Biomedical subjects

A Bidani

Publications and source records attributed to A Bidani.

At least 73 records · Page 4Linked to original sources

PubMed1994

IVOX with gradual permissive hypercapnia: a new management technique for respiratory failure.

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1994

Determinants of inhaled ozone absorption in isolated rat lungs.

Using an isolated rat lung model, we investigated the characteristics of pulmonary O3 absorption, including the contributory role of chemical reaction vs physical solubility. Due to the physicochemical similarities between O3 and NO2, we utilized investigational strategies analogous to those previously employed to characterize NO2 absorption kinetics. The effects of vascular perfusion, temperature, inspired concentration ([O3]i), surface area, and minute ventilation (tidal volume (Vt) times ventilation frequency (f)) on air space O3 clearance during quasi-steady-state exposures were investigated using fractional uptakes (%U) and reactive uptake coefficients (k') as endpoints. We found the following: (1) At 1 ppm [O3]i (37 degrees C), %U (95 +/- 5%) was perfusion independent (60 min). (2) %U displayed temperature dependence (r = 0.99). Activation energies (Ea) and Q10 were computed from Arrhenius plots (ln k' vs 1/T; r = -0.99). For 1 ppm (11-37 degrees C), Ea = 4140 kcal/g.mol and Q10 = 1.23. (3) Absorption demonstrated [O3]i dependence. At 25 degrees C, < or = 1 ppm displayed %U = 86 +/- 4% with k' = 234 ml/min. Exposures > 1 ppm resulted in decreasing %U and k' (5 ppm %U = 60 +/- 3% and k' = 121 ml/min). (4) To evaluate epithelial damage, lactate dehydrogenase (LDH) activity was quantified in cell-free bronchoalveolar lavage fluid. For exposures < or = 1 ppm LDH equaled control, while for exposures > 1 ppm LDH steadily increased to a four-fold maximum at 5 ppm. (5) O3 uptake was independent of functional residual capacity-induced changes in air space surface area. (6) Absorption was proportional to Vt (r = 0.99) and displayed notable ventilation frequency-dependent decline above 70 breaths per minute. Based on the perfusion independence, temperature dependence, and the Ea and Q10, we conclude that O3 absorption in isolated lungs involves a reactive component. While k' remained stable from 0 to 1 ppm O3, at concentrations above 1 ppm other contributory factors such as O3/substrate reaction kinetics, epithelial damage, and solute O3 backpressure may affect the overall net absorption rate. In addition, the data suggest that O3 uptake may be principally localized to the conducting airways.

Absorption↗

PubMed1994

Performance of an intravenous gas exchanger (IVOX) in a venovenous bypass circuit.

To analyze quantitatively the performance of the intravenacaval blood gas exchanger (IVOX), we developed a right atrium-pulmonary artery venovenous extracorporeal bypass circuit. Oxygen transfer and carbon dioxide removal were calculated at different blood flow rates, different hemoglobin levels, and during permissive hypercapnia. Oxygen transfer increased linearly with blood flow up to 41 mL/min. Likewise, O2 transfer increased linearly with hemoglobin levels up to 7.5 g/dL, but no further increases were achieved above this level. Carbon dioxide removal increased linearly as flow increased from 1.0 to 3.0 L/min but did not increase further for higher flows. Carbon dioxide removal was 45 mL/min at blood carbon dioxide tension of 42 mm Hg but increased to a maximum of 81 mL/min at a carbon dioxide tension of 90 mm Hg. We conclude that IVOX is a diffusion-limited device dependent on blood flow, hemoglobin content, and the gas pressure gradient across the membrane. Further engineering improvements are needed to improve the gas exchange performance of IVOX.

Animals↗

PubMed1994

Intravascular membrane oxygenation and carbon dioxide removal with IVOX: can improved design and permissive hypercapnia achieve adequate respiratory support during severe respiratory failure?

