchus mykiss. Intraocular PO2 was determined with special polarographic microelectrodes inserted into the eye. PO2 profiles established in vivo by driving electrodes through the entire retina yielded average PO2 values between 10 mmHg (1.3 kPa) at the inner retinal surface and 382 mmHg (50.9 kPa) close to the outer retinal limit (Bruch's membrane). According to estimates on the basis of the diffusion distances determined from sections of the retina (approximately 436 microm at the site of PO2 measurement) and literature data on specific oxygen consumption, the in vivo determined values would be sufficient to cover the oxygen demand of the retina with some safety margin. For a clear and direct in-tissue-test as to the involvement of the Root effect, an isolated in vitro eye preparation was established in order to avoid the problem of indirect blood supply to the eye from the dorsal aorta only via the pseudobranch, a hemibranch thought to modulate blood composition before entry of the eye. Any humoral effects (e.g. catecholamines) were eliminated by perfusing isolated eyes successively with standardized red blood cell (RBC) suspensions in Ringer, using trout (with Root) and human (lacking any Root effect) RBC suspension. To optimize perfusate conditions for maximal Root effect, the Root effect of trout RBCs was determined in vitro via graded acidification of individual samples equilibrated with standardized gas mixtures. During perfusion with trout RBC, PO2 at the outer retinal limit was 99 mmHg (13.2 kPa), but fell by a factor of 3.3 upon perfusion with human RBC in spite of higher total oxygen content (TO2 2.8 for trout vs 3.9 mmol l-1 for human RBC). Upon reperfusion with trout RBC, PO2 was restored immediately to the original value. This regularly observed pattern indicated a highly significant difference (P=0.003) between perfusion with trout (with Root effect; high retinal PO2) and perfusion with human (no Root effect; low retinal PO2) RBC suspension, thus clearly demonstrating that the Root effect is directly involved and a crucial prerequisite for the enhancement of PO2 in the retina of the teleost eye.

Animals↗

O(2)-dependent K(+) fluxes in trout red blood cells: the nature of O(2) sensing revealed by the O(2) affinity, cooperativity and pH dependence of transport.

The effects of pH and O(2) tension on the isotonic ouabain-resistant K(+) (Rb+) flux pathway and on haemoglobin O2 binding were studied in trout red blood cells (RBCs) in order to test for a direct effect of haemoglobin O(2) saturation on K(+) transport across the RBC membrane. At pH values corresponding to in vivo control arterial plasma pH and higher, elevation of the O(2) partial pressure (PO(2)) from 7.8 to 157 mmHg increased unidirectional K(+) influx across the RBC membrane several-fold. At lower extracellular pH values, stimulation of K(+) influx by O(2) was depressed, exhibiting an apparent pK(a) (pK'(a)) for the process of 8.0. Under similar conditions the pK'(a) for acid-induced deoxygenation of haemoglobin (Hb) was 7.3. When trout RBCs were exposed to PO(2) values between 0 and 747 mmHg, O(2) equilibrium curves typical of Hb O(2) saturation were also obtained for K(+) influx and efflux. However, at pH 7.9, the PO(2) for half-maximal K(+) efflux and K(+) influx (P50) was about 8- to 12-fold higher than the P(50) for Hb-O(2) binding. While K(+) influx and efflux stimulation by O(2) was essentially non-cooperative, Hb-O(2) equilibrium curves were distinctly sigmoidal (Hill parameters close to 1 and 3, respectively). O(2)-stimulated K(+) influx and efflux were strongly pH dependent. When the definition of the Bohr factor for respiratory pigments (Phi = delta logP50 x delta pH(-1)) was extended to the effect of pH on O(2)-dependent K(+) influx and efflux, extracellular Bohr factors (Phi(o) of -2.00 and -2.06 were obtained, values much higher than that for Hb (Phi(o) = -0.49). The results of this study are consistent with an O(2) sensing mechanism differing markedly in affinity and cooperativity of O(2) binding, as well as in pH sensitivity, from bulk Hb.

Acetates↗

Effects of anoxia on intracellular free Ca2+ in isolated cardiomyocytes from turtles.

