Errors in estimating lung liquid volume in fetal lambs when using radiolabeled serum albumin and blue dextran.

Fetal lung liquid volume is usually determined by using radio-iodinated serum albumin (RISA) or blue dextran (BD) as volume tracers. We tested the reliability of both tracers at 124 (G124) and 142 days of gestation (G142; term = G147) when the labels were employed simultaneously. We measured the proportion of label bound reversibly to the lung, or apparently lost from the lung compartment, by washing out the lung with saline and 5% albumin. At G124, volume estimates with the two labels were similar. At G142, the volume estimate with BD (36.3 +/- 8.7 ml/kg of body wt) was higher (P < 0. 05) than with RISA (22.3 +/- 3.5 ml/kg). This difference resulted from reversible binding of BD, because 5% albumin washout released 38.5 +/- 4.0% of the BD added at the start of the experiment but a lesser amount of RISA (9.8 +/- 0.7%; P < 0.05). At G142, when RISA was used alone, its reversible binding was 1.3 +/- 0.2%. Background absorbance increased during experiments, giving rise to an apparent increase in BD concentration. We conclude that RISA is an effective tracer for lung liquid volume determination in the fetal lamb, whereas our findings of substantial epithelial binding of BD and large changes in background absorbance demonstrate that, under the conditions of our experiments, BD is a poor tracer close to term.     

The effects of temperature change on lung liquid production by in vitro lungs from fetal guinea pigs

Lungs from fetal guinea pigs of 58-65 days of gestation were supported in vitro for 3 h, and lung liquid production rates were measured by a dye dilution technique. In 36 control preparations, incubated continuously at 37 degrees C, the average production rate in the first hour was 1.46 +/- 0.23 ml/h per kg body weight; there was no significant change over the following two h. In 36 further preparations the temperature was changed during the middle hour (ABA), with the following % reductions in production rates: at -1 degrees C (relative to 37 degrees C), 68.2 +/- 17.1%; -2 degrees C, 125.5 +/- 30.1% (reabsorption); -3 degrees C, 103.8 +/- 32.8% (reabsorption); -5 degrees C, 82.7 +/- 16.6%, -8 degrees C, 94.7 +/- 1.8 %; +2 degrees C, 100.7 +/- 12.6% (all significant, P less than 0.025-0.005). Slow recoveries followed a return to starting conditions, except after the increase in temperature, 10(-6) M amiloride abolished reabsorption, but not depression, during the maximal effects of temperature reduction (at -2 degrees C, n = 6); amiloride had no effect on control preparations (n = 6). These results suggest that: (a) reductions of 2-3 degrees C, as seen in the delivery room, abolish secretion, but not reabsorption of lung fluid; larger reductions stop both processes; (b) the reabsorptions seen after a fall in temperature depend on Na(+)-transport mechanisms; (c) lung liquid production was sensitive to a rise in temperature, so that fevers might adversely affect lung development, and (d) the fall in temperature at birth may be an important factor in the early reabsorption of lung liquid.     

Fluid production by in vitro lungs from fetal guinea pigs

Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10(-4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung.     

Effects of norepinephrine on lung liquid production by in vitro lungs from fetal guinea pigs

Lungs from near-term fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Untreated control preparations produced fluid at 1.38 +/- 0.30 mL x kg(-1) body weight x h(-1), with no significant change (ANOVA; regression analysis); those given 1.24 x 10(-9) or 1.24 x 10(-8) M norepinephrine during the middle hour showed no significant change, but those given concentrations between 5.24 x 10(-8) and 1.24 x 10(-5) M all showed significant reductions or fluid reabsorption (based on 42 fetuses). The responses showed a linear relationship with the log concentration (r = 0.97). They appeared to involve alpha-adrenoreceptors, since responses to 10(-7) M norepinephrine were unaffected by 10(-6) M propranolol, but those to 10(-7) and 1.24 x 10(-6) M norepinephrine were abolished by 10(-6) and 1.78 x 10(-5) M phentolamine, respectively (based on 48 fetuses). Activation was through alpha2-adrenoreceptors, since responses to 10(-7) and 10(-5) M norepinephrine were abolished by 10(-4) M yohimbine, but not by 10(-5) M prazosin (based on 60 fetuses). The results show that norepinephrine is able to reduce lung liquid production when at plasma levels present at birth, and that it can produce reabsorption; unlike epinephrine, there was no reduction in responses at high concentrations. This work reintroduces a neglected factor, norepinephrine, into possible controls of lung liquid reabsorption, and opens up the potential for neural controls.     