The intravenacaval oxygenator and carbon dioxide removal device (IVOX) conceived by Mortensen at CardioPulmonics is a diffusion-limited device capable of removing 30% of CO2 production of an adult at normocapnia with minimal reduction in ventilator requirements. Through mathematical modeling, an ex vivo venovenous bypass circuit to model the vena cava and animal models of severe smoke inhalation injury, the practice of permissive hypercapnia has been established to enhance CO2 removal by IVOX. By allowing the blood PCO2 to rise gradually, the CO2 excretion by IVOX can be linearly increased in a 1:1 relationship. Experimental and clinical studies have shown that CO2 removal by IVOX increased from 30-40 ml/min at normal blood PCO2 to 80-90 ml/min at PCO2 of 90 mm Hg. In addition, IVOX with permissive hypercapnia allowed a significant reduction in minute ventilation and peak airway pressure. Design changes could also improve the performance of IVOX. Increased surface area and mixing with more fibers and crimping in new prototypes of IVOX significantly increased CO2 removal and oxygen transfer. Active mixing in the blood to decrease the boundary layer resistance can further enhance gas exchange of IVOX. In conclusion, gas exchange by the current design of IVOX is limited, and improvements in design are needed for it to become a more clinically applicable device. Permissive hypercapnia can significantly enhance CO2 removal by IVOX as well as significantly reduce ventilator requirements.

Adult↗

PubMed1994

In vivo gas transfer performance of the intravascular oxygenator in acute respiratory failure.

The intravascular oxygenator (IVOX) has undergone both animal and clinical trials. Data from the animal studies have demonstrated that the device is capable of transferring up to approximately 100 ml/min of oxygen and carbon dioxide. Initial data from the human trials suggest that gas transfer, although approaching these levels, varied widely in patients with respiratory failure. We studied the factors affecting gas exchange in 26 patients with severe acute respiratory failure who underwent intravenacaval support of gas exchange with IVOX. The patients underwent monitoring of IVOX gas transfer rates, hemodynamics, blood gases, and ventilation parameters at scheduled intervals following device insertion. All devices functioned following implantation. The mean value for O2 transfer was 64 +/- 21 SD ml/min (range 15-114 ml/min) and for CO2 transfer was 48 +/- 17 ml.min-1 (range 14-112 ml/min). CO2 transfer correlated positively with device surface area, cardiac output, and mixed venous Pco2 and negatively with duration of implantation. O2 transfer did not correlate with any patient factors probably due to error inherent in the measurement of this variable. Independent measurements of IVOX gas transfer by respiratory gas exchange in a subset of patients with normal values of mixed venous Pco2 were in good agreement with the routine measurements and indicated that the device provided up to 26% of gas exchange requirements in this subset. We conclude that IVOX transfers clinically useful amounts of oxygen and carbon dioxide in vivo. Factors that influence gas transfer include device surface area, PvCO2, cardiac output, and duration of implantation. Optimization of these factors (such as with permissive hypercapnea) could result in enhanced performance in vivo.

Acute Disease↗

PubMed1994

pHi regulation in alveolar macrophages: relative roles of Na(+)-H+ antiport and H(+)-ATPase.

In rabbit alveolar macrophages, recovery of intracellular pH (pHi) from acid loads to pHi values > or = 6.8 at an extracellular pH (pHo) of 7.4 (nominal absence of CO2-HCO3-) is insensitive to amiloride, an inhibitor of Na(+)-H+ exchange, and abolished by bafilomycin A1, an inhibitor of vacuolar-type H(+)-ATPase [A. Bidani, S.E.S. Brown, T.A. Heming, R. Gurich, and T.D. Dubose, Jr. Am. J. Physiol. 257 (Cell Physiol. 26): C65-C76, 1989; A. Bidani and S. E. S. Brown. Am. J. Physiol. 259 (Cell Physiol. 28): C586-C598, 1990]. To further evaluate the roles of Na(+)-H+ exchange and H(+)-ATPase activity in pHi regulation in rabbit alveolar macrophages, we have investigated the effects of amiloride and bafilomycin over a greater range of pHi (6.3-7.0) and pHo (5.0-7.4). The results indicate that rabbit alveolar macrophages possess H(+)-ATPase and a Na(+)-H+ antiporter, both of which are activated by decrements in pHi. However, in all cases, H(+)-ATPase activity exclusively determined basal pHi and was the principal mechanism (> 50%) for pHi recovery from intracellular acid loads. The pHi set point for activation of Na(+)-H+ exchange was approximately 6.8 at pHo of 7.4 and approximately 6.5 at pHo of 6.8. Na(+)-H+ exchange did not contribute significantly to pHi recovery at acid-loaded pHi above these set points. At pHo of 7.4 and pHi > or = 6.8, pHi recovery displayed an activation energy of approximately 11,000 kcal/mol and temperature coefficient of approximately 2.1, which are consistent with an energy-dependent process (i.e., H+ pump).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1994

Roles of intra- and extracellular carbonic anhydrase in alveolar-capillary CO2 equilibration.

