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Biomedical subjects

N Heisler

Publications and source records attributed to N Heisler.

At least 37 records · Page 2Linked to original sources
PubMed1987

In vivo measurements of tissue pH of the heart, brain, liver, spleen, and skeletal muscle following therapy of severe metabolic uraemic acidosis with infusion of bases: an experimental study on the limitation of the Mellemgaard-Astrup equation.

The intracellular tissue pH of the heart, brain, liver, spleen, and skeletal muscle of nephrectomized rats was determined in vivo from the distribution of 14C-labelled DMO (5,5-dimethyl-2-4-oxazolidinedione) following acute variation of arterial plasma pH (pHe) by CO2 inhalation or sodium bicarbonate administration in the range of pHe 6.9-7.7, or following correction of severe metabolic uraemic acidosis with sodium bicarbonate or Tris (hydroxymethyl) aminomethane (THAM) infusion according to the Mellemgaard-Astrup equation. It was found that: (a) during severe uraemic acidosis administration of sodium bicarbonate according to the Mellemgaard-Astrup equation leads to a stable correction of the extracellular disturbance while a comparable amount of THAM has a less pronounced effect; (b) in the first 60-120 min following therapy of severe chronic uraemic acidosis there is an overcorrection of intracellular tissue pH when compared to acute acidosis of the same degree. PHi of the investigated tissues increased more following sodium bicarbonate administration than following THAM; (c) the amount of base required for the correction of the overall acid-base status of the organism cannot be determined from the extracellular measurements alone; (d) when the normal acid-base correlation between blood and tissues is disturbed, measurements of arterial acid-base parameters can give misleading information about the whole body acid-base status and may result in failure of therapy.

Acid-Base Equilibrium↗
PubMed1987

Respiratory properties of blood and arterial blood gases in the tegu lizard: effects of temperature and hypercapnia.

The effects of body temperature and hypercapnia (7% inspired CO2) on arterial blood gases, plasma pH, and the characteristics of the blood oxygen dissociation curve were determined in Tegu lizards (Tupinambis nigropunctatus). Arterial pH fell from 7.59 to 7.50 when body temperature was increased from 25 to 35 degrees C. The pH/temperature coefficient (delta pH/delta t = -0.009 U/degrees C) was half of that predicted on the basis of 'constant relative alkalinity' and the alphastat hypothesis. The fall in plasma pH resulted from a decrease in plasma [HCO3-], and a rise in plasma Pco2. The O2 affinity of Tegu blood, expressed by the partial pressure at half saturation (P50), decreased with temperature in vitro from 42.3 to 49.6 torr at pH 7.4. The apparent enthalpy (delta H = -3.1 kcal/mol) is about 1/4 of that of human blood. In vivo, the arterial blood oxygen saturation decreased from 89% at 25 degrees to 82% at 35 degrees C. Arterial Po2 increased from 61 to 71 torr as expected from the right-shift of the oxygen dissociation curve. During environmental hypercapnia (7% CO2, 21% O2, 72% N2 inspired concentrations), arterial pH decreased to 7.28. Arterial O2 saturation remained constant and arterial Po2 increased from 61 to 85 torr due to the right-shift of the oxygen dissociation curve. The comparatively small effect of changes in temperature on the oxygen affinity of Tegu blood (directly according to the delta H value, and indirectly via changes in blood pH) results in a relatively small right shift of the oxygen dissociation curve, and accordingly in relatively high arterial and tissue Po2 values also at higher temperatures.

Animals↗
PubMed1986

Distribution of tris buffer between intracellular and extracellular space as a function of plasma pH in the rat.