Adverse events after infusions of cryopreserved hematopoietic stem cells depend on non-mononuclear cells in the infused suspension and patient age

BACKGROUND: Adverse events (AE) represent a significant clinical problem after infusion of cryopreserved HPC. However, the factors playing a role in the pathogenesis have not yet been fully established. METHODS: We prospectively collected data on AE that occurred with 179 HPC infusions performed on patients affected with hematologic neoplasm after high-dose chemotherapy. The stem cell source was hemopoietic progenitor cells aphaeresis (HPC-A) in 157 cases and hemopoietic progenitor cell BM (HPC-BM) in 22 cases. In all cases, an endotoxin-free DMSO was used. RESULTS: One or more AE were registered in 51/179 infusions (28.6%). The frequency of AE was higher after HPC-A than after HPC-BM (31.3% vs. 4.5%; chi(2) test, P =0.008). With univariate logistic regression, other factors found important for AE were age (P =0.028), number of total nucleated cells infused per kilogram (P =0.002), volume per kilogram infused (P =0.057), volume of packed RBC (P =0.019), a content of non-mononuclear cells >0.5 x 10(8)/kg (

0.5 x 10(8)/kg (P =0.0003) remained significant. A significant correlation existed between reduction of cardiac frequency both with volume per kilogram infused (r =0.221, P =0.02) and actual time of infusion (r =0.269, P =0.005). DISCUSSION: Cardiovascular changes are influenced by volume per kilogram infused and by actual time of infusion, while non-cardiovascular AE are dependent on patient age and contamination by non-mononuclear cells in apheretic harvests.     

Technique-dependent variations in cerebral microvessel blood volumes and hematocrits in the rat.

To quantitate small parenchymal microvessel blood volumes in the brain, the distribution spaces of radiolabeled red blood cells (RBC) and serum albumin (RISA) were assessed in rats by different methods of tissue sampling and radioassay. Three minutes after intravenous administration of 55Fe-RBCs and/or 125I-RISA, the rats were decapitated. The brain was either immediately frozen within the skull and later removed (head-frozen group) or rapidly removed from the skull and then frozen (brain-frozen group). Radioactivity was measured either by liquid scintillation counting of tissue pieces, which contained pial plus large and small parenchymal microvessels, or by quantitative autoradiography (QAR) of tissue sections, which indicated small parenchymal microvessel blood only. In 12 of 15 areas, the RISA, RBC, and blood volumes determined by liquid scintillation counting of head-frozen tissue pieces were equal to or greater than those of brain-frozen tissue; this indicated less than or equal to 25% greater blood retention in pial and parenchymal microvessels with head freezing. At the parenchymal microvessel level (QAR assay), the distribution volumes of RBCs, RISA, and blood were similar with the two freezing techniques; hence with QAR either freezing procedure can be used to assess small parenchymal microvessel blood volumes.     

The effects of low fat chocolate milk on postexercise recovery in collegiate athletes

Spaccarotella, KJ and Andzel, WD. The effects of low fat chocolate milk on postexercise recovery in collegiate athletes. J Strength Cond Res 25(12): 3456-3460, 2011-Drinking chocolate milk between exercise sessions may improve recovery. The purpose of this study was to examine the effects of low fat chocolate milk vs. a carbohydrate-electrolyte beverage (CE) on recovery between preseason practice sessions among 5 male and 8 female Division III soccer players. The study used a randomized crossover design: between morning and afternoon practices, athletes received either an amount of chocolate milk that provided 1 g carbohydrate per kilogram body weight or an equal volume of CE (mean volume of 615 ± 101 ml). After their afternoon practice, they completed a shuttle run to fatigue. Data were analyzed using the Wilcoxon paired rank-sign test (for shuttle run time) and the paired samples t-test (for dietary intake). No significant differences in run time were reported for the group. For the men only, there was a trend of increased time to fatigue with chocolate milk compared with the CE (exact p = 0.03). Low fat chocolate milk may therefore be as good as a CE at promoting recovery between training sessions during preseason.     