Alveolar-capillary CO2 equilibration involves diffusive equilibration of CO2 across the blood-gas barrier and chemical equilibration of perfusate CO2-HCO-3-H+ reactions. These processes are governed by different, but related, driving forces and conductances. The present study examined the importance of pulmonary carbonic anhydrase (CA) for diffusive and reactive CO2 equilibration in isolated rat lungs. Lungs were perfused with salines containing membrane-impermeant or -permeant inhibitors of CA. Measurements of CO2 excretion rate, equilibrated venous and arterial PCO2 and pH, and postcapillary pH and PCO2 disequilibria were used, together with our previous model of CO2-HCO-3-H+ reactions and transport in saline-perfused capillaries (Bidani et al. J. Appl. Physiol. 55: 75-83, 1983), to compute the relevant driving forces and conductances. Reactive CO2 equilibration was markedly affected by extracellular (vascular) CA activity but not by the activity of intracellular (cytosolic) CA. The driving force for CO2 diffusion was strongly influenced by vascular CA activity. The conductance for CO2 diffusion was independent of CA activity. The minimum conductance for CO2 diffusion was estimated to be 700-800 ml.min-1.Torr-1. The results indicate that extracellular vascular CA activity influences both diffusive and reactive CO2 equilibration. However, cytosolic CA has no detectable role in alveolar-capillary CO2 equilibration.

Acetazolamide↗

PubMed1994

Analysis of factors affecting gas exchange in intravascular blood gas exchanger.

A mathematical model of an intravascular hollow-fiber gas-exchange device, called IVOX, has been developed using a Krogh cylinder-like approach with a repeating unit structure comprised of a single fiber with gas flowing through its lumen surrounded by a coaxial cylinder of blood flowing in the opposite direction. Species mass balances on O2 and CO2 result in a nonlinear coupled set of convective-diffusion parabolic partial differential equations that are solved numerically using an alternating-direction implicit finite-difference method. Computed results indicated the presence of a large resistance to gas transport on the external (blood) side of the hollow-fiber exchanger. Increasing gas flow through the device favored CO2 removal from but not O2 addition to blood. Increasing blood flow over the device favored both CO2 removal as well as O2 addition. The rate of CO2 removal increased linearly with the transmural PCO2 gradient imposed across the device. The effect of fiber crimping on blood phase mass transfer resistance was evaluated indirectly by varying species blood diffusivity. Computed results indicated that CO2 excretion by IVOX can be significantly enhanced with improved bulk mixing of vena caval blood around the IVOX fibers.

Blood Gas Analysis↗

PubMed1993

Reversible compensatory hypertrophy in rat kidneys: morphometric characterization.

Functional renal compensatory hypertrophy (RCH) in the uninephrectomized rat is completely reversible by transplantation in Brown Norway (BN) rats, while anatomic RCH is not. To determine the nephron element(s) responsible for persistent anatomic RCH, we performed morphometric analysis on perfusion fixed rat kidneys following renal function studies. In this model the function of renal transplants is not different from contralateral and unmanipulated control kidneys, and there is no histological evidence of rejection. Rats uninephrectomized for three or six weeks had larger glomeruli than controls, and after transplantation of a previously hypertrophied kidney into a rat with a normal or a solitary hypertrophied kidney, glomerular size returned to control levels. Increased glomerular capillary volume (CVCP) in kidneys with RCH was due to increased capillary length (LCP; 13.1 +/- 1.0 mm cf. 10.3 +/- 0.9, P < 0.01) without increase in capillary radius (RCP; 3.26 +/- 0.33 microM cf. 3.28 +/- 0.24). In contrast, return of CVCP to control levels in kidneys undergoing regression was associated with persistently elevated LCP (13.0 +2- 2.9 mm; native previously hypertrophied kidney; 12.2 +/- 0.9; transplanted previously hypertrophied kidney vs. 10.3 +/- 0.9, P < 0.01) and decreased RCP (2.79 +/- 0.10 microM and 2.73 +/- 0.09, cf 3.28 +/- 0.24, P < 0.01). RCH was associated with proportional increases in glomerular, tubular, and vascular-interstitial volumes while only elevated tubular volume persisted during regression. Altered glomerular capillary dimensions and increased tubular volumes acquired during renal RCH induced by unilateral nephrectomy persisted during complete functional regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Streptozotocin-induced renal hemodynamic changes in isogenic Lewis rats: a kidney transplant study.