One of the most important negative consequences of hypoxic stress in the mammalian myocardium is a breakdown in intracellular calcium homeostasis. This study examines the effects of anoxic stress on intracellular calcium regulation in isolated ventricular myocytes from a hypoxia tolerant vertebrate, the western painted turtle (Chrysemys picta bellii). Isolated calcium tolerant cardiomyocytes from turtle hearts were mounted on a glass cover slip that formed the bottom of a sealed, Plexiglas perfusion chamber. Free [Ca2+]i (determined by FURA2 fluorescence) in isolated turtle cardiomyocytes averaged 31.7 +/- 3.2 nM after 30 min of normoxic perfusion (20 degrees C, pHc = 7.77). This value is on the low end of the published range for mammalian cardiomyocytes. Perfusion with anoxic Ringer equilibrated with 3% CO2, resulted in a significant increase in free [Ca2+]i to 941 +/- 494.6 nM after 60 min. Increasing the CO2 in the perfusion solution to 5% or 6% blunted this rise (peak levels after 60 min of anoxia were 420.5 +/- 176.0 nM and 393.8 +/- 132.8 nM, respectively). A further increase to 8% CO2 increased the maximal value for free [Ca2+]i to 610.9 +/- 297.5 nM. In eight cells from the 5% CO2 protocol in which [Ca2+]i was monitored during recovery, reperfusion with normoxic Ringer rapidly lowered intracellular calcium to 92.8 +/- 9.7 nM within 15 min. Anoxia at relatively high extracellular (and hence intracellular) pH results in an increase in free [Ca2+]i comparable in magnitude and time course to that seen in some mammalian cardiomyocyte preparations. Perfusion of anoxic myocytes with Ringer equilibrated with either 5% or 6% CO2 blunted this increase in intracellular calcium, possibly an example of the pH paradox effect. A more severe combination of respiratory acidosis and anoxia (8% CO2) removed this protective effect.

Animals↗

Analysis of cardiac shunting in the turtle Trachemys (Pseudemys) scripta: application of the three outflow vessel model.

Blood distribution within the ventricle was analysed in acutely prepared turtles Trachemys scripta by measuring the oxygen concentration and flow rates of blood in the central vessels. Pulmonary (Qp) and systemic (Qs) blood flow rates were similar when total cardiac output (Qtot) was below 40 ml min-1 kg-1. Above this value, increments of Qtot were directed to the pulmonary circuit, with Qs levelling off at approximately 20 ml min-1 kg-1. When Qtot was larger than 40 ml min-1 kg-1, the systemic circuit was almost exclusively perfused by left atrial blood and systemic venous return was almost all directed towards the lungs. Blood oxygen levels and flow rates were consistently higher in the right aorta than in the left aorta. Blood movement within the ventricle, coupled with differences in ejection timing, is probably the decisive factor determining this pattern of blood distribution in the turtle heart.

Animals↗

The mechanism of cardiac shunting in reptiles: a new synthesis.

The mechanism of cardiac shunting in reptiles is controversial. Recent evidence suggests that a right-to-left shunt in turtles results primarily from a washout mechanism. The mechanism that accounts for left-to-right (L-R) shunting is unresolved. This study used haemodynamic analysis and digital subtraction angiography to determine the mechanism of L-R cardiac shunting in the turtle Trachemys (Pseudemys) scripta. Animals were instrumented with ultrasonic blood flow probes (Transonic Systems, Inc.) for the measurement of total pulmonary blood flow and total systemic blood flow. In addition, catheters were inserted into the common pulmonary artery (PA), the systemic arteries, the left atrium and right atrium. These catheters were used for the measurement of blood pressure or for the infusion of radio-opaque material. Haemodynamic conditions were altered by electrical stimulation of the afferent (VAF) or efferent vagal nerves or by infusion of vasoactive drugs. Under control conditions, the peak systolic pressure in the systemic arteries was slightly higher than that in the PA (30.6 versus 28.3 mmHg; 4.08 versus 3.77 kPa), whereas diastolic pressure in the PA was significantly less than that in the systemic arteries (9.8 versus 24.4 mmHg; 1.31 versus 3.25 kPa). During VAF stimulation, the peak systolic pressures in the PA and aortae almost doubled. Diastolic pressure in the systemic arteries also doubled, but it increased by only 45% in the PA. Ejection of blood into the PA preceded that into the left aorta by 53 ms under control conditions. This difference increased (by as much as 200 ms) as the difference in the diastolic pressures between the two circulations increased during VAF stimulation. This resulted in the development of a large net L-R shunt. Under these conditions, digital subtraction angiography showed that the L-R shunt resulted from a combination of both washout and pressure mechanisms.