The combined effects of protein intake and resistance training on serum osteocalcin concentrations in strength and power athletes

The purpose of the present investigation was to examine the combined effects of protein intake and resistance training on a blood marker of bone osteogenesis, serum osteocalcin, in Division III football players. Thirty-three resistance-trained football players (age = 20.4 +/- 1.8 years; height = 180.9 +/- 7.0 cm; body mass = 97.2 +/- 12.6 kg) were evaluated on their protein intake and subsequently underwent 10 weeks of periodized heavy resistance training during the off season. Subjects were then placed into 1 of the following 3 groups based on relative protein intake and were instructed to maintain their diets throughout the experimental period: (a) low protein intake (<1.2 g per kilogram of body mass), (b) moderate protein intake (1.21 to 1.90 g per kilogram of body mass), or (c) high protein intake (>1.91 g per kilogram of body mass). Blood sampling occurred prior to and following the 10-week resistance training period to determine resting serum osteocalcin concentrations. A significant main effect was observed following training such that only the group who consumed <1.2 g per kilogram of body mass of protein shown significant elevations in serum osteocalcin in response to resistance training (26.8 +/- 6.4 to 33.4 +/- 6.6 ng.ml(-1)). In addition, absolute protein intake was significantly correlated to serum osteocalcin concentrations (r = 0.39). The results of the present investigation demonstrated relationships between protein intake and serum osteocalcin concentrations. In addition, the osteocalcin response to short-term resistance training appeared to be affected by protein intake.     

Growth and development of the term and premature pig-tailed macaque (Macaca nemestrina): Cardiovascular and respiratory changes during the first 3 weeks of life

Growth and development of the infant pigtailed macaque (Macaca nemestrina) over the first 3 weeks of life have been characterized by the variables of body weight, blood pressure, heart rate, ventilation, blood gas tensions, and lung mechanics. The effects of prematurity on postnatal developmental trends were assessed at gestational ages of 135–145 days (0.80 of term) and 150–155 days (0.91 of term). There was no indication that cesarean section, restraint, or instrumentation had any significant influence on the measurements. Gestational age at delivery had no effect on the minute ventilation per kilogram body weight, the hematocrit, or the heart rate; however, body weight, tidal volume, respiratory frequency, arterial gas tensions, blood pressure, and lung compliance did vary with gestational age at delivery. Postnatal maturational changes in these variables were similar between term and premature animals. The data for infant macaques and newborn humans were compared. The newborn macaque appears to be an excellent model of human developmental trends (and/or disease state) over the first 3 weeks of life, though some potentially important differences have been found.     

Extrahpetic distribution of sulfobromophthalein.

Plasma clearance of sulfobromophthalein (BSP) is widely used as a measure of hepatic function. Its validity depends upon its exclusive elimination from the body via bile. For example, in the present study, when BSP was administered intravenously (i.v.) to rats at four different doses (18.75, 37.5, 75, and 150 mg/kg), less than 0.5% of each dose was excreted into the urine and between 70 and 85% was excreted into the bile within 6 h after administration. It has been assumed that the distribution of BSP is limited to the blood and liver witith very little appearing in other tissues. When we measured the amount of BSP in the plasma, liver, and the bile 10 min after the i.v. administration of either a high (150 mg/kg) or a low (18.75 mg/kg) dose of BSP, only 60% of the dose was accounted for. The concentration of BSP and 12-I-labelled albumin (RISA) was measured in various tissue samples 10 min after administration of 17.5 or 150 mg of BSP or RISA per kilogram. More BSP was found in all tissues than was contained in the plasma entrapped therein. Thus, the distribution of BSP is not limited to the liver and plasma. During excretion BSP leaves other tissue (kidney, spleen, lung, etc.) and is ultimately excreted into the bile.     