Streptozotocin (STZ)-induced diabetes mellitus is associated with decreased renal clearances of inulin and p-aminohippurate (PAH). The present experiments were designed to determine whether STZ-induced renal hemodynamic changes are due to the drug per se, rather than to the diabetic state that it induces. Isogenic Lewis rats with native right and transplanted left kidneys were studied. In one group, kidney donors received 50 mg STZ/kg body wt on day 1 and transplantation was performed on day 4 (untreated recipients). On day 29, the inulin and PAH clearances of these nondiabetic recipients were, respectively, 0.94 +/- 0.04 and 2.58 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (previously exposed to STZ) and 0.95 +/- 0.07 and 2.54 +/- 0.14 ml.min-1 x g-1 for the native right kidney (never exposed to STZ). In another group, recipients received STZ on day 1 and transplantation was performed on day 4 (untreated donors). On day 29, the inulin and PAH clearances of these diabetic recipients were, respectively, 0.62 +/- 0.04 and 1.46 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (never exposed to STZ) and 0.61 +/- 0.05 and 1.42 +/- 0.08 ml.min-1 x g-1 for the native right kidney (previously exposed to STZ). We conclude that the diabetic state, rather than STZ, is responsible for the decreased renal clearances of inulin and PAH in this experimental model.

Animals↗

PubMed1993

Inhibitor sensitivity of pulmonary vascular carbonic anhydrase.

The inhibitor sensitivity of pulmonary vascular carbonic anhydrase (CA) was examined in situ to identify the specific isozyme responsible for vascular activity and to study its distribution in the lung. Vascular CA activity was monitored in isolated rat lungs by measuring the rate of CO2 excretion and the magnitude of postcapillary CO2-HCO(3-)-H+ disequilibria. Lungs were perfused with isotonic salines containing gluconate, sulfate, Cl-, or I-, with or without sulfonamide derivatives. Effects of a CA inhibitor purified from porcine blood plasma were also determined. Vascular CA activity was unaffected by gluconate, sulfate, Cl-, and I- (< or = 100 mM). Sulfonamides with vastly different rates of membrane permeation (i.e., readily permeating ethoxzolamide, slowly permeating acetazolamide, and membrane-impermeant quaternary ammonium sulfanilamide) were capable of accessing all vascular CA with similar rates of access. The porcine inhibitor of CA (340 nM) produced a significant, but submaximal, inhibition of vascular CA activity. The data suggest that pulmonary vascular activity reflects a high-activity membrane-bound isozyme, CA IV, which is located on the extracellular luminal surface of capillary endothelial cells.

Animals↗

PubMed1992

Intravascular membrane oxygenation and carbon dioxide removal--a new application for permissive hypercapnia?

Pressure limited ventilation or "lung rest" may prevent further exacerbation of acute lung injury from high airway pressures. A therapeutic goal of an intracorporeal oxygenation and carbon dioxide removal device (IVOX) is reduction of airway pressures. We noted increased IVOX CO2 removal as mixed venous CO2 increased in experimental animals. However, we recognize the limited clinical utility of removing approximately 30% of venous CO2. Therefore, intentional hypoventilation to limit airway pressures (mild permissive hypercapnia) was used in 5 patients with respiratory failure, and again we noted improved CO2 removal with increasing mixed venous CO2 concentrations. Preliminary calculations demonstrate that a CO2 gradient of approximately 70 mm Hg is needed to remove 100 ml CO2/min. The use of more aggressive permissive hypercapnia protocols with IVOX may permit further reduction in airway pressure without problems of severe respiratory acidosis.