Angiography, Digital Subtraction↗

Extracellular and intracellular carbon dioxide concentration as a function of temperature in the toad Bufo marinus.

Previous studies of reptiles and amphibians have shown that changing the body temperature consistently produces transient changes in the respiratory exchange ratio (RE) and, hence, changes in whole-body CO2 stores, and that the extracellular fluid compartment contributes to the temperature-related changes in CO2 stores. The purpose of this study was to determine whether the intracellular fluid compartment contributes to the changes in CO2 stores in undisturbed resting cane toads. Increasing body temperature from 10 to 30 degrees C temporarily elevated RE, and returning body temperature to 10 degrees C temporarily lowered RE. The estimated average change in whole-body CO2 stores associated with the transient changes in RE was 1.0 +/- 0.8 mmol kg-1 (+/- S.D., N = 6). Plasma [CO2] and, thus, extracellular fluid [CO2], were unaffected by the temperature change. Plasma calcium levels were also unaffected, so that bone CO2 stores did not contribute to changes in whole-body CO2 stores. Intracellular [CO2] was determined for the lung, oesophagus, stomach, small intestine, liver, ventricle, red blood cells, skin and 14 skeletal muscles. [CO2] was significantly lower (P < 0.05) at higher temperature in 10 of these, and seven others, although not statistically significant (P > 0.05), had mean values at least 0.5 mmol kg-1 lower at the higher temperature. The average change in intracellular [CO2] for all tissues examined was -0.165 mmol kg-1 degrees C-1. We conclude that, in cane toads, the temperature-related transients in RE result from intracellular CO2 adjustments, that different tissues have unique intracellular CO2/temperature relationships, and that a combination of respiratory and ion-exchange mechanisms is used to adjust pH as temperature changes.

Acid-Base Equilibrium↗

Effect of chronic hypoxia on hemodynamics, organ blood flow and O2 supply in rats.

Aortic blood flow, heart rate, blood pressure and blood flow distribution were measured in 10 chronically hypoxic rats (3 weeks, PB 370-380 Torr) breathing 10% O2 (chronic hypoxia) and after 30 min of breathing air (acute normoxia). Controls were 10 normoxic littermates breathing air (normoxia) and 10% O2 for 30 min (acute hypoxia). Acute hypoxia resulted in increased aortic blood flow and heart rate, and decreased total peripheral resistance. Blood flow and oxygen supply to vital organs increased, indicating that blood flow redistribution plays an important role in oxygen supply. In chronic hypoxia, aortic blood flow and heart rate remained elevated, and total peripheral resistance remained decreased. Blood flow distribution returned towards normoxia levels. Oxygen supply was maintained via increased arterial oxygen concentration. Acute normoxia resulted in decreased aortic blood flow and heart rate, and increased blood pressure and total peripheral resistance. Blood flow distribution was similar to that of chronic hypoxia except skeletal muscles, in which blood flow decreased markedly. Oxygen supply remained unchanged or increased.

Acid-Base Equilibrium↗

Regional blood flow in conscious resting rats determined by microsphere distribution.