Partial forced expiratory flow-volume curves in young children during ketamine anesthesia

Maximal flows at functional residual capacity (VmaxFRC) from partial forced expiratory flow-volume (PEFV) curves were obtained in 14 normal preschool children (8 boys, 6 girls) of average age 44 mo, under general anesthesia before elective surgery. PEFV curves were generated from end inspiration by rapid compression of the chest wall with an inflatable jacket. VmaxFRC, expressed in milliliter per second, correlated linearly with height, weight, age, and FRC in milliliter and milliliters per kilogram. The best correlation of VmaxFRC (ml/s) was to height to the power of 2.47, which agrees with the results predicted by wave-speed theory. Mean FRC-corrected VmaxFRC was 2.42 +/- 0.50 (SD) FRC's/s with no significant difference between boys (2.35 FRC's/s) and girls (2.51 FRC's/s). There was no correlation between lung-size corrected VmaxFRC and height, weight, or age, but it tended to decrease with increasing FRC. The intersubject variability for VmaxFRC was reduced by normalizing for FRC, and was significantly better than that reported for awake children. This can be attributed to the greater control over volume history and more reliable maximal flow generation during anesthesia. The intrasubject coefficient of variation (CV) for VmaxFRC was 12.2%, and the intersubject CV was 20.0%. The difference may represent the variability due to dysanapsis. It is concluded that dysanapsis is not a prominent factor in children of this age group. In addition, the similarity of the regression equation for VmaxFRC vs. height to that of FRC vs. height supports the concept of equidimensional growth of the airways and lung parenchyma.     

The rate of production of lung liquid in fetal goats, and the effect of expansion of the lungs

Fetal goats (95-155 days of gestation), delivered by Caesarian section, under chloralose (50 mg/kg), with intact umbilical cords, were monitored for lung fluid production by an impermeant tracer method. The average rate of production was 13.4 +/- 2.3 ml/h, or 6.0 +/- 0.9 ml/h per kg. Production rose exponentially towards birth, by both parameters, significant P less than 0.0001 (ml/h), or P less than 0.0005 (ml/h per kg). This indicated an increase in lung liquid production due to both growth and increased activity of the tissues. However, considerable individual variability, even between twins, suggested that this general pattern was modulated by physiological requirements. In 14 fetuses (plus 12 controls), expansion of the lungs with volumes of saline similar to those of the first inspirations (saline, 15-40 ml, matched to the optical density of the lung fluid; inspiration by spirometer, 20-25 ml), caused reduction of secretion or reabsorption of fluid. Secretion changed to reabsorption at about 50% expansion, and the probable physiological limit was estimated at 62-68% expansion. The logarithm of the % fall in production was linearly related to the % expansion (r = 0.88; P less than 0.0001); therefore, small expansions (equivalent to intrauterine breathing) would have little effect, but larger changes such as first breaths, would produce rapidly escalating effects. Controls showed no similar activity. Changes in Na+ and Cl- ions are in parallel to those of water. However, K+ ions moved into the lungs after expansion, in the opposite direction to Na+ ions, and against their concentration gradient. It is suggested that expansion of the lungs activates a Na+/K+ ATP-ase pump to aid reabsorption of salt and water at birth.     

Intravascular and extracellular volumes in the diabetic rat

Simultaneously measured intravascular (IVV) and extracellular (ECV) volumes in diabetic rats have not been reported. We evaluated IVV and ECV in alloxan induced diabetic rats which were either untreated (DU) or received supplemental daily insulin (DI) for three months. Two separate groups of control rats were comparably weight matched to each experimental group. Radio-iodinated (125-I) human serum albumin (RISA) and 35-S sulfate were used to determine IVV and ECV respectively. In DU rats, values for IVV and ECV expressed as a percentage of body weight were 9.3±0.5% and 35±2% respectively; both are significantly larger than the volumes measured in control rats (IVV=6.6±0.2%, p^<0.001 and ECV=28±1%, p<0.01). DI rats had volumes (IVV=6.0±0.3% and ECV=24±3%) which were not significantly different than those of control rats (IVV=5.7±0.1% and ECV=22±1%). Thus, untreated diabetic rats had increased IVV and ECV while diabetic rats that received insulin were normovolemic despite the presence of hyperglycemia.     

Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males

Although plasma norepinephrine (NE) increases with age in response to a variety of submaximal adrenergic stimuli, the effect of age on plasma catecholamine levels during maximal aerobic effort and during submaximal work at a fixed percent of peak O2 consumption (VO2) is unknown. We therefore measured NE, epinephrine (E), and VO2 at rest and during graded maximal treadmill exercise in 24 healthy male volunteers (ages 22-77 yr) from the Baltimore Longitudinal Study of Aging who were rigorously screened to exclude the presence of cardiovascular disease. At rest neither heart rate (HR) nor VO2 were age related. Resting NE (pg/ml) was not age related, but resting E (pg/ml) was higher in male subjects 68-77 yr old (group III) than in those aged 22-37 (group I) or 44-55 yr (group II), P less than 0.01. Maximal HR (beats/min) showed a strong inverse relationship to age (203.5 - 0.65 age, r = -0.80, P less than 0.001). Peak VO2 in milliliters per kilogram total body weight per minute decreased with age (47.7 - 0.23 age, r = -0.71, P less than 0.001). At maximal effort both NE (P less than 0.01) and E (P less than 0.05) were higher in group III than in either of the younger groups. At submaximal work levels NE and E also increased with age, and when normalized for relative effort at loads between 45 and 80% of peak VO2 both NE and E were higher in the group III male subjects, although statistical significance was reached for NE (P less than 0.01) but not for E (P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise training enhances leg vasodilatory capacity of 65-yr-old men and women

To determine whether extremity vasodilatory capacity may be augmented in older persons by endurance exercise training, lower leg blood flow and conductance were characterized plethysmographically at rest and during maximal hyperemia in 9 men and 10 women aged 64 +/- 3 (SD) yr before and after 31 +/- 6 wk of walking and jogging at 70-90% of maximal oxygen uptake for 45 min 3-5 days/wk. Maximal oxygen uptake expressed as milliliters per kilogram per minute improved 25% in men and 21% in women (P less than 0.01). Maximal leg blood flow and conductance increased in all nine men by an average of 39 +/- 33 (P less than 0.001) and 42 +/- 44% (P less than 0.004), respectively. Results were more variable in women and achieved unequivocal statistical significance only for maximal blood flow (+33 +/- 54% for blood flow and +29 +/- 55% for conductance; P less than 0.02 and P = 0.05, respectively). Body weight and skinfold adiposity declined in both sexes (P less than 0.05). Enhancement of vasodilatory capacity was related to weight loss in men and adipose tissue loss in women (r = 0.61 and 0.51, respectively; P less than 0.05). There were no significant changes in exercise capacity, body weight, or maximal blood flow in four male and three female controls aged 66 +/- 4 yr. Thus adaptability of the lower limb circulation to endurance exercise training is retained to at least age 65 yr.     

Validity of VO(2 max) in predicting blood volume: implications for the effect of fitness on aging

A multiple regression model was constructed to investigate the premise that blood volume (BV) could be predicted using several anthropometric variables, age, and maximal oxygen uptake (VO(2 max)). To test this hypothesis, age, calculated body surface area (height/weight composite), percent body fat (hydrostatic weight), and VO(2 max) were regressed on to BV using data obtained from 66 normal healthy men. Results from the evaluation of the full model indicated that the most parsimonious result was obtained when age and VO(2 max) were regressed on BV expressed per kilogram body weight. The full model accounted for 52% of the total variance in BV per kilogram body weight. Both age and VO(2 max) were related to BV in the positive direction. Percent body fat contributed <1% to the explained variance in BV when expressed in absolute BV (ml) or as BV per kilogram body weight. When the model was cross validated on 41 new subjects and BV per kilogram body weight was reexpressed as raw BV, the results indicated that the statistical model would be stable under cross validation (e.g., predictive applications) with an accuracy of +/- 1,200 ml at 95% confidence. Our results support the hypothesis that BV is an increasing function of aerobic fitness and to a lesser extent the age of the subject. The results may have implication as to a mechanism by which aerobic fitness and activity may be protective against reduced BV associated with aging.     

The effects of furosemide and bumetanide on lung liquid production by in vitro lungs from fetal guinea pigs

Lungs from fetal guinea pigs of 61 +/- 3 days of gestation were supported in vitro for 3 h, and lung liquid secretion rates were measured by a dye dilution technique based on Blue Dextran 2000. Ten preparations that had received no treatment showed an average secretion rate of 1.12 +/- 0.28 mL.kg-1 body weight.h-1 during the first hour, and there were no significant changes over the following 2 h. In studies of 54 fetal lungs, furosemide, bumetanide, control ethanol carrier, or saline alone were placed in the supporting medium during the middle hour of the 3-h incubations (ABA design). Furosemide at 10(-3) M reduced secretion 83.4 +/- 16.8%; at 10(-4) and 10(-5) M it produced smaller reductions. Bumetanide at 10(-3) M usually produced reabsorption (129.9 +/- 23.0% reduction), at 10(-4) M it reduced secretion 30.9 +/- 11.8%, but at 10(-5) M it was ineffective. Control carrier and saline were without effect. The ability of the loop diuretics to produce reabsorption of fluid in some preparations suggests the unmasking of an active reabsorptive process. The results also suggest that lung liquid secretion in the fetal guinea pig, as in the sheep, is dependent on a Na+ and Cl- cotransport system.     