Rats were anaesthetized with halothane and artificially ventilated. After bilateral nephrectomy and implantation of arterial and venous catheters, arterial plasma pH (pHe) was adjusted by infusion of HCl or sodium bicarbonate to 7.2, 7.4, or 7.5 and kept constant throughout the experiment. The distribution of tris between intra- and extracellular compartments was determined as a function of time up to 24 h after infusion of 14C-labelled tris and 3H inulin in five skeletal muscle groups, heart, liver, spleen, and brain tissue. The following results were obtained: Tris diffuses very slowly into the intracellular space of the investigated tissues. For different arterial plasma pH, the intracellular tris concentration is quite different. It rises more rapidly and reaches higher levels in alkalemia. Five different skeletal muscle groups showed the same rates of rise of intracellular tris at the same pHe. Tris diffuses almost immediately into liver cells, the rates being slower in spleen, heart, skeletal muscle and brain, in that order. Only in the liver did intracellular tris concentration reach a steady state, at levels higher than theoretically predicted, suggesting that ionic tris also is permeable. In other tissues, lack of steady states at the end precluded similar conclusions. It can be concluded that the clinical importance of tris therapy is in its elimination of H+ ions from the extracellular space and in the generation of bicarbonate that then penetrates the intracellular compartment.

Animals↗
PubMed1986

Correction of metabolic alkalosis by HCl and acetazolamide: effects on extracellular and intracellular acid-base status in rats in vivo.

Extracellular plasma pH (pHe) of nephrectomized male or female Sprague-Dawley rats was changed by infusion of either sodium bicarbonate or HCl to predetermined values in the pH range of 7.53-7.14, and then held constant for 2 h. Intracellular pH (pHi) of the liver, heart, brain, and two skeletal muscle groups as calculated from the distribution of 14C-labelled DMO (5.5-dimethyl-2,4-oxazolidinedione) was compared to corresponding tissues of a control group and rats treated with the carbonic anhydrase inhibitor acetazolamide (Diamox). When compared to control, changes of the extracellular pH in male or female rats were followed by similar effects on pHi in the investigated tissues. At the same extracellular pH there were no statistical differences between pHi values of HCl or acetazolamide treated rats, though the arterial PCO2 following acetazolamide administration was significantly increased when compared to control or the corresponding HCl group. This study shows that administration of acetazolamide or HCl results in a dose-dependent decrease of plasma and tissue pH, and that both agents may be used as a logical and safe therapy during severe metabolic alkalosis in rats.

Acetazolamide↗
PubMed1986

The relative distribution of pulmocutaneous blood flow in Rana catesbeiana: effects of pulmonary or cutaneous hypoxia.

The distribution of pulmocutaneous heart output to lungs and skin was determined in non-anaesthetized, fully recovered bullfrogs (Rana catesbeiana) by application of the microsphere method in order to study the modulation of blood flow to different gas exchange sites in amphibians during environmental air and water hypoxia. The relative perfusion of various skin areas was found to be rather heterogeneously distributed with an over-proportionately high blood flow to the ventral body surface. This distribution of flow among different skin areas remained unaffected by any type of environmental hypoxia. The relative perfusion of lungs and skin, however, was significantly affected by the pattern of environmental oxygen partial pressure. The relative lung perfusion (approximately equal to 80% of pulmocutaneous flow in normoxic control conditions) was increased during water hypoxia, and reduced with lowered inspired PO2. This mechanism could be interpreted as a readjustment of blood flow towards the gas exchange site with higher oxygen partial pressure, but may also represent a mechanism to prevent oxygen loss from the body stores at gas exchange sites of low oxygen tension.

Animals↗
PubMed1986

Acid-base regulation and ion transfers in the carp (Cyprinus carpio): pH compensation during graded long- and short-term environmental hypercapnia, and the effect of bicarbonate infusion.