Adolescent↗

PubMed1992

Influence of proton availability on intracapillary CO2-HCO3(-)-H+ reactions in isolated rat lungs.

Transcapillary CO2 exchange entails a transient perfusate CO2-HCO3(-)-H+ disequilibrium, leading to net loading or unloading of blood HCO3-. Perfusate reequilibration may or may not reach completion during the time of capillary transit, depending on the rate of intracapillary CO2-HCO3(-)-H+ reactions. Failure to reestablish equilibrium within the "open" capillary system leads to continued reequilibration in the "closed" postcapillary vasculature with resultant shifts in postcapillary perfusate PCO2, pH, and [HCO3-]. In the present study, we determined the effects of perfusate nonbicarbonate buffer capacity (beta) on intracapillary CO2-HCO3(-)-H+ reactions in isolated saline-perfused rat lungs. Effects of beta on the rate of transcapillary CO2 excretion (VCO2) and the magnitude of the postcapillary perfusate pH disequilibrium were measured as a function of luminal vascular carbonic anhydrase (CA) activity. The data indicate that beta markedly influenced the kinetics and dynamics of intravascular CO2-HCO3(-)-H+ reactions. beta affected VCO2 and the relative enhancement of VCO2 by luminal vascular CA. The data emphasize the inadequacies of using traditional "equilibrium" models of the CO2-HCO3(-)-H+ system to investigate capillary CO2 transport and exchange, even in organs (e.g., lungs) that contain significant luminal vascular CA activity.

Animals↗

PubMed1992

Kinetics of NO2 air space absorption in isolated rat lungs.

We previously showed, during quasi-steady-state exposures, that the rate of inhaled NO2 uptake displays reaction-mediated characteristics (J. Appl. Physiol. 68: 594-603, 1990). In vitro kinetic studies of pulmonary epithelial lining fluid (ELF) demonstrated that NO2 interfacial transfer into ELF exhibits first-order kinetics with respect to NO2, attains [NO2]-dependent rate saturation, and is aqueous substrate dependent (J. Appl. Physiol. 71: 1502-1510, 1991). We have extended these observations by evaluating the kinetics of NO2 gas phase disappearance in isolated ventilating rat lungs. Transient exposures (2-3/lung at 25 degrees C) employed rebreathing (NO2-air) from a non-compliant continuously stirred closed chamber. We observed that 1) NO2 uptake rate is independent of exposure period, 2) NO2 gas phase disappearance exhibited first-order kinetics [initial rate (r*) saturation occurred when [NO2] > 11 ppm], 3) the mean effective rate constant (k*) for NO2 gas phase disappearance ([NO2] < or = 11 ppm, tidal volume = 2.3 ml, functional residual capacity = 4 ml, ventilation frequency = 50/min) was 83 +/- 5 ml/min, 4) with [NO2] < or = 11 ppm, k* and r* were proportional to tidal volume, and 5) NO2 fractional uptakes were constant across [NO2] (< or = 11 ppm) and tidal volumes but exceeded quasi-steady-state observations. Preliminary data indicate that this divergence may be related to the inspired PCO2. These results suggest that NO2 reactive uptake within rebreathing isolated lungs follows first-order kinetics and displays initial rate saturation, similar to isolated ELF.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1992

The effect of hyperoxic exposure on antioxidant enzyme activities of alveolar type II cells in neonatal and adult rats.

Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type II cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type II cells compared with adults. Baseline enzyme activities did not differ in neonatal type II cells and lung homogenates except for lower catalase activity in type II cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type II cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type II cells there was a significant decrease in SOD activity after O2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type II cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type II cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type II cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate.

Animals↗

PubMed1991

High osmolality-low pH flush solutions improve renal transplant function in rats.