To determine organ blood flow in the resting state, a box was designed to keep conscious untrained rats minimally disturbed. Blood pressure, heart rate, and organ blood flow, determined by the microsphere distribution and reference sampling technique, were measured in 11 Sprague-Dawley rats. After an acclimation period, 15-microns-diameter microspheres labeled with 113Sn were infused into the ascending aorta, a reference blood sample was withdrawn from the caudal artery, and organ blood flows were computed according to standard procedures. The average values of heart rate (365 beats/min) and blood flow to the brain (45 ml.min-1.100 g-1) and hindlimb muscles (15 ml.min-1.100 g-1) were significantly lower than most values reported earlier, whereas splanchnic blood flow was significantly higher (106 ml.min-1.100 g-1). Blood flow to the soleus muscle, which is considered the most active for postural maintenance, was relatively high (99 ml.min-1.100 g-1). The combination of low skeletal muscle and high visceral blood flows observed in these experiments suggests a low sympathetic tone, which is consistent with the low level of circulating catecholamines also observed in this study. It is hypothesized that the difference between our present and previous results is a lower level of stress, attributable to a more complete acclimation to the experimental environment.

Animals↗

Changes in regional blood flow distribution and oxygen supply during hypoxia in conscious rats.

The effects of acute hypoxia on central hemodynamics, regional blood flow, and regional oxygen supply (blood flow x arterial O2 concentration) were studied in conscious resting rats. Regional blood flow was determined by the radiolabeled microsphere technique. Blood pressure, heart rate; and aortic blood flow increased and total peripheral resistance decreased significantly during hypoxia. Blood flow to brain, respiratory muscles, and liver increased both in absolute value and as a fraction of the aortic blood flow. Fractional blood flow to the gastrointestinal tract, spleen, pancreas, skin, fat, and hindlimb bones decreased during hypoxia; blood flow decreased in absolute values only in stomach and fat. Oxygen supply to brain, respiratory muscles, and liver increased during hypoxia, whereas it decreased in the remaining organs investigated.

Animals↗

Spatial and temporal variability of blood flow in stimulated dog gastrocnemius muscle.

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply of gastrocnemius muscles (mean weight 88 g) subsequently cut into 0.5 g pieces for determination of radioactivity. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 microns and 15 microns microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 microns microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 (= square root of 0.45(2) - 0.12(2)), but there were marked differences between muscles. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 minutes into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19. There were large differences between muscle pieces within a muscle and between muscles. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.

Animals↗

Regulation of ventilation and acid-base status in the elasmobranch Scyliorhinus stellaris during hyperoxia-induced hypercapnia.

Exposure of the elasmobranch Scyliorhinus stellaris to environmental hyperoxia (PO2 of 500 mm Hg) resulted in a considerable rise of arterial PCO2 from 1.9 mm Hg during normoxia to about 11 mm Hg after 6 days as an expression of the primarily oxygen-oriented regulation of gill ventilation. In contrast to the typical pattern during environmental hypercapnia, however, arterial plasma pH was hardly affected by the considerable hyperoxia-induced hypercapnia. At elevated arterial PO2 values (200-300 mm Hg) gill ventilation was apparently not adjusted exclusively for the oxygen demands of the organism, but was matched to the requirements of acid-base regulation such that the rise in PCO2 could be compensated for by a net gain of bicarbonate-equivalent ions from the environment. This fine adjustment of gill ventilation to the bicarbonate-equivalent uptake rate extended the process of adaptation to about 6 days and resulted in an almost complete pH compensation during the entire process of PCO2 increase. These data suggest that during conditions of reduced oxygen-related respiratory drive the regulation of gill ventilation is primarily dependent upon the acid-base parameters.

Acid-Base Equilibrium↗

Analysis of intracardiac shunting in the lizard, Varanus niloticus: a new model based on blood oxygen levels and microsphere distribution.