To study both temporal and quantitative effects of hypercapnia on the extent of pH compensation in the arterial blood, specimens of carp (Cyprinus carpio) were exposed to a PCO2 of about 7.5 mmHg (1 mmHg = 133.3 Pa) (1% CO2) in the environmental water for several weeks, and a second group of animals was subjected to an environmental PCO2 of about 37 mmHg (5% CO2) for up to 96 h. A third series of experiments was designed to test the possibility that infusion of bicarbonate would increase the extent of plasma pH compensation. Dorsal aortic plasma pH, PCO2 and [HCO3-], as well as net transfer of HCO3- -equivalent ions, NH4+, Cl- and Na+, between fish and ambient water, were monitored throughout the experiments. Exposure to environmental PCO2 of 7.5 mmHg resulted in the expected respiratory acidosis with the associated drop in plasma pH, and subsequent compensatory plasma [HCO3-] increase. The compensatory increase of plasma bicarbonate during long-term hypercapnia continued during 19 days of exposure with plasma bicarbonate finally elevated from 13.0 mmoll-1 during control conditions to 25.9 mmoll-1 in hypercapnia, an increase equivalent to 80% plasma pH compensation. Exposure to 5% hypercapnia elicited much larger acid-base effects, which were compensated to a much lesser extent. Plasma pH recovered to only about 45% of the pH depression expected at constant bicarbonate concentration. At the end of the 96-h exposure period, plasma [HCO3-] was elevated by a factor of 2.5 to about 28.2 mmoll-1. The observed increase in plasma bicarbonate concentration during 5% hypercapnic exposure was attributable to net gain of bicarbonate equivalent ions from (or release of H+-equivalent ions to) the environmental water. Quantitatively, the gain of 15.6 mmol kg-1 was considerably larger than the amount required for compensation of the extracellular space, suggesting that acid-base relevant ions were transferred for compensation of the intracellular body compartments. The uptake of bicarbonate-equivalent ions from the water was accompanied by a net release of Cl-and, to a smaller extent, by a net uptake of Na+, suggesting a 75% contribution of the Cl-/HCO-3 exchange mechanism. Infusion of bicarbonate after 48 h of exposure to 7.5 mmHg PCo2 had only a transient effect on further pH compensation. The infused bicarbonate was lost to the ambient water, and pre-infusion levels of bicarbonate were reattained within 24 h. Repetition of the infusion did not result in a notable improvement of the acid-base status.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid-Base Equilibrium↗
PubMed1985

Oxygen consumption and mode of energy production in the intertidal worm Sipunculus nudus L.: definition and characterization of the critical PO2 for an oxyconformer.

Oxygen consumption, anaerobic metabolism, and oxygen supply of inner tissues were analysed in Sipunculus nudus at different oxygen tensions. Oxygen consumption, energy expenditure, and the PO2 in the coelomic fluid decreased linearly with declining ambient PO2. Below a certain range of PO2, which was a function of the size of the animals, the rate of oxygen consumption deviated progressively from the linear PO2/MO2 function. In the same range of ambient PO2 the coelomic PO2 levelled off. Anaerobic glycolysis, phosphagen degradation, and the succinate-propionate pathway became apparent with concentration changes of anaerobic metabolites first occurring in inner tissues. In extension of the conventional definition (Prosser, 1973; Dejours, 1981) the term critical PO2 (Pc) is applied to the oxyconforming Sipunculus nudus. The Pc is redefined as the steady-state PO2 below which environmental oxygen availability becomes insufficient for complete aerobic metabolism (as indicated by the onset of anaerobic energy production). It is discussed to be closely linked to the oxygen supply of inner tissues. This redefined critical PO2 is shifted to higher partial pressures with increasing size of the animals because of the diffusion distance related decrease in coelomic PO2. Accordingly, with decline of ambient PO2, oxygen starts to be released from haemerythrin at higher ambient PO2 values in larger animals. The pigment, which is likely to function as an oxygen store, defers anaerobiosis and, thereby, supports compensation of a higher Pc in large individuals by means of an increased haematocrit. The Pc is discussed as crucial factor for survival of individual animals in intertidal oxygen-depleted environments.

Aerobiosis↗
PubMed1985

Blood flow distribution in dog gastrocnemius muscle at rest and during stimulation.

The distribution of blood flow within the isolated perfused dog gastrocnemius muscle (weight 100-240 g) was studied by intra-arterial injection of radioactively labeled microspheres (diameter 15 micron) at rest and during supramaximal stimulation to rhythmic isotonic tetanic contractions of varied frequency against varied loads. After the experiment the muscle was cut into 180-250 pieces of approximately 0.75 g each, and the blood flow to each muscle piece was determined from its radioactivity. The inhomogeneity of blood flow was represented as the frequency distribution of the ratios of regional specific blood flow, i.e., blood flow per unit tissue weight of the piece, QR, to the overall specific blood flow of the muscle, Q. The QR/Q values for the individual pieces of a muscle were found to vary widely both at rest and during stimulation. With rising work load the frequency distribution had a tendency to broaden and flatten, indicating increasing perfusion inhomogeneity. On the average of the experiments, there was no significant difference in specific blood flow between the three anatomic components of the gastrocnemius (lateral and medial heads of gastrocnemius and flexor digitorum superficialis) nor between the superficial and deep portions within these anatomic components, only the distal third of the muscle was relatively less perfused compared with the proximal two-thirds. The considerable inhomogeneity of blood flow as revealed by microsphere embolization and by other methods is expected to exert important limiting effects on local O2 supply, particularly during exercise. Its neglect would lead to serious errors in the analysis of O2 supply to muscle tissue.