Although transplanting rat kidneys is an established microsurgical technique, inulin clearance is abnormally low, due to rejection and/or warm ischemia-induced damage. In the present studies, rejection was avoided by using inbred Brown Norway rats as donors and recipients. Donor kidneys were flushed with ice-cold solutions of various composition (saline, saline + 200 or 400 mM mannitol) and pHs (5.7, 6.4, and 7.4), and the kidneys were kept cold during transplantation into unilaterally nephrectomized recipients. Renal function was assessed by clearance techniques 1 week later. In control rats, with both native kidneys intact, the ratio of inulin clearance, left kidney to right kidney, was 0.99 +/- 0.02. In rats with a native right kidney and a transplanted left kidney that had been flushed with saline, the ratio was considerably lower (0.46 +/- 0.09). Adding 200 mM mannitol to the saline flush solution increased the ratio (0.89 +/- 0.09). In comparison, adding 200 mM mannitol and 5 mM phosphate buffer at pH 7.4 resulted in a somewhat lower ratio (0.80 +/- 0.09), whereas adding 200 mM mannitol and 5 mM phosphate buffer at pH 5.7 resulted in a higher ratio, one that was indistinguishable from control (0.97 +/- 0.09). Thus, in this latter group, the inulin clearances of the transplanted kidneys were identical to those of the contralateral native kidneys.

Animals↗

PubMed1991

Transfer of NO2 through pulmonary epithelial lining fluid.

Absorption of inhaled NO2 across the pulmonary gas/tissue interface is principally governed by chemical reaction(s) rather than by physical solubility. While the kinetics of NO2 transfer into reactant-containing aqueous solutions appear to be bulk phase independent, it is unclear whether unreacted NO2 diffuses appreciably through the epithelial lining fluid (ELF) to cellular compartments. We avoided the difficulties associated with directly quantifying NO2 dissolved in biological fluids by indirectly determining the potential for NO2 penetration to underlying tissues. An in vitro system was developed which horizontally suspended a wettable, gas permeable, fibrous material between two gas chambers. Aqueous substrates were applied to the sieve material and NO2 (10.9 ppm) was introduced into one chamber and sampled for in the other. O2 served as a tracer gas. We determined the influence of ELF, a model biochemical (reduced glutathione; GSH), and PO4 buffer (control) on NO2 transfer as evaluated by "breakthrough time." (A) Both O2 and NO2 rapidly diffused through the sieve material when dry. Under PO4 wetted conditions, O2 continued to penetrate rapidly but NO2 transfer was slightly inhibited relative to O2. (B) Addition of GSH (1 mM) significantly prolonged NO2 breakthrough time. Increasing initial [GSH] resulted in concomitant prolongation of NO2 breakthrough time. (C) We observed a direct correlation between oxidation of sieve GSH and NO2 breakthrough. (D) Freshly harvested rat ELF inhibited NO2 transfer in a concentration-dependent manner similar to GSH. These data suggest that in the presence of reactant solutes, unreacted NO2 does not penetrate through the ELF layer. Reactive absorption must, therefore, occur primarily within the ELF compartment so that reaction products which induce subsequent toxicity are generated as a result of the initial uptake interactions.

Animals↗

PubMed1991

Reversible compensatory hypertrophy in transplanted brown Norway rat kidneys.

Recently we described methods for optimizing the function of transplanted rat kidneys. In unilaterally nephrectomized recipients, one week after surgery, the left transplanted kidney was identical to the right native kidney with respect to wet weight and the clearances of inulin and para-aminohippuric acid (PAH). The goals of the present experiments were first, to extend the post-surgery period to three weeks (sufficient to allow hypertrophic changes), and second, to study function of transplanted hypertrophied kidneys. Genetically identical Brown Norway rats were used as donor and recipients. Three weeks after transplanting a normal kidney into a unilaterally-nephrectomized recipient, the transplanted kidney had a normal plasma flow and was identical to the contralateral native kidney with respect to wet weight and the clearances of inulin and PAH. Three weeks after transplanting a normal kidney into a bilaterally-nephrectomized recipient, the wet weight, inulin and PAH clearances, and plasma flow of the transplanted kidney were all higher than control, and not significantly different from those observed in unilaterally-nephrectomized control rats. Thus, transplanted and native kidneys exhibited the same degree of compensatory hypertrophy. Hypertrophied donor kidneys (that is, the donor rat had been unilaterally-nephrectomized three weeks previously) remained hypertrophied in bilaterally-nephrectomized recipients, but in unilaterally-nephrectomized recipients, they regressed towards normal (that is, the values of wet weight, inulin and PAH clearances and plasma flow were significantly less than those in rats with only one kidney) while the contralateral native kidney remained normal (values of wet weight and inulin and PAH clearances were not different from control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