The central sites of the cardiovascular system (right and left aortic arches, RAo and LAo, pulmonary artery, PA, and right and left atria, RAt and LAt) were chronically and non-occlusively cannulated for an analysis of intracardiac shunting in Varanus niloticus. Oxygen partial pressure (PO2) and oxygen concentration (CO2) were significantly higher in right aortic blood than values determined in left aortic blood. The difference was larger in animals acclimated to 25 degrees C (RAo CO2 = 4.5 +/- 1.00 vol %, LAo CO2 = 3.8 +/- 1.14, X +/- SD, n = 19) than at 35 degrees C (RAo CO2 = 5.8 +/- 1.24, LAo CO2 = 5.4 +/- 1.35, n = 18) (P less than 0.001 for both temperatures, paired t-test). These data are explained by a new model describing the differential shunting patterns of the two aortae in addition to the conventional overall right-to-left and left-to-right shunt fractions. This model was solved on the basis of blood gas data collected by simultaneous multiple-site gas analysis, together with data on the differential blood flow in the central vascular system, collected by application of the microsphere method. At 35 degrees C both right-to-left and left-to-right shunts were relatively small (about 9%), with the right-to-left shunt fraction directed exclusively into the left aorta. Thus right aortic blood represented left atrial blood, whereas left aortic blood was composed of 80% left atrial and 20% right atrial blood. Ninety percent of the pulmonary arterial blood was derived from the right atrium and 10% from the left atrium. At 25 degrees C the composition pattern of effluent blood for each vessel was similar, the absolute flow distribution, however, was different from that at 35 degrees C. These findings are discussed with respect to their significance and compatibility with the wash-out shunt model.

Animals↗

Blood flow distribution and its temporal variability in stimulated dog gastrocnemius muscle.

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply in 8 gastrocnemius muscles (mean weight 84 g) of 6 anesthetized dogs (20-25 kg body weight). The distribution of 10 micron microspheres in regions of about 0.5 g was very similar to that of the standard 15 micron microspheres, whereas that of 25 micron microspheres was more uneven. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 micron and 15 micron microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 micron microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 ( = square root 0.45(2) - 0.12(2], but there were marked differences between muscles. At equal blood flow levels, the inhomogeneity during reactive hyperemia was similar to that observed during stimulation. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 min into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19, but the differences in the extent of temporal blood flow changes among muscle pieces within a muscle and between different muscles were large. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.

Animals↗

Acid-base regulation and blood gases in the anuran amphibian, Bufo marinus, during environmental hypercapnia.

Specimens of Bufo marinus were exposed to aerial and aquatic hypercapnia (5% CO2) in a closed, water recirculation system to evaluate mechanisms involved in the compensation of a respiratory acidosis in these animals. Arterial PCO2 was elevated from about 9 mmHg (1 mmHg = 133.3 Pa) to 35 (1 h) and 37 mmHg (2 h), and gradually approached about 40 mmHg (24 h of hypercapnia). The typical hypercapnia-induced reduction in plasma pH from about 7.9 to below 7.4 was partially offset, at least during the first hours of hypercapnia, by a reduction in the inspired/arterial PCO2 difference, presumably brought about by pulmonary hyperventilation. The predominant contributor to extracellular pH compensation, however, was a net gain of bicarbonate from the environment, mainly facilitated by ammonia excretion. Bicarbonate originating from the environment was accumulated in the body fluids, increasing the plasma concentration from the control of about 9 to 36 mmol l-1 after 24 h. Extracellular pH was compensated to only about 30% of the shift expected at constant bicarbonate level and, according to the steady reduction of pH, non-bicarbonate buffering of CO2 also contributed significantly to the elevation of bicarbonate. This relatively poor pH compensation (compared with fishes) could not be improved either by direct administration of bicarbonate into the bloodstream or by increased environmental ion concentrations. It is concluded that the availability of bicarbonate is not a limiting factor for pH compensation during hypercapnia, and that the inability of Bufo to accumulate bicarbonate to concentrations sufficient for better hypercapnia compensation is based on a constitutional 'bicarbonate threshold' of the resorbing and retaining structures for acid-base-relevant ions.

Acid-Base Equilibrium↗

Blood flow patterns in the salamander, Ambystoma tigrinum, before, during and after metamorphosis.