Peak oxygen uptake during arm cranking for men and women

To determine upper body peak O2 uptake (VO2) in a group of young females and to obtain information on possible sex differences, 40 subjects, 20 females and 20 males, mean age 26 +/- 4 (SD) and 31 +/- 6 yr, respectively, were studied during maximal arm-cranking exercise. Peak values for power output, VO2, minute ventilation (VE), and heart rate (HR) were determined for each subject. In addition, arm-shoulder volume (A-SV) was measured before exercise. Significant differences between males and females (P less than 0.05) were found for peak power output (134 +/- 18 vs. 86 +/- 13 W), peak VO2 expressed in liters per minute (2.55 +/- 0.45 vs. 1.81 +/- 0.36) and milliliters per kilogram per minute (34.2 +/- 5.3 vs. 29.2 +/- 4.9), peak VE (95.4 +/- 14.5 vs. 70.1 +/- 19.2 1 X min-1), and A-SV (3,126 +/- 550 vs. 2,234 +/- 349 ml), whereas peak HR was not significantly different between the two groups (174 +/- 14 vs. 174 +/- 36 beats X min-1). However, when peak VO2 was corrected for arm and shoulder size there was no significant difference between the groups (0.82 +/- 0.13 vs. 0.78 +/- 0.13 ml X ml A-SV-1 X min-1). These results suggest that the observed differences between men and women for peak VO2 elicited during arm cranking when expressed in traditional terms (1 X min-1 and ml X kg-1 X min-1) are a function of the size of the contracting muscle mass and are not due to sex-related differences in either O2 delivery or the O2 utilization capacity of the muscle itself.     

Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity

Syrian Golden hamsters develop severe emphysema after a single intratracheal dose of elastase, whereas Sprague-Dawley rats exhibit mild emphysema with the same dose per kilogram body weight. We hypothesized that the development of severe emphysema is prevented in rats by the high serum level of alpha1-antitrypsin reported in rats, compared with hamsters, which provides for a high lung elastase inhibitory capacity (EIC). To explore this possibility, we challenged the antiprotease system of the rats by treating them with three similar weekly doses of elastase. Four months after treatment, we evaluated changes in histology, volume, and elastic properties of rat lungs and compared them with those of hamsters receiving a single dose of elastase. We also measured serum alpha1-antitrypsin levels and serum and lung EIC in control rats and hamsters. Results showed that, in association with 40% less serum and lung EIC compared with rats (P < 0.001), hamster lungs had upper-lobe bullae formation, severe microscopic emphysema, a fourfold increase in lung volume (P < 0.01) and a threefold increase in constant k, an index of compliance, of the lung deflation pressure-volume curve (P < 0.01). In contrast, rats developed mild emphysema, with only 50% increase in volume (P < 0.05) and 60% increase in constant k (P < 0.01). In conclusion, two species that differ in serum and lung EIC exhibit significant differences in emphysema development after elastase. Rats with high EIC, despite receiving three doses of elastase, showed significantly less derangement of morphological and physiological parameters than hamsters with low EIC receiving a single dose.     

CO2 relaxes parenchyma in the liquid-filled rat lung.

CO(2) regulation of lung compliance is currently explained by pH- and CO(2)-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation (Va) to perfusion (Q). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min(-1), 37 degrees C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O(2), balance N(2), and CO(2) varied to produce alveolar hypocapnia (Pco(2) = 26.1 +/- 2.4 mmHg, pH = 7.56 +/- 0.04) or hypercapnia (Pco(2) = 55.0 +/- 2.3 mmHg, pH = 7.23 +/- 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced approximately 30% when exposed to hypercapnia vs. hypocapnia (P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO(2) from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO(2) effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO(2), is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to Va/Q matching.