Animals↗
PubMed1985

Effect of sodium bicarbonate and Tris (THAM) infusion on intra- and extracellular acid-base status during experimental uremia in the rat.

The intra- and extracellular acid-base status of nephrectomized rats was determined following infusion of 10 mmol/kg body mass Tris (THAM) or sodium bicarbonate. The 'mean whole body pHi', an overall estimate of the intracellular pH (complementary to the in vivo determined arterial plasma pH) was calculated from the distribution of 14C-labelled 5,5-dimethyl-2,4-oxazolidinedione. For evaluation of buffer effect of Tris or sodium bicarbonate, extra- and intracellular bicarbonate concentration was calculated from the Henderson-Hasselbalch equation. Intracellular and extracellular pH and bicarbonate concentration were significantly more increased when sodium bicarbonate was infused, while PCO2 increased significantly more when Tris was administered. On the basis of these results it is concluded that treatment of both in intracellular and extracellular uremic acidosis can be performed more efficiently with bicarbonate than with Tris buffer.

Acid-Base Equilibrium↗
PubMed1984

Role of ion transfer processes in acid-base regulation with temperature changes in fish.

The contributions of transmembrane and transepithelial ion transfer processes and of nonbicarbonate buffering to the in vivo acid-base regulation have been evaluated. Model calculations were performed utilizing experimental data on transepithelial transfer of ions relevant for the acid-base regulation, the intracellular buffering properties of fish tissues, and the behavior of intracellular and extracellular pH and bicarbonate concentration with changes of temperature. The results of these studies indicate that the changes in the pK values of physiological nonbicarbonate buffers with changes in temperature support the adjustment of pH to lower values with rising temperature; however, transmembrane and transepithelial ion transfer mechanisms determine the acid-base regulation of intracellular and extracellular compartments.

Acid-Base Equilibrium↗
PubMed1984

Blood flow in exercising muscles by xenon clearance and by microsphere trapping.

The accuracy of muscle blood flow measurement by the 133Xe clearance method (QXe) was assessed against direct venous outflow (Qv) and microsphere trapping flow (Q mu) determinations in isolated perfused dog gastrocnemius both at rest and during graded stimulation [O2 consumption (VO2) up to 12 ml X 100 g-1 X min-1] and in the gastrocnemius, vastus lateralis, and triceps of intact dogs at rest and while running on a treadmill at varied speeds up to maximum VO2. In 29 measurements performed in 11 isolated muscles, Q mu was in good agreement with Qv at rest and at all stimulation levels (Q mu/Qv = 1.0; r = 0.98). 133Xe clearance yielded much lower blood flows than the venous outflow and the microsphere trapping methods. In 43 measurements in 11 muscles, the mean QXe/Qv ratio was 0.57 +/- 0.03 (SE), independent of blood flow. Similarly, in 65 measurements in 2 intact dogs, the mean QXe/Q mu ratio in all tested muscles was 0.49 +/- 0.02 (SE), independent of blood flow. These results show that the 133Xe clearance method considerably underestimates blood flow in dog muscles.

Animals↗
PubMed1984

[Kinetics of THAM (TRIS) distribution in intra- and extracellular compartments].

The distribution of 14C labelled THAM (tris-hydroxymethylaminomethane) was determined between intra- and extracellular space of nephrectomised Sprague-Dawley rats as a function of time at constant plasma pH of 7.4. The following results were obtained: An equilibrium in the distribution of THAM between ECS and ICS will not occur before 6-12 hours after administration. This indicates that THAM permeates very slowly into the intracellular compartment, which is in contrast to the general assumption that it quickly diffuses into the intracellular space to restore the intracellular acidosis. THAM disappears from the extracellular space in a multiexponential fashion, indicating that it equilibrates with the different body tissues at largely variable rates. The equilibrium which occurs between both body compartments 6-12 hours after THAM application does not agree with the values which are expected for transfer of only the nonionised substance. At plasma pH 7.4 and a "mean whole body pHi" of 6.88, THAM is distributed with a distribution ratio of 4 (ICS/ECS), a value quite different from the value of 11 which would be expected for exclusive nonionic diffusion. Thus THAM is also transferred across the cell membrane in ionised form. These results indicate that the influx of THAM into the intracellular space is too slow (when compared to the renal elimination kinetics) to influence intracellular pH significantly by direct buffer action. Moreover, only a fraction of THAM enters the intracellular space in the nonionised form, thus reducing (to an even greater extent) the direct effect of THAM on the intracellular acid-base equilibrium.

Animals↗
PubMed1983

Branchial ion exchange and acid-base regulation after strenuous exercise in rainbow trout (Salmo gairdneri).

Specimens of rainbow trout (Salmo gairdneri) were electrically stimulated to exhausting activity in a closed water recirculation system and the changes in dorsal aortic plasma pH, PCO2, PO2, O2 content, [Na+], [Cl-], [K+], [Lactate-] and Ht were measured during a 24 h recovery period. Net transfer of H+, Na+, Cl- and ammonia between fish and environment were determined by measurement of the concentration changes in the recirculating water. Strenuous exercise resulted in a severe lactacidosis which was corrected by transient net transfer of H+ ions to the environmental water within 4 h, about 6-8 h before the lactate was metabolically removed. The net transfer of H+ ions was achieved in part by branchial HCO3-/Cl- ion exchanges, but to a larger extent by branchial exchange of H+ and/or NH4+ against Na+. The excretion of ammonia, which was considerably enhanced during the first 4 h after exercise, was at least partially due to non-ionic diffusion across the gill epithelium. The observed elevation in ammonia excretion was probably the result of an exercise-induced increase in nitrogen metabolism rather than of production of ammonia for the purpose of acid-base regulation.

Acid-Base Equilibrium↗
PubMed1983

Intracellular and extracellular acid-base and electrolyte status of submerged anoxic turtles at 3 degrees C.

Specimens of fresh water turtles (Chrysemys picta bellii) were acclimated to 3 degrees C and then submerged in completely anoxic water for time periods of up to 12 weeks. Blood withdrawn via indwelling arterial catheters was analysed for plasma pH, PCO2, bicarbonate concentration, [lactate], [Na+], [K+], [Ca2+] and [Mg2+], and tissue samples of skeletal muscle, liver and cardiac muscle were excised. Samples of skeletal muscle were analysed for intracellular pH (DMO), [lactate], [Na+], [K+], [Ca2+], and [Mg2+], and samples of liver and cardiac muscle for intracellular pH and [lactate] during normoxia and after 1, 2, 4, 8 and 12 weeks of anoxia. Arterial plasma pH fell from 8.0 during normoxia to lower than 7.2 concomitant with a reduction in plasma [HCO3-] after 12 weeks of anoxia due to the production of large amounts of lactic acid. The intracellular pH (pHi) of heart muscle and liver dropped in parallel or even more than plasma pH, whereas pHi in skeletal muscle changed less resulting in a delta pHi/delta pHe value of less than 0.6. Intracellular [lactate] and [Ca2+] increased considerably, but attained concentrations much smaller than those observed in the extracellular compartment. The intracellular concentrations of K+, Na+ and Mg2+ were also significantly affected, the changes, however, were small in comparison with those observed for Ca2+ and lactate concentration. The water distribution between intra- and extracellular compartments remained essentially unaffected by anoxia. It is concluded that the considerable increase in extracellular Mg2+ and Ca2+ cannot be the result of release from muscle cells and has to be attributed to release from skeleton and shell.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1983

Contribution of net ion transfer mechanisms to acid-base regulation after exhausting activity in the larger spotted dogfish (Scyliorhinus stellaris).

Specimens of the larger spotted dogfish (Scyliorhinus stellaris) were electrically stimulated to exhaustion in a closed seawater recirculation system. The production of large quantities of lactic acid by anaerobic metabolism and the resultant efflux of the dissociation products, H+ and lactate, from the white musculature resulted in severe acid-base disturbances and in increases in plasma lactate concentration, the two effects having extremely different time courses. Plasma pH and bicarbonate were maximally depressed 15-30 min after exercise, whereas peak lactate concentrations of up to 30 mM were not attained before 4-8 h after exercise. The acid-base status were restored to normal 10-14 h after exercise, long before the aerobic processing of surplus lactic acid was complete 22-30 h after exercise. This behaviour can be explained on the basis of an interaction of transfer rates, buffer values and equilibria between intracellular and extracellular compartments with the transient net transfer of surplus H+ ions to the environmental water. About half of the original quantity of H+ was transferred net to the environment via the branchial epithelium during the first 8-10 h, and it was later taken up again at the rate of aerobic lactic acid processing in the metabolism of the fish, whereas a transfer of lactate was not observed at any time during the experiment. As a result, the distribution patterns of H+ and lactate differed from each other and varied with time elapsed after anaerobic exercise, leading to the apparent 'H+ ion deficit' which has been observed in the blood of several fish species during lactacidosis. Net transfer of H+ ions to the environment facilitates rapid normalization of the acid-base status long before the original stress, lactic acid, is removed from the organism and thus represents an effective regulatory mechanism for the defence of the internal milieu in fish.

Acid-Base Equilibrium↗
PubMed1983

The mechanism of intracardiac shunting in the lizard Varanus exanthematicus.

Intracardiac shunting was studied in unanaesthetized and unrestrained specimens of Varanus exanthematicus by simultaneous injection of radioactively labelled microspheres (15 micron) into the right and left atria. Lung ventilation was monitored by intratracheal pneumotachography. It was found that intracardiac shunting was not significantly affected by the spontaneously occurring periods of ventilation and apnoea: the right-to-left shunt averaged 29 and 31%, respectively, and the left-to-right shunt was 11% in both conditions. The observed shunting, although rather constant with time and independent of the ventilatory state, varied in different individuals. Anatomical studies and intracardiac pressure measurements revealed that, in spite of crocodilian-like systolic pressure separation between pulmonary and systemic circulation (based on the muscular ridge, 'Muskelleiste', between cavum venosum and cavum pulmonale), the cavum venosum is shared by both the pulmonary and the systemic circulation. Intracardiac shunting appears to be mainly due to wash-out of the cavum venosum: blood remaining in this chamber at the end of systole (oxygenated) or at the end of diastole (deoxygenated) is washed into the respective 'inadequate' vascular bed during the next half-cycle of heart action. Thus the extent of intracardiac shunting is expected to depend primarily on the volume and the changes in volume of the cavum venosum during the cardiac cycle.

Animals↗
PubMed1983

Regulation of the acid-base status during environmental hypercapnia in the marine teleost fish Conger conger.

Specimens of Conger conger (L.) were exposed to environmental hypercapnia in a closed recirculating seawater system. Arterial plasma pH, PCO2 and bicarbonate concentration, as well as the net transfer of bicarbonate and ammonia between fish and ambient seawater, were monitored for 30 h of hypercapnia. The initial hypercapnia-induced reduction of arterial pH by about 0.4 pH units was restored to near control values within 10 h of hypercapnia by compensatory elevation of plasma bicarbonate concentration. The continuous rise in extracellular bicarbonate from about 5 to 22 mM during this time was the result of two different mechanisms. Initially, there was a net bicarbonate transfer from the intracellular space to the extracellular compartment until the net uptake of bicarbonate from the seawater started. The amount of bicarbonate originally transferred to the extracellular space was then returned to the intracellular compartment and finally the changes in both extracellular and intracellular pH were compensated by bicarbonate taken up from the environmental seawater. Since the ammonia excretion was not increased during hypercapnia and the pattern of plasma electrolyte concentrations does not favour the H+/Na+ ion exchange mechanism, it is concluded that the additional bicarbonate is gained by active HCO3-/Cl- ion exchange against the electrochemical gradient between fish and seawater.

Acid-Base Imbalance↗