The patterns of blood flow through the complex circulation of the tiger salamander, Ambystoma tigrinum, were investigated during aquatic normoxia and hypoxia by application of the microsphere technique. The distribution of differently labelled microspheres injected into the bloodstream towards the left and right atria, respectively, was used to evaluate the role of the ductus arteriosus in lung perfusion before, during and after metamorphosis, as well as the general contribution of right and left atrial outputs to the blood flow in gills and lungs in neotenic and postmetamorphic animals. The distribution patterns of radioactive microspheres among pulmonary, branchial and systemic tissues indicated that the ductus arteriosus is the major pulmonary perfusion pathway in neotenic and metamorphosing animals, whereas after metamorphosis the main perfusion pathway is down the entire length of the pulmonary artery. In neotenes, the ductus arteriosus becomes even more important during aquatic hypoxia. The anterior branchial arches receive blood richer in pulmonary venous blood than the posterior arches. Approximately 26% of left atrial output and 36% of right atrial output perfuses the brachial respiratory lamellae during normoxia in neotenes. Severe aquatic hypoxia appears to increase the fraction of cardiac output flowing to the lung and decrease the fraction flowing into the first branchial arch in neotenes. This decrease into the first arch may facilitate lung perfusion and also reduce branchial O2 loss. In postmetamorphic animals, approximately 55% of right atrial output and 32% of left atrial output is directed to the lungs. The flow patterns in postmetamorphic animals remain unaffected by aquatic hypoxia.

Ambystoma↗

In vivo analysis of partitioning of cardiac output between systemic and central venous sinus circuits in rainbow trout: a new approach using chronic cannulation of the branchial vein.

Freshwater-acclimated rainbow trout were chronically and non-occlusively cannulated in the dorsal aorta (DA), sinus venosus (SV) and branchial vein (BV), the latter returning the blood perfusing the central venous sinus (CVS) of the gill after being shunted away from the systemic circuit. After recovery, blood samples from these three sites were analysed for haematocrit (Hct) and [Hb]. Branchial venous blood was found to have considerably lower Hct and [Hb] (Hct = 3.5 +/- 3.1%; [Hb] = 1.04 +/- 0.75 g 100 ml-1) than systemic blood (DA: Hct = 24.3 +/- 8.9%, [Hb] = 6.54 +/- 2.90 g 100 ml-1; SV: Hct = 23.1 +/- 8.8%, [Hb] = 6.15 +/- 2.55 g 100 ml-1; means +/- S.D. N = 8), which strongly suggests that plasma skimming occurred at arteriovenous anastomoses and arterioles draining into the CVS. The partitioning of cardiac output, calculated on the basis of the [Hb] data, showed that the systemic flow accounted for 93 +/- 4.6% (N = 7) of the total cardiac output with only 7 +/- 4.7% of cardiac output being diverted into the CVS, thus bypassing the systemic vasculature. Previous results using in vitro experiments are compared with the present data in an evaluation of the usefulness of the isolated perfused gill and head preparations in the experimental analysis of circulatory physiology in fish gills.

Animals↗

Effects of nitrite exposure on blood respiratory properties, acid-base and electrolyte regulation in the carp (Cyprinus carpio).

Adult carp were subjected to 1 mM environmental nitrite for 48 h and nitrite uptake and changes in blood respiratory properties, extracellular electrolyte composition and acid-base status were examined. A constant influx of nitrite caused an accumulation of NO2- in plasma to 5.4 mM in 48 h. The fraction of methaemoglobin rose with plasma [NO2-] to 83%, and the arterial oxygen content decreased to extremely low values. Arterial PO2 increased as a compensation to this O2-shortage, whereas the O2 saturation of the functional (unoxidized) haemoglobin decreased, revealing a reduction in its O2 affinity. Blood haematocrit decreased as a result of red cell shrinkage, which caused very high red cell haemoglobin (Hb) concentrations. The erythrocytic nucleoside triphosphate (NTP) concentration showed a parallel increase whereby NTP/Hb, as well as the relative contributions of ATP and GTP to NTP, remained unchanged. Plasma [Cl-] declined by 15 mM in 48 h, offsetting the plasma [NO2-] increase, minor changes in plasma [HCO3-] and a considerable increase in plasma [lactate]. Arterial pH and [HCO3-] rose slightly during the first 24 h of nitrite exposure, but returned to control values at 48 h. The rise in plasma [lactate] was not reflected in an extracellular metabolic acidosis. Plasma [K+] increased by 94% in 48 h, revealing an uncompensated extracellular hyperkalemia, whereas plasma [Na+] decreased, and plasma [Ca++] was unchanged. Plasma osmolality remained essentially constